Wednesday, September 30, 2009

10/1 TE-RegenMed-StemCell feed

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Bioheart Makes Breakthrough in Cardiovascular Therapy with Stem Cells Obtained from Fat Tissue
September 30, 2009 at 5:39 pm


Cardiac stem cell trial seeks to treat some heart attack patients
September 30, 2009 at 5:39 pm


Teen attitudes toward smoking linked to likelihood of drinking and using drugs
September 30, 2009 at 2:14 pm


Celebrate Darwin's bicentennial by exploring how Darwin 'defined' evolutionary biology
September 30, 2009 at 2:14 pm


$16.8 million grant awarded to develop platelet recovery treatments
September 30, 2009 at 12:12 pm


Osiris Therapeutics to Present at Fourth Annual JMP Securities Healthcare Focus Conference
September 30, 2009 at 10:12 am


Article Published in Expert Opinion on Biological Therapy Evaluates StemEx(R) (carlecortemcel-l) for Leukemia and Lymphoma
September 30, 2009 at 8:17 am


The potential of biophotonic techniques in stem cell tracking and monitoring of tissue regeneration applied to cardiac stem cell therapy.
September 30, 2009 at 6:59 am

Related Articles

The potential of biophotonic techniques in stem cell tracking and monitoring of tissue regeneration applied to cardiac stem cell therapy.

J Biophotonics. 2009 Sep 28;

Authors: Wilson BC, Vitkin IA, Matthews DL

The use of injected stem cells, leading to regeneration of ischemic heart tissue, for example, following coronary artery occlusion, has emerged as a major new option for managing 'heart attack' patients. While some clinical trials have been encouraging, there have also been failures and there is little understanding of the multiplicity of factors that lead to the outcome. In this overview paper, the opportunities and challenges in applying biophotonic techniques to regenerative medicine, exemplified by the challenge of stem cell therapy of ischemic heart disease, are considered. The focus is on optical imaging to track stem cell distribution and fate, and optical spectroscopies and/or imaging to monitor the structural remodeling of the tissue and the resulting functional changes. The scientific, technological, and logistics issues involved in moving some of these techniques from pre-clinical research mode ultimately into the clinic are also highlighted. ((c) 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).

PMID: 19787683 [PubMed - as supplied by publisher]


Cardiomyocyte Differentiation of Human Induced Pluripotent Stem Cells.
September 30, 2009 at 6:59 am

Related Articles

Cardiomyocyte Differentiation of Human Induced Pluripotent Stem Cells.

Circulation. 2009 Sep 28;

Authors: Zwi L, Caspi O, Arbel G, Huber I, Gepstein A, Park IH, Gepstein L

BACKGROUND: -The ability to derive human induced pluripotent stem (hiPS) cell lines by reprogramming of adult fibroblasts with a set of transcription factors offers unique opportunities for basic and translational cardiovascular research. In the present study, we aimed to characterize the cardiomyocyte differentiation potential of hiPS cells and to study the molecular, structural, and functional properties of the generated hiPS-derived cardiomyocytes. Methods and Results-Cardiomyocyte differentiation of the hiPS cells was induced with the embryoid body differentiation system. Gene expression studies demonstrated that the cardiomyocyte differentiation process of the hiPS cells was characterized by an initial increase in mesoderm and cardiomesoderm markers, followed by expression of cardiac-specific transcription factors and finally by cardiac-specific structural genes. Cells in the contracting embryoid bodies were stained positively for cardiac troponin-I, sarcomeric alpha-actinin, and connexin-43. Reverse-transcription polymerase chain reaction studies demonstrated the expression of cardiac-specific sarcomeric proteins and ion channels. Multielectrode array recordings established the development of a functional syncytium with stable pacemaker activity and action potential propagation. Positive and negative chronotropic responses were induced by application of isoproterenol and carbamylcholine, respectively. Administration of quinidine, E4031 (IKr blocker), and chromanol 293B (IKs blocker) significantly affected repolarization, as manifested by prolongation of the local field potential duration. Conclusions-hiPS cells can differentiate into myocytes with cardiac-specific molecular, structural, and functional properties. These results, coupled with the potential of this technology to generate patient-specific hiPS lines, hold great promise for the development of in vitro models of cardiac genetic disorders, for drug discovery and testing, and for the emerging field of cardiovascular regenerative medicine.

PMID: 19786631 [PubMed - as supplied by publisher]


The collection and conservation in Italy of stem cells from umbilical cord blood.
September 30, 2009 at 6:59 am

Related Articles

The collection and conservation in Italy of stem cells from umbilical cord blood.

Med Law. 2009 Mar;28(2):387-400

Authors: Ricci G, Conti A, Paternoster M, Buccelli P

The blood contained in the umbilical cord offers a precious source of pluripotent stem cells, easily obtainable without invasive procedures, a source that, unlike embryonic stem cells, affords greater respect for ethical concerns. In relation to the therapeutic potential of these stem cells, personalized blood banks for newborns have been created and in various countries systems of research and cryoconservation of umbilical cord blood have been created, especially in private facilities. This facilitates promotion of the culture of donation and development of a network of umbilical cord blood sources, and spurs research to evaluate the real therapeutic potential of these cells. Italy has long prohibited management of umbilical cord blood in private form. Today, with new laws, Italy has achieved the indispensable legislative update in acknowledgment of social needs. Actually, the achieved system is solid autologous conservation. It guarantees to conserve a greater number of umbilical cords in public and private facilities.

PMID: 19705649 [PubMed - indexed for MEDLINE]


[Tissue engineering: a solution for organ replacement?]
September 30, 2009 at 6:59 am

Related Articles

[Tissue engineering: a solution for organ replacement?]

J Chir (Paris). 2009 Apr;146(2):109-11

Authors: Gaujoux S, Larghero J, Cattan P

PMID: 19523633 [PubMed - indexed for MEDLINE]


The potential of biophotonic techniques in stem cell tracking and monitoring of tissue regeneration applied to cardiac stem cell therapy.
September 30, 2009 at 6:40 am

Related Articles

The potential of biophotonic techniques in stem cell tracking and monitoring of tissue regeneration applied to cardiac stem cell therapy.

J Biophotonics. 2009 Sep 28;

Authors: Wilson BC, Vitkin IA, Matthews DL

The use of injected stem cells, leading to regeneration of ischemic heart tissue, for example, following coronary artery occlusion, has emerged as a major new option for managing 'heart attack' patients. While some clinical trials have been encouraging, there have also been failures and there is little understanding of the multiplicity of factors that lead to the outcome. In this overview paper, the opportunities and challenges in applying biophotonic techniques to regenerative medicine, exemplified by the challenge of stem cell therapy of ischemic heart disease, are considered. The focus is on optical imaging to track stem cell distribution and fate, and optical spectroscopies and/or imaging to monitor the structural remodeling of the tissue and the resulting functional changes. The scientific, technological, and logistics issues involved in moving some of these techniques from pre-clinical research mode ultimately into the clinic are also highlighted. ((c) 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).

PMID: 19787683 [PubMed - as supplied by publisher]


Modeling of flow-induced shear stress applied on 3D cellular scaffolds; Implications for vascular tissue-engineering.
September 30, 2009 at 6:24 am

Related Articles

Modeling of flow-induced shear stress applied on 3D cellular scaffolds; Implications for vascular tissue-engineering.

Biotechnol Bioeng. 2009 Sep 28;

Authors: Lesman A, Blinder Y, Levenberg S

Novel tissue-culture bioreactors employ flow-induced shear-stress as a means of mechanical stimulation of cells. We developed a computational fluid dynamics model of the complex 3D microstructure of a porous scaffold incubated in a direct perfusion bioreactor. Our model was designed to predict high shear-stress values within the physiological range of those naturally sensed by vascular cells (1-10 dyne/cm(2)), and will thereby provide suitable conditions for vascular tissue-engineering experiments. The model also accounts for cellular growth, which was designed as an added cell layer grown on all scaffold walls. Five model variants were designed, with geometric differences corresponding to cell-layer thicknesses of 0, 50, 75, 100 and 125 microm. Four inlet velocities (0.5, 1, 1.5 and 2 cm/sec) were applied to each model. Wall shear-stress distribution and overall pressure drop calculations were then used to characterize the relation between flow rate, shear stress, cell-layer thickness and pressure drop. The simulations showed that cellular growth within 3D scaffolds exposes cells to elevated shear stress, with considerably increasing average values in correlation to cell growth and inflow velocity. Our results provide in-depth analysis of the microdynamic environment of cells cultured within 3D environments, and thus provide advanced control over tissue development in-vitro. (c) 2009 Wiley Periodicals, Inc.

PMID: 19787638 [PubMed - as supplied by publisher]


Inverse engineering of medical devices made of bioresorbable polymers.
September 30, 2009 at 6:24 am

Related Articles

Inverse engineering of medical devices made of bioresorbable polymers.

Comput Methods Biomech Biomed Engin. 2009 Sep 21;:1

Authors: Huang R, Pan J

The degradation of medical devices made of bioresorbable polymers such as fixation devices in orthopaedic surgeries and scaffolds for tissue engineering can take from months to years. The trial and error approach of device development is therefore problematic and mathematical modelling of the biodegradation can help to accelerate the device development. This paper presents an inverse scheme to obtain the material parameters in a biodegradation model developed by Pan and his co-workers from existing experimental data of bioresorbable devices. The parameters can then be used to predict the degradation rate of new devices made of the same polymer. Firstly, the previously developed model is briefly outlined. Secondly, a finite element scheme and a time integration algorithm are developed for the direct analysis using the biodegradation model. Thirdly, an inverse analysis scheme is presented in combination with the direct analysis. Finally, several case studies of existing degradation data are presented to demonstrate the effectiveness of the inverse engineering approach.

PMID: 19787498 [PubMed - as supplied by publisher]


New methods to diagnose and treat cartilage degeneration.
September 30, 2009 at 6:24 am

Related Articles

New methods to diagnose and treat cartilage degeneration.

Nat Rev Rheumatol. 2009 Sep 29;

Authors: Daher RJ, Chahine NO, Greenberg AS, Sgaglione NA, Grande DA

Lesions in articular cartilage can result in significant musculoskeletal morbidity and display unique biomechanical characteristics that make repair difficult, at best. Several surgical procedures have been devised in an attempt to relieve pain, restore function, and delay or stop the progression of cartilaginous lesions. Advanced MRI and ultrasonography protocols are currently used in the evaluation of tissue repair and to improve diagnostic capability. Other nonoperative modalities, such as injection of intra-articular hyaluronic acid or supplementary oral glucosamine and chondroitin sulfate, have shown potential efficacy as anti-inflammatory and symptom-modifying agents. The emerging field of tissue engineering, involving the use of a biocompatible, structurally and mechanically stable scaffold, has shown promising early results in cartilage tissue repair. Scaffolds incorporating specific cell sources and bioactive molecules have been the focus in this new exciting field. Further work is required to better understand the behavior of chondrocytes and the variables that influence their ability to heal articular lesions. The future of cartilage repair will probably involve a combination of treatments in an attempt to achieve a regenerative tissue that is both biomechanically stable and, ideally, identical to the surrounding native tissues.

PMID: 19786989 [PubMed - as supplied by publisher]


Knockdown of angiotensinogen by shRNA-mediated RNA interference inhibits human visceral preadipocytes differentiation.
September 30, 2009 at 6:24 am

Related Articles

Knockdown of angiotensinogen by shRNA-mediated RNA interference inhibits human visceral preadipocytes differentiation.

Int J Obes (Lond). 2009 Sep 29;

Authors: Ye ZW, Wu XM, Jiang JG

Objective:The immediate cause of obesity is the massive deposition of subcutaneous and visceral fat attributing to the continuous proliferation and differentiation of preadipocytes. The identification of the underlying molecular mechanisms of preadipocytes differentiation is urgent, and will have an important role in plastic and reconstructive surgical procedures.Methods:Two small hairpin RNA (shRNA)-mediated RNA interference plasmids have been constructed on the basis of the activity of H1 promoter-driven expression vector psiRNA-hH1neo to suppress the expression of angiotensinogen (AGT) in human preadipocytes-visceral (HPA-v). Subsequently, glycerol-3-phosphate dehydrogenase (G3PDH) activity and intracytoplasmic lipids content were detected during the process of HPA-v differentiation.Results:Small hairpin RNA-expressing vectors have been successfully constructed to suppress the expression of AGT significantly. Both intracytoplasmic lipids content and G3PDH activity decreased to a certain extent compared with that in the control group in the whole process of HPA-v differentiation.Conclusions:Two shRNA-mediated AGT-targeting plasmids inhibited the process of HPA-v differentiation to a certain extent. However, the accumulation of intracytoplasmic lipids was not exclusively determined by the expression of AGT, and it may also be regulated by other factors. In conclusion, this study provided a method to inhibit the process of preadipocytes differentiation, and it may have a role in obesity treatment and adipose tissue engineering application.International Journal of Obesity advance online publication, 29 September 2009; doi:10.1038/ijo.2009.197.

PMID: 19786968 [PubMed - as supplied by publisher]


alpha-Fetoprotein as a modulator of the pro-inflammatory response of human keratinocytes.
September 30, 2009 at 6:24 am

Related Articles

alpha-Fetoprotein as a modulator of the pro-inflammatory response of human keratinocytes.

Br J Pharmacol. 2009 Sep 28;

Authors: Potapovich AI, Pastore S, Kostyuk VA, Lulli D, Mariani V, De Luca C, Dudich EI, Korkina LG

Background and purpose: The immunomodulatory effects of alpha-fetoprotein (AFP) on lymphocytes and macrophages have been described in vitro and in vivo. Recombinant forms of human AFP have been proposed as potential therapeutic entities for the treatment of autoimmune diseases. We examined the effects of embryonic and recombinant human AFP on the spontaneous, UVA- and cytokine-induced pro-inflammatory responses of human keratinocytes. Experimental approach: Cultures of primary and immortalized human keratinocytes (HaCaT) and human blood T lymphocytes were used. The effects of AFP on cytokine expression were studied by bioplexed elisa and quantitative reverse transcriptase polymerase chain reaction assay. Kinase and nuclear factor kappa B (NFkappaB) phosphorylation were quantified by intracellular elisa. Nuclear activator protein 1 and NFkappaB DNA binding activity was measured by specific assays. Nitric oxide and H(2)O(2) production and redox status were assessed by fluorescent probe and biochemical methods. Key results: All forms of AFP enhanced baseline expression of cytokines, chemokines and growth factors. AFP dose-dependently increased tumour necrosis factor alpha-stimulated granulocyte macrophage colony stimulating factor and interleukin 8 expression and decreased tumour necrosis factor alpha-induced monocyte chemotactic protein 1 and IP-10 (interferon gamma-produced protein of 10 kDa) expression. AFP induced a marked activator protein 1 activation in human keratinocytes. AFP also increased H(2)O(2) and modulated nitrite/nitrate levels in non-stimulated keratinocytes whereas it did not affect these parameters or cytokine release from UVA-stimulated cells. Phosphorylation of extracellular signal-regulated kinase (ERK1/2) and Akt1 but not NFkappaB was activated by AFP alone or by its combination with UVA. Conclusions and implications: Exogenous AFP induces activation of human keratinocytes, with de novo expression of a number of pro-inflammatory mediators and modulation of their pro-inflammatory response to cytokines or UVA. AFP may modulate inflammatory events in human skin.

PMID: 19785658 [PubMed - as supplied by publisher]


Shining light on a new class of hydrogels.
September 30, 2009 at 6:24 am

Related Articles

Shining light on a new class of hydrogels.

Nat Biotechnol. 2009 Jun;27(6):543-4

Authors: Jay SM, Saltzman WM

PMID: 19513057 [PubMed - indexed for MEDLINE]


Use of tissue-engineered skin to study in vitro biofilm development.
September 30, 2009 at 6:24 am

Related Articles

Use of tissue-engineered skin to study in vitro biofilm development.

Dermatol Surg. 2009 Sep;35(9):1334-41

Authors: Charles CA, Ricotti CA, Davis SC, Mertz PM, Kirsner RS

BACKGROUND: Biofilms are aggregations of microorganisms that have been identified as potential pathogens in the chronicity of nonhealing wounds. OBJECTIVE To develop an in vitro wound model to study biofilms using Graftskin, a tissue-engineered skin equivalent. MATERIALS AND METHODS: Graftskin constructs were divided into sections, and wounds were created on each section. Bacterial suspensions with a concentration of 10(6) CFU/mL were prepared from cultures of pathogenic isolates of Pseudomonas aeruginosa and Staphylococcus aureus. A 25-microL aliquot of each suspension was deposited in the center of wounds created on the Graftskin. Sections were incubated at various time points, and a biopsy was then taken from the wounded and inoculated area. Sections were visualized with light (hematoxylin and eosin) and epifluorescent microscopy (calcofluor white and ethidium bromide). RESULTS Biofilm was observed on the wound model. Biofilm formation was dependent on time of Graftskin exposure to the bacteria. Biofilm was visualized in the S. aureus group at an earlier time point than in the P. aeruginosa group. CONCLUSIONS: We demonstrated biofilm formation in vitro using a wound model. This model may provide a basis on which future studies may explore therapeutic modalities to prevent and eradicate pathogenic bacterial biofilm. The authors have indicated no significant interest with commercial supporters.

PMID: 19496791 [PubMed - indexed for MEDLINE]


Scientists discover clues to what makes human muscle age
September 30, 2009 at 1:16 am

 

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The potential of biophotonic techniques in stem cell tracking and monitoring of tissue regeneration applied to cardiac stem cell therapy.
September 30, 2009 at 9:53 am

Related Articles

The potential of biophotonic techniques in stem cell tracking and monitoring of tissue regeneration applied to cardiac stem cell therapy.

J Biophotonics. 2009 Sep 28;

Authors: Wilson BC, Vitkin IA, Matthews DL

The use of injected stem cells, leading to regeneration of ischemic heart tissue, for example, following coronary artery occlusion, has emerged as a major new option for managing 'heart attack' patients. While some clinical trials have been encouraging, there have also been failures and there is little understanding of the multiplicity of factors that lead to the outcome. In this overview paper, the opportunities and challenges in applying biophotonic techniques to regenerative medicine, exemplified by the challenge of stem cell therapy of ischemic heart disease, are considered. The focus is on optical imaging to track stem cell distribution and fate, and optical spectroscopies and/or imaging to monitor the structural remodeling of the tissue and the resulting functional changes. The scientific, technological, and logistics issues involved in moving some of these techniques from pre-clinical research mode ultimately into the clinic are also highlighted. ((c) 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).

PMID: 19787683 [PubMed - as supplied by publisher]


Modeling of flow-induced shear stress applied on 3D cellular scaffolds; Implications for vascular tissue-engineering.
September 30, 2009 at 9:53 am

Related Articles

Modeling of flow-induced shear stress applied on 3D cellular scaffolds; Implications for vascular tissue-engineering.

Biotechnol Bioeng. 2009 Sep 28;

Authors: Lesman A, Blinder Y, Levenberg S

Novel tissue-culture bioreactors employ flow-induced shear-stress as a means of mechanical stimulation of cells. We developed a computational fluid dynamics model of the complex 3D microstructure of a porous scaffold incubated in a direct perfusion bioreactor. Our model was designed to predict high shear-stress values within the physiological range of those naturally sensed by vascular cells (1-10 dyne/cm(2)), and will thereby provide suitable conditions for vascular tissue-engineering experiments. The model also accounts for cellular growth, which was designed as an added cell layer grown on all scaffold walls. Five model variants were designed, with geometric differences corresponding to cell-layer thicknesses of 0, 50, 75, 100 and 125 microm. Four inlet velocities (0.5, 1, 1.5 and 2 cm/sec) were applied to each model. Wall shear-stress distribution and overall pressure drop calculations were then used to characterize the relation between flow rate, shear stress, cell-layer thickness and pressure drop. The simulations showed that cellular growth within 3D scaffolds exposes cells to elevated shear stress, with considerably increasing average values in correlation to cell growth and inflow velocity. Our results provide in-depth analysis of the microdynamic environment of cells cultured within 3D environments, and thus provide advanced control over tissue development in-vitro. (c) 2009 Wiley Periodicals, Inc.

PMID: 19787638 [PubMed - as supplied by publisher]


Inverse engineering of medical devices made of bioresorbable polymers.
September 30, 2009 at 9:53 am

Related Articles

Inverse engineering of medical devices made of bioresorbable polymers.

Comput Methods Biomech Biomed Engin. 2009 Sep 21;:1

Authors: Huang R, Pan J

The degradation of medical devices made of bioresorbable polymers such as fixation devices in orthopaedic surgeries and scaffolds for tissue engineering can take from months to years. The trial and error approach of device development is therefore problematic and mathematical modelling of the biodegradation can help to accelerate the device development. This paper presents an inverse scheme to obtain the material parameters in a biodegradation model developed by Pan and his co-workers from existing experimental data of bioresorbable devices. The parameters can then be used to predict the degradation rate of new devices made of the same polymer. Firstly, the previously developed model is briefly outlined. Secondly, a finite element scheme and a time integration algorithm are developed for the direct analysis using the biodegradation model. Thirdly, an inverse analysis scheme is presented in combination with the direct analysis. Finally, several case studies of existing degradation data are presented to demonstrate the effectiveness of the inverse engineering approach.

PMID: 19787498 [PubMed - as supplied by publisher]


New methods to diagnose and treat cartilage degeneration.
September 30, 2009 at 9:53 am

Related Articles

New methods to diagnose and treat cartilage degeneration.

Nat Rev Rheumatol. 2009 Sep 29;

Authors: Daher RJ, Chahine NO, Greenberg AS, Sgaglione NA, Grande DA

Lesions in articular cartilage can result in significant musculoskeletal morbidity and display unique biomechanical characteristics that make repair difficult, at best. Several surgical procedures have been devised in an attempt to relieve pain, restore function, and delay or stop the progression of cartilaginous lesions. Advanced MRI and ultrasonography protocols are currently used in the evaluation of tissue repair and to improve diagnostic capability. Other nonoperative modalities, such as injection of intra-articular hyaluronic acid or supplementary oral glucosamine and chondroitin sulfate, have shown potential efficacy as anti-inflammatory and symptom-modifying agents. The emerging field of tissue engineering, involving the use of a biocompatible, structurally and mechanically stable scaffold, has shown promising early results in cartilage tissue repair. Scaffolds incorporating specific cell sources and bioactive molecules have been the focus in this new exciting field. Further work is required to better understand the behavior of chondrocytes and the variables that influence their ability to heal articular lesions. The future of cartilage repair will probably involve a combination of treatments in an attempt to achieve a regenerative tissue that is both biomechanically stable and, ideally, identical to the surrounding native tissues.

PMID: 19786989 [PubMed - as supplied by publisher]


Knockdown of angiotensinogen by shRNA-mediated RNA interference inhibits human visceral preadipocytes differentiation.
September 30, 2009 at 9:53 am

Related Articles

Knockdown of angiotensinogen by shRNA-mediated RNA interference inhibits human visceral preadipocytes differentiation.

Int J Obes (Lond). 2009 Sep 29;

Authors: Ye ZW, Wu XM, Jiang JG

Objective:The immediate cause of obesity is the massive deposition of subcutaneous and visceral fat attributing to the continuous proliferation and differentiation of preadipocytes. The identification of the underlying molecular mechanisms of preadipocytes differentiation is urgent, and will have an important role in plastic and reconstructive surgical procedures.Methods:Two small hairpin RNA (shRNA)-mediated RNA interference plasmids have been constructed on the basis of the activity of H1 promoter-driven expression vector psiRNA-hH1neo to suppress the expression of angiotensinogen (AGT) in human preadipocytes-visceral (HPA-v). Subsequently, glycerol-3-phosphate dehydrogenase (G3PDH) activity and intracytoplasmic lipids content were detected during the process of HPA-v differentiation.Results:Small hairpin RNA-expressing vectors have been successfully constructed to suppress the expression of AGT significantly. Both intracytoplasmic lipids content and G3PDH activity decreased to a certain extent compared with that in the control group in the whole process of HPA-v differentiation.Conclusions:Two shRNA-mediated AGT-targeting plasmids inhibited the process of HPA-v differentiation to a certain extent. However, the accumulation of intracytoplasmic lipids was not exclusively determined by the expression of AGT, and it may also be regulated by other factors. In conclusion, this study provided a method to inhibit the process of preadipocytes differentiation, and it may have a role in obesity treatment and adipose tissue engineering application.International Journal of Obesity advance online publication, 29 September 2009; doi:10.1038/ijo.2009.197.

PMID: 19786968 [PubMed - as supplied by publisher]


Cardiomyocyte Differentiation of Human Induced Pluripotent Stem Cells.
September 30, 2009 at 9:53 am

Related Articles

Cardiomyocyte Differentiation of Human Induced Pluripotent Stem Cells.

Circulation. 2009 Sep 28;

Authors: Zwi L, Caspi O, Arbel G, Huber I, Gepstein A, Park IH, Gepstein L

BACKGROUND: -The ability to derive human induced pluripotent stem (hiPS) cell lines by reprogramming of adult fibroblasts with a set of transcription factors offers unique opportunities for basic and translational cardiovascular research. In the present study, we aimed to characterize the cardiomyocyte differentiation potential of hiPS cells and to study the molecular, structural, and functional properties of the generated hiPS-derived cardiomyocytes. Methods and Results-Cardiomyocyte differentiation of the hiPS cells was induced with the embryoid body differentiation system. Gene expression studies demonstrated that the cardiomyocyte differentiation process of the hiPS cells was characterized by an initial increase in mesoderm and cardiomesoderm markers, followed by expression of cardiac-specific transcription factors and finally by cardiac-specific structural genes. Cells in the contracting embryoid bodies were stained positively for cardiac troponin-I, sarcomeric alpha-actinin, and connexin-43. Reverse-transcription polymerase chain reaction studies demonstrated the expression of cardiac-specific sarcomeric proteins and ion channels. Multielectrode array recordings established the development of a functional syncytium with stable pacemaker activity and action potential propagation. Positive and negative chronotropic responses were induced by application of isoproterenol and carbamylcholine, respectively. Administration of quinidine, E4031 (IKr blocker), and chromanol 293B (IKs blocker) significantly affected repolarization, as manifested by prolongation of the local field potential duration. Conclusions-hiPS cells can differentiate into myocytes with cardiac-specific molecular, structural, and functional properties. These results, coupled with the potential of this technology to generate patient-specific hiPS lines, hold great promise for the development of in vitro models of cardiac genetic disorders, for drug discovery and testing, and for the emerging field of cardiovascular regenerative medicine.

PMID: 19786631 [PubMed - as supplied by publisher]


alpha-Fetoprotein as a modulator of the pro-inflammatory response of human keratinocytes.
September 30, 2009 at 9:53 am

Related Articles

alpha-Fetoprotein as a modulator of the pro-inflammatory response of human keratinocytes.

Br J Pharmacol. 2009 Sep 28;

Authors: Potapovich AI, Pastore S, Kostyuk VA, Lulli D, Mariani V, De Luca C, Dudich EI, Korkina LG

Background and purpose: The immunomodulatory effects of alpha-fetoprotein (AFP) on lymphocytes and macrophages have been described in vitro and in vivo. Recombinant forms of human AFP have been proposed as potential therapeutic entities for the treatment of autoimmune diseases. We examined the effects of embryonic and recombinant human AFP on the spontaneous, UVA- and cytokine-induced pro-inflammatory responses of human keratinocytes. Experimental approach: Cultures of primary and immortalized human keratinocytes (HaCaT) and human blood T lymphocytes were used. The effects of AFP on cytokine expression were studied by bioplexed elisa and quantitative reverse transcriptase polymerase chain reaction assay. Kinase and nuclear factor kappa B (NFkappaB) phosphorylation were quantified by intracellular elisa. Nuclear activator protein 1 and NFkappaB DNA binding activity was measured by specific assays. Nitric oxide and H(2)O(2) production and redox status were assessed by fluorescent probe and biochemical methods. Key results: All forms of AFP enhanced baseline expression of cytokines, chemokines and growth factors. AFP dose-dependently increased tumour necrosis factor alpha-stimulated granulocyte macrophage colony stimulating factor and interleukin 8 expression and decreased tumour necrosis factor alpha-induced monocyte chemotactic protein 1 and IP-10 (interferon gamma-produced protein of 10 kDa) expression. AFP induced a marked activator protein 1 activation in human keratinocytes. AFP also increased H(2)O(2) and modulated nitrite/nitrate levels in non-stimulated keratinocytes whereas it did not affect these parameters or cytokine release from UVA-stimulated cells. Phosphorylation of extracellular signal-regulated kinase (ERK1/2) and Akt1 but not NFkappaB was activated by AFP alone or by its combination with UVA. Conclusions and implications: Exogenous AFP induces activation of human keratinocytes, with de novo expression of a number of pro-inflammatory mediators and modulation of their pro-inflammatory response to cytokines or UVA. AFP may modulate inflammatory events in human skin.

PMID: 19785658 [PubMed - as supplied by publisher]


The collection and conservation in Italy of stem cells from umbilical cord blood.
September 30, 2009 at 9:53 am

Related Articles

The collection and conservation in Italy of stem cells from umbilical cord blood.

Med Law. 2009 Mar;28(2):387-400

Authors: Ricci G, Conti A, Paternoster M, Buccelli P

The blood contained in the umbilical cord offers a precious source of pluripotent stem cells, easily obtainable without invasive procedures, a source that, unlike embryonic stem cells, affords greater respect for ethical concerns. In relation to the therapeutic potential of these stem cells, personalized blood banks for newborns have been created and in various countries systems of research and cryoconservation of umbilical cord blood have been created, especially in private facilities. This facilitates promotion of the culture of donation and development of a network of umbilical cord blood sources, and spurs research to evaluate the real therapeutic potential of these cells. Italy has long prohibited management of umbilical cord blood in private form. Today, with new laws, Italy has achieved the indispensable legislative update in acknowledgment of social needs. Actually, the achieved system is solid autologous conservation. It guarantees to conserve a greater number of umbilical cords in public and private facilities.

PMID: 19705649 [PubMed - indexed for MEDLINE]


Shining light on a new class of hydrogels.
September 30, 2009 at 9:53 am

Related Articles

Shining light on a new class of hydrogels.

Nat Biotechnol. 2009 Jun;27(6):543-4

Authors: Jay SM, Saltzman WM

PMID: 19513057 [PubMed - indexed for MEDLINE]


Use of tissue-engineered skin to study in vitro biofilm development.
September 30, 2009 at 9:53 am

Related Articles

Use of tissue-engineered skin to study in vitro biofilm development.

Dermatol Surg. 2009 Sep;35(9):1334-41

Authors: Charles CA, Ricotti CA, Davis SC, Mertz PM, Kirsner RS

BACKGROUND: Biofilms are aggregations of microorganisms that have been identified as potential pathogens in the chronicity of nonhealing wounds. OBJECTIVE To develop an in vitro wound model to study biofilms using Graftskin, a tissue-engineered skin equivalent. MATERIALS AND METHODS: Graftskin constructs were divided into sections, and wounds were created on each section. Bacterial suspensions with a concentration of 10(6) CFU/mL were prepared from cultures of pathogenic isolates of Pseudomonas aeruginosa and Staphylococcus aureus. A 25-microL aliquot of each suspension was deposited in the center of wounds created on the Graftskin. Sections were incubated at various time points, and a biopsy was then taken from the wounded and inoculated area. Sections were visualized with light (hematoxylin and eosin) and epifluorescent microscopy (calcofluor white and ethidium bromide). RESULTS Biofilm was observed on the wound model. Biofilm formation was dependent on time of Graftskin exposure to the bacteria. Biofilm was visualized in the S. aureus group at an earlier time point than in the P. aeruginosa group. CONCLUSIONS: We demonstrated biofilm formation in vitro using a wound model. This model may provide a basis on which future studies may explore therapeutic modalities to prevent and eradicate pathogenic bacterial biofilm. The authors have indicated no significant interest with commercial supporters.

PMID: 19496791 [PubMed - indexed for MEDLINE]

 

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Tuesday, September 29, 2009

9/30 TE-RegenMed-StemCell feed

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Stem cell success points to way to regenerate parathyroid glands
September 29, 2009 at 5:09 pm


Telltale moss
September 29, 2009 at 1:08 pm


Pluristem Therapeutics Has Been Selected to Present at The Israeli Presidential Conference 2009: Facing Tomorrow, Based on the Company's Proprietary Technology and the Potential to Shape The Future of the Stem Cell Industry
September 29, 2009 at 11:08 am


Allogenic stem cell therapy improves right ventricular function by improving lung pathology in rats with pulmonary hypertension.
September 29, 2009 at 8:49 am

Related Articles

Allogenic stem cell therapy improves right ventricular function by improving lung pathology in rats with pulmonary hypertension.

Am J Physiol Heart Circ Physiol. 2009 Sep 25;

Authors: Umar S, de Visser YP, Steendijk P, Schutte CI, Laghmani EH, Wagenaar GT, Bax WH, Mantikou E, Pijnappels DA, Atsma DE, Schalij MJ, van der Wall EE, van der Laarse A

Pulmonary arterial hypertension (PAH) is a chronic lung disease that leads to right ventricular hypertrophy (RVH), remodeling and failure. We tested treatment with bone marrow-derived mesenchymal stem cells (MSCs) obtained from donor rats with monocrotaline (MCT)-induced PAH to recipient rats with MCT-induced PAH on pulmonary artery pressure, lung pathology and RV function. This model was chosen to mimic autologous MSC therapy. At day 1, PAH was induced by MCT (60 mg/kg) in 20 female Wistar rats. At day 14, rats were treated with 10(6) MSCs i.v. (MCT+MSC) or saline (MCT60). MSCs were obtained from donor rats with PAH at 28 days after MCT. A control group received saline at days 1 and 14. At day 28 RV function of recipient rats was assessed, followed by isolation of lungs and heart. RVH was quantified by weight ratio of RV/(LV+interventricular septum). MCT induced an increase of RV peak pressure from 27+/-5 to 42+/-17 mmHg, RVH (from 0.25+/-0.04 to 0.47+/-0.12), depressed RV ejection fraction (RVEF) (from 56+/-11 to 43+/-6%) and increased lung weight (from 0.96+/-0.15 to 1.66+/-0.32 g) including thickening of arteriolar walls and alveolar septa. MSC treatment attenuated PAH (31+/-4 mmHg), RVH (0.32+/-0.07), normalized RVEF (52+/-5%), reduced lung weight (1.16+/-0.24 g) and inhibited thickening of arterioles and alveolar septa. We conclude that application of MSCs from donor rats with PAH reduces RV pressure overload, RV dysfunction, and lung pathology in recipient rats with PAH. These results suggest that autologous MSC therapy may alleviate cardiac and pulmonary symptoms in PAH patients. Key words: stem cells, pulmonary arterial hypertension, heart failure, hypertrophy.

PMID: 19783775 [PubMed - as supplied by publisher]


Effects of Granulocyte Colony-Stimulating Factor on the Proliferation and Cell-Fate Specification of Neural Stem Cells.
September 29, 2009 at 8:49 am

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Effects of Granulocyte Colony-Stimulating Factor on the Proliferation and Cell-Fate Specification of Neural Stem Cells.

Neuroscience. 2009 Sep 24;

Authors: Liu H, Jia D, Fu J, Zhao S, He G, Ling EA, Gao J, Hao A

Granulocyte-colony stimulating factor is a growth factor that regulates proliferation, differentiation and survival of hematopoietic progenitor cells. There is growing evidence to suggest that G-CSF exerts a powerful neuroprotective effect in different neurological disorders. However, it has remained to be elucidated if G-CSF has a direct effect on neural stem cells (NSCs). Here, we show that G-CSF could stimulate the proliferation of NSCs and promote their differentiation in vitro. Additionally, we have shown that G-CSF-induced proliferation of NSCs is associated with phosphorylation of STAT3, and the differentiation is linked to altered expression of differentiation-related genes. Remarkably, G-CSF could not initiate the differentiation of NSCs. The added roles of G-CSF in regulating proliferation and differentiation of NSCs as shown in this study would serve as a useful reference in designing new stem cell therapy strategies for promoting brain recovery and repair.

PMID: 19782730 [PubMed - as supplied by publisher]


Early lineage specification of long-lived germline precursors in the colonial ascidian Botryllus schlosseri.
September 29, 2009 at 7:00 am

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Early lineage specification of long-lived germline precursors in the colonial ascidian Botryllus schlosseri.

Development. 2009 Oct;136(20):3485-94

Authors: Brown FD, Tiozzo S, Roux MM, Ishizuka K, Swalla BJ, De Tomaso AW

In many taxa, germline precursors segregate from somatic lineages during embryonic development and are irreversibly committed to gametogenesis. However, in animals that can propagate asexually, germline precursors can originate in adults. Botryllus schlosseri is a colonial ascidian that grows by asexual reproduction, and on a weekly basis regenerates all somatic and germline tissues. Embryonic development in solitary ascidians is the classic example of determinative specification, and we are interested in both the origins and the persistence of stem cells responsible for asexual development in colonial ascidians. In this study, we characterized vasa as a putative marker of germline precursors. We found that maternally deposited vasa mRNA segregates early in development to a posterior lineage of cells, suggesting that germline formation is determinative in colonial ascidians. In adults, vasa expression was observed in the gonads, as well as in a population of mobile cells scattered throughout the open circulatory system, consistent with previous transplantation/reconstitution results. vasa expression was dynamic during asexual development in both fertile and infertile adults, and was also enriched in a population of stem cells. Germline precursors in juveniles could contribute to gamete formation immediately upon transplantation into fertile adults, thus vasa expression is correlated with the potential for gamete formation, which suggests that it is a marker for embryonically specified, long-lived germline progenitors. Transient vasa knockdown did not have obvious effects on germline or somatic development in adult colonies, although it did result in a profound heterochrony, suggesting that vasa might play a homeostatic role in asexual development.

PMID: 19783737 [PubMed - in process]


Regenerative medicine: A primer for paediatricians.
September 29, 2009 at 7:00 am

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Regenerative medicine: A primer for paediatricians.

Early Hum Dev. 2009 Sep 25;

Authors: Polak DJ

Regenerative medicine is a multidisciplinary field concerned with the replacement, repair or restoration of injured tissues. Cell therapy and tissue engineering are part of the broader remit of regenerative medicine. The ultimate aim is to provide safe and efficient therapies for a large number of clinical conditions. Novel regenerative therapies are already in use in initial clinical trials. The main components of regenerative medicine are cells and specially designed materials. A vast variety of cells types are currently used including: adult and stem cells. Equally a large number of natural and man-made materials have been investigated. Despite of considerable advances many challenges lie ahead. These are summarised in this review article. The field is slowly maturing and the initial unhelpful hype has been replaced by a more measured, mature and realistic outlook.

PMID: 19783108 [PubMed - as supplied by publisher]


Tissue-engineered skin substitutes in regenerative medicine.
September 29, 2009 at 7:00 am

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Tissue-engineered skin substitutes in regenerative medicine.

Curr Opin Biotechnol. 2009 Sep 24;

Authors: Mansbridge J

Recent advance in cellular tissue-engineered skin constructs have refined the applications already commercially available, in particular, by the use of genetically modified cells to enhance their properties on the treatment of wounds and to ease the application of epidermis using sprayed keratinocytes. This approach lends itself to use of chimeric epidermis, cultured allogeneic cells, to provide short-term coverage, together with minimally cultured autologous cells for long-term repair. Experimental models of skin include pathological conditions, phenomena such as aging and organogenesis, as in the hair follicle grown from isolated cells in vitro. The recent development of induced pluripotent stem cells raises the possibility of realizing the dream of skin and even limb regeneration shown by animals such as the salamander.

PMID: 19782559 [PubMed - as supplied by publisher]


On the effect of substrate curvature on cell mechanics.
September 29, 2009 at 7:00 am

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On the effect of substrate curvature on cell mechanics.

Biomaterials. 2009 Sep 23;

Authors: Sanz-Herrera JA, Moreo P, García-Aznar JM, Doblaré M

Cell movement on a substrate or within the extracellular matrix is the phenomenological response to a biochemical signals' cascade transcripted into biophysical processes and viceversa. The process is complex in nature, including different length scales from the whole cell to organelle and protein levels, where substrate/ECM curvature has been shown to play an important role on cell's behavior. From a macroscopic perspective, the cytoskeleton may be modeled as a continuum body unbalanced by internal protein motors. In this work, we propose a cell constitutive model to simulate cell attachment on curved substrates, activated by contractile forces. We first analyze a single fiber bundle composed by microtubules, actin filaments and myosin machinery. Then, the model is macroscopically extended to the cytoskeletal level using homogenization. Substrate curvature has two implications in our model: (i) it forces fibers to work in a curved (bent) position and (ii) it eventually creates a pre-deformation state in the cytoskeleton. Interestingly, the model shows higher contractile force inhibition as curvature increases when implemented over different substrate morphologies, being this consistent with experimental results. The presented model may result useful in many new regenerative medicine techniques, miniaturized experimental tests, or to analyze cell behavior on manufactured nanoscaffolds for tissue engineering.

PMID: 19781764 [PubMed - as supplied by publisher]


Repair of left ventricular aneurysm: ten-year experience in Chinese patients.
September 29, 2009 at 7:00 am

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Repair of left ventricular aneurysm: ten-year experience in Chinese patients.

Chin Med J (Engl). 2009 Sep 5;122(17):1963-8

Authors: Fan HG, Zheng Z, Feng W, Yuan X, Wang W, Hu SS

BACKGROUND: A large transmural myocardial infarction often results in a dyskinetic or akinetic left ventricular aneurysm (LVA). This study aimed to explore the early and long-term clinical outcomes and to identify predictors for survivals and hospital re-admission after the repair of left ventricular aneurysm. METHODS: We followed up 497 patients who had undergone LVA repair from a single center in China between 1995 and 2005. The perioperative parameters were recorded. Risk factors for early mortality and long-term results were analyzed by multivariate Logistic regression. Cox's proportional hazard model was used to calculate risk factors for major adverse cardiac and cerebrovascular events, cause of death and re-admission. Kaplan-Meier curve was employed to analyze long-term survival. RESULTS: The operative mortality was 2.0%. The long-term mortality was 11.1% and cardiac causes contributed to 61.8% of the overall long-term mortality. Four hundred and thirty-two patients survived during the follow-up period and 37.5% of them had been re-admitted at least one time. One hundred and five patients experienced major adverse cardiac and cerebrovascular events. Survival analysis exhibited that the probability of survival at 1 and 5 years after operation was 96% and 86% respectively. Previous atrial fibrillation was the independent risk factor for early mortality. Independent risk factors for long-term mortality were poor left ventricular ejection fraction and stroke,and risk factors for cardiac mortality were intraventricular block, stroke and poor left ventricular ejection fraction. Stroke, intraventricular block and advanced age were independent risk factors for major adverse cardiac and cerebrovascular events, and New York Heart Association (NYHA) class III-IV was the only risk factor for hospital re-admission. CONCLUSIONS: Postinfarction LVA can be repaired and satisfying early and long-term clinical outcome can be obtained. Endoventricular circular plasty technique is the better choice than linear repair in patients with large LVA. Survival is affected in patients with poor heart function, intraventricular block and stroke.

PMID: 19781378 [PubMed - in process]


[The Chinese coronary artery bypass grafting registry report: 2004-2005.]
September 29, 2009 at 7:00 am

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[The Chinese coronary artery bypass grafting registry report: 2004-2005.]

Zhonghua Xin Xue Guan Bing Za Zhi. 2009 Mar;37(3):240-243

Authors: , Hu SS

OBJECTIVE: Number of coronary artery bypass grafting (CABG) increased steadily during the past decade as a result of a higher incidence of coronary artery disease in China. However, little is known about the current status of CABG surgery in contemporary China. This study was to get exact information on CABG in China. METHODS: A national multicentre database of patients undergoing CABG with the name of the Chinese CABG Registry Study was established at Fuwai hospital, Beijing, China which is the biggest cardiac centre of China in 2006 and 32 centers of cardiac surgery all over China (mainland) participated in the study. Registry forms were used to collect related information of patients undergoing CABG in these centers for statistical analysis. RESULTS: From January 2004 to December 2005, CABG was performed in 9247 consecutive patients with coronary artery disease. Mean age was (62.1 +/- 9.1) years and 21.5% patients were female, 76.7% patients had triple vessel disease, and 25.8% patients had left main disease. Overall in-hospital mortality was 3.3%. The in-hospital mortality of isolated CABG was 2.2%. CONCLUSION: The in-hospital mortality and the incidences of major accidents of surgery were low in these patients underwent CABG. The operative risk evaluating system for the Chinese CABG patients should be established to improve the survival of CABG operation in China.

PMID: 19781149 [PubMed - as supplied by publisher]


Responses of adipose-derived stem cells during hypoxia: enhanced skin-regenerative potential.
September 29, 2009 at 6:49 am

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Responses of adipose-derived stem cells during hypoxia: enhanced skin-regenerative potential.

Expert Opin Biol Ther. 2009 Sep 28;

Authors: Chung HM, Won CH, Sung JH

Mesenchymal stem cells within the stromal-vascular fraction of subcutaneous adipose tissue (i.e., adipose-derived stem cells (ASCs)), have been used for tissue engineering. In addition to serving a building-block function, ASCs are reported to secrete growth factors that are essential for their function. Increasing evidence indicates that ASCs play a significant role in skin regeneration, a function that is enhanced by hypoxia through upregulating secretion of growth factors. Although the anatomical sites of ASCs in the body are relatively oxygen-deficient, ASCs are usually cultured under normoxic conditions (i.e., atmospheric oxygen levels). Culturing ASCs under physiologically relevant low-oxygen-tension conditions may uniquely benefit the expansion, differentiation, adhesion, growth factor secretion and regenerative potential of ASCs. Therefore, understanding the response and adaptation of ASCs to hypoxia may be invaluable for developing novel cell- and cyto-therapy strategies. This review highlights our current understanding of cellular and molecular responses of ASCs to hypoxia, focusing on the enhancement of ASC function and secretory activity by hypoxic culture conditions.

PMID: 19780713 [PubMed - as supplied by publisher]


Hemangioblastic characteristics of human adipose tissue-derived adult stem cells in vivo.
September 29, 2009 at 6:49 am

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Hemangioblastic characteristics of human adipose tissue-derived adult stem cells in vivo.

Arch Med Res. 2009 May;40(4):311-7

Authors: Fang B, Luo S, Song Y, Li N, Cao Y

Recent studies have demonstrated the existence of a population of adipose tissue-derived adult stem (ADAS) cells that can undergo multilineage differentiation in vitro. However, it remains unclear whether these cells maintain their multilineage potential in vivo. The aim of this study was to investigate whether Flk1(+)CD31(-)CD34(-) ADAS cells have characteristics of hemangioblasts. These human ADAS (hADAS) cells were able to differentiate into endothelial and hematopoietic cells at the single-cell level in vivo. These postnatal Flk1(+)CD31(-)CD34(-) hADAS cells bear characteristics of hemangioblast and may have potential application for the hematopoietic and vascular diseases.

PMID: 19608022 [PubMed - indexed for MEDLINE]


Centrifugal seeding of mammalian cells in nonwoven fibrous matrices.
September 29, 2009 at 6:18 am

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Centrifugal seeding of mammalian cells in nonwoven fibrous matrices.

Biotechnol Prog. 2009 Sep 25;

Authors: Ng R, Gurm JS, Yang ST

Three-dimensional (3D) cell cultures have many advantages over two-dimensional cultures. However, seeding cells in 3D scaffolds such as nonwoven fibrous polyethylene terephthalate (PET) matrices has been a challenge task in tissue engineering and cell culture bioprocessing. In this study, a centrifugal seeding method was investigated to improve the cell seeding efficiency in PET matrices with two different porosities (93% and 88%). Both the centrifugal force and centrifugation time were found to affect the seeding efficiency. With an appropriate centrifugation speed, a high 80-90% cell seeding efficiency was achieved and the time to reach this high seeding efficiency was less than 5 min. The seeding efficiency was similar for matrices with different porosities, although the optimal seeding time was significantly shorter for the low-porosity scaffold. Post seeding cell viability was demonstrated by culturing colon cancer cells seeded in PET matrices for over 5 days. The centrifugal seeding method developed in this work can be used to efficiently and uniformly seed small fibrous scaffolds for applications in 3D cell-based assays for high-throughput screening. (c) 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009.

PMID: 19785042 [PubMed - as supplied by publisher]


Fabrication and biocompatibility of nano non-stoichiometric apatite and poly(epsilon-caprolactone) composite scaffold by using prototyping controlled process.
September 29, 2009 at 6:18 am

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Fabrication and biocompatibility of nano non-stoichiometric apatite and poly(epsilon-caprolactone) composite scaffold by using prototyping controlled process.

J Mater Sci Mater Med. 2009 Sep 27;

Authors: Ye L, Zeng X, Li H, Ai Y

Nano biocomposite scaffolds of non-stoichiometric apatite (ns-AP) and poly(epsilon-caprolactone) (PCL) were prepared by a prototyping controlled process (PCP). The results show that the composite scaffolds with 40 wt% ns-AP contained open and well interconnected pores with a size of 400-500 mum, and exhibited a maximum porosity of 76%. The ns-AP particles were not completely embedded in PCL matrix while exposed on the composite surface, which might be useful for cell attachment and growth. Proliferation of MG(63) cells was significantly better on the composite scaffolds with porosity of 76% than that those with porosity of 53%, indicating that the scaffolds with high porosity facilitated cell growth, and could promote cell proliferation. The composite scaffolds were implanted into rabbit thighbone defects to investigate the in vivo biocompatibility and osteogenesis. Radiological and histological examination confirmed that the new bony tissue had grown easily into the entire composite scaffold. The results suggest that the well-interconnected pores in the scaffolds might encourage cell proliferation, and migration to stimulate cell functions, thus enhancing bone formation in the scaffolds. This study shows that bioactive and biocompatible ns-AP/PCL composite scaffolds have potential applications in bone tissue engineering.

PMID: 19784867 [PubMed - as supplied by publisher]


Interaction between hepatocytes and collagen gel in hollow fibers.
September 29, 2009 at 6:18 am

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Interaction between hepatocytes and collagen gel in hollow fibers.

Cytotechnology. 2009 Sep 27;

Authors: Dai J, Zhang GL, Meng Q

Gel entrapment culture of primary mammalian cells within collagen gel is one important configuration for construction of bioartificial organ as well as in vitro model for predicting drug situation in vivo. Gel contraction in entrapment culture, resulting from cell-mediated reorganization of the extracellular matrix, was commonly used to estimate cell viability. However, the exact influence of gel contraction on cell activities has rarely been addressed. This paper investigated the gel contraction under varying culture conditions and its effect on the activities of rat hepatocyte entrapped in collagen gel within hollow fibers. The hepatocyte activities were reflected by cell viability together with liver-specific functions on urea secretion and cytochrome P450 2E1. Unexpectedly, no gel contraction occurred during gel entrapment culture of hepatocyte under a high collagen concentration, but hepatocytes still maintained cell viability and liver-specific functions at a similar level to the other cultures with normal gel contraction. It seems that cell activities are unassociated with gel contraction. Alternatively, the mass transfer resistance induced by the combined effect of collagen concentration, gel contraction and cell density could be a side effect to reduce cell activities. The findings with gel entrapment culture of hepatocytes would be also informative for the other cell culture targeting pathological studies and tissue engineering.

PMID: 19784829 [PubMed - as supplied by publisher]


Increased oral fibroblast lifespan is telomerase-independent.
September 29, 2009 at 6:18 am

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Increased oral fibroblast lifespan is telomerase-independent.

J Dent Res. 2009 Oct;88(10):916-21

Authors: Enoch S, Wall I, Peake M, Davies L, Farrier J, Giles P, Baird D, Kipling D, Price P, Moseley R, Thomas D, Stephens P

Oral mucosal wound-healing is characterized by rapid re-epithelialization and remodeling, with minimal scar formation. This may be attributed to the distinct phenotypic characteristics of the resident fibroblasts. To test this hypothesis, we investigated patient-matched oral mucosal and skin fibroblasts. Compared with skin fibroblasts, oral mucosal fibroblasts had longer proliferative lifespans, underwent more population doublings, and experienced senescence later, which was directly related to longer telomere lengths within oral mucosal fibroblasts. The presence of these longer telomeres was independent of telomerase expression, since both oral oral mucosal fibroblasts and skin fibroblasts were negative for active telomerase, as assessed according to the Telomeric Repeat Amplification Protocol. This study has demonstrated that, compared with skin fibroblasts, oral mucosal fibroblasts are 'younger', with a more embryonic/fetal-like phenotype that may provide a notable advantage for their ability to repair wounds in a scarless fashion.

PMID: 19783799 [PubMed - in process]


Films based on human hair keratin as substrates for cell culture and tissue engineering.
September 29, 2009 at 6:18 am

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Films based on human hair keratin as substrates for cell culture and tissue engineering.

Biomaterials. 2009 Sep 22;

Authors: Reichl S

Keratin from hair or wool has been proposed as an appropriate material for producing films or cell cultivation scaffolds. The current study was performed to characterize two different approaches involving substrate coating based on keratin from human hair. Our goal was to evaluate cell growth behavior in these systems in comparison with a standard polystyrene substrate. The coating was made in two different ways: (i) by trichloroacetic acid precipitation or (ii) by casting a keratin nanosuspension. The resulting films were characterized using SDS-PAGE, SEM, and X-ray studies. The growth behaviors of twelve cell lines on the keratin films and on polystyrene were estimated using proliferation studies. Furthermore, we assessed the cell detachment behavior during trypsinization and the seeding efficiency. For epithelial cell lines with tight junction proteins, the transepithelial electrical resistance was measured and compared with values achieved using common coating materials. Both of the keratin coatings exhibited similar protein patterns and X-ray diffraction profiles, but we also detected differences in the transparency and ultrastructural surface morphologies. Culture dishes coated with keratin nanoparticles were used to create a transparent substrate that supports cell adherence and improves cell growth as compared with uncoated polystyrene or coatings that use trichloroacetic acid precipitation. We conclude that this coating method may be a new promising substrate for standard cell cultivation.

PMID: 19783297 [PubMed - as supplied by publisher]


Interaction of human mesenchymal stem cells with osteopontin coated hydroxyapatite surfaces.
September 29, 2009 at 6:18 am

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Interaction of human mesenchymal stem cells with osteopontin coated hydroxyapatite surfaces.

Colloids Surf B Biointerfaces. 2009 Aug 25;

Authors: Jensen T, Dolatshahi-Pirouz A, Foss M, Baas J, Lovmand J, Duch M, Pedersen FS, Kassem M, Bünger C, Søballe K, Besenbacher F

In vitro studies of the initial attachment, spreading and motility of human bone mesenchymal stem cells have been carried out on bovine osteopontin (OPN) coated hydroxyapatite (HA) and gold (Au) model surfaces. The adsorption of OPN extracted from bovine milk was monitored by the quartz crystal microbalance with dissipation (QCM-D) and the ellipsometry techniques, and the OPN coated surfaces were further investigated by antigen-antibody interaction. It is shown that the OPN surface mass density is significantly lower and that the number of antibodies binding to the resulting OPN layers is significantly higher on the HA as compared to the Au surfaces. The initial attachment, spreading and motility of human mesenchymal stem cells show a larger cell area, a faster arrangement of vinculin in the basal cell membrane and more motile cells on the OPN coated HA surfaces as compared to the OPN coated Au surfaces and to the uncoated Au and HA surfaces. These in vitro results indicate that there may be great potential for OPN coated biomaterials, for instance as functional protein coatings or drug delivery systems on orthopaedic implants or scaffolds for tissue-engineering.

PMID: 19783129 [PubMed - as supplied by publisher]


Regenerative medicine: A primer for paediatricians.
September 29, 2009 at 6:18 am

Related Articles

Regenerative medicine: A primer for paediatricians.

Early Hum Dev. 2009 Sep 25;

Authors: Polak DJ

Regenerative medicine is a multidisciplinary field concerned with the replacement, repair or restoration of injured tissues. Cell therapy and tissue engineering are part of the broader remit of regenerative medicine. The ultimate aim is to provide safe and efficient therapies for a large number of clinical conditions. Novel regenerative therapies are already in use in initial clinical trials. The main components of regenerative medicine are cells and specially designed materials. A vast variety of cells types are currently used including: adult and stem cells. Equally a large number of natural and man-made materials have been investigated. Despite of considerable advances many challenges lie ahead. These are summarised in this review article. The field is slowly maturing and the initial unhelpful hype has been replaced by a more measured, mature and realistic outlook.

PMID: 19783108 [PubMed - as supplied by publisher]


Thermosensitive injectable hyaluronic acid hydrogel for adipose tissue engineering.
September 29, 2009 at 6:18 am

Related Articles

Thermosensitive injectable hyaluronic acid hydrogel for adipose tissue engineering.

Biomaterials. 2009 Sep 25;

Authors: Tan H, Ramirez CM, Miljkovic N, Li H, Rubin JP, Marra KG

A series of thermosensitive copolymer hydrogels, aminated hyaluronic acid-g-poly(N-isopropylacrylamide) (AHA-g-PNIPAAm), were synthesized by coupling carboxylic end-capped PNIPAAm (PNIPAAm-COOH) to AHA through amide bond linkages. AHA was prepared by grafting adipic dihydrazide to the HA backbone and PNIPAAm-COOH copolymer was synthesized via a facile thermo-radical polymerization technique by polymerization of NIPAAm using 4,4'-azobis(4-cyanovaleric acid) as an initiator, respectively. The structure of AHA and AHA-g-PNIPAAm copolymer was determined by (1)H NMR. Two AHA-g-PNIPAAm copolymers with different weight ratios of PNIPAAm on the applicability of injectable hydrogels were characterized. The lower critical solution temperature (LCST) of AHA-g-PNIPAAm copolymers in PBS were measured as approximately 30 degrees C by rheological analysis, regardless of the grafting degrees. Enzymatic resistance of AHA-g-PNIPAAm hydrogels with 28% and 53% of PNIPAAm in 100U/mL hyaluronidase/PBS at 37 degrees C was 12.3% and 37.6% over 28 days, respectively. Equilibrium swelling ratios of AHA-g-PNIPAAm hydrogels with 28% of PNIPAAm were 21.5, and significantly decreased to 13.3 with 53% of PNIPAAm in PBS at 37 degrees C. Results from SEM observations confirm a porous 3D AHA-g-PNIPAAm hydrogel structure with interconnected pores after freeze-drying and the pore diameter depends on the weight ratios of PNIPAAm. Encapsulation of human adipose-derived stem cells (ASCs) within hydrogels showed the AHA-g-PNIPAAm copolymers were noncytotoxic and preserved the viability of the entrapped cells. A preliminary in vivo study demonstrated the usefulness of the AHA-g-PNIPAAm copolymer as an injectable hydrogel for adipose tissue engineering. This newly described thermoresponsive AHA-g-PNIPAAm copolymer demonstrated attractive properties to serve as cell or pharmaceutical delivery vehicles for a variety of tissue engineering applications.

PMID: 19783043 [PubMed - as supplied by publisher]


The nanofibrous architecture of poly(l-lactic acid)-based functional copolymers.
September 29, 2009 at 6:18 am

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The nanofibrous architecture of poly(l-lactic acid)-based functional copolymers.

Biomaterials. 2009 Sep 25;

Authors: Liu X, Ma PX

It remains a challenge to synthesize functional materials that can develop advanced scaffolding architectures for tissue engineering. In this study, a series of biodegradable amphiphilic poly(hydroxyalkyl (meth)acrylate)-graft-poly(l-lactic acid) (PHAA-g-PLLA) copolymers have been synthesized and fabricated into nano-fibrous scaffolds. These copolymers can be further functionalized, are more hydrophilic, and have faster degradation rates than the PLLA homopolymer, which are advantageous for certain tissue engineering applications. First, PLLA-based macromonomers were prepared by using functional hydroxyalkyl (meth)acrylates (HAA) as initiators. The PHAA-g-PLLA copolymers were then synthesized using free radical copolymerization of PLLA-based macromonomers and HAA. Nano-fibrous architecture was created using a thermally induced phase separation technique from these functional PHAA-g-PLLA copolymers. The nano-fibrous structure mimics the architecture of natural collagen matrix at the nanometer scale. The effects of the macromonomer composition, copolymer composition, blending ratio, and solvent selection on nano-scale structures were studied. In general, the nano-fibrous structure was created when the amount of HAA in the macromonomer was low. By increasing the amount of HAA in the macromonomer, microspheres with nano-fibrous surfaces were obtained. Further increasing the amount of HAA led to the creation of microspheres with leaf-like surfaces. These PLLA-based materials had much faster degradation rates than the PLLA, and could be completely degraded from several weeks to a few months depending on their composition and molecular weight. Furthermore, the PHAA-g-PLLA copolymers possess functional hydroxyl groups, which can be used to couple with bioactive molecules to control cell-material interactions. Therefore, these biodegradable functional copolymers have the design flexibility to fabricate various biomimetic materials for tissue engineering applications.

PMID: 19783035 [PubMed - as supplied by publisher]


Modulating cellular adhesion through nanotopography.
September 29, 2009 at 6:18 am

Related Articles

Modulating cellular adhesion through nanotopography.

Biomaterials. 2009 Sep 25;

Authors: Decuzzi P, Ferrari M

Cellular adhesion is a fundamental process in the development of scaffolds for tissue engineering; in the design of biosensors and in preparing antibacterial substrates. A theoretical model is presented for predicting the strength of cellular adhesion to originally inert surfaces as a function of the substrate topography, accounting for both specific (ligand-receptor) and non-specific interfacial interactions. Three regimes have been identified depending on the surface energy (gamma) of the substrate: for small gamma, any increase in roughness is detrimental to adhesion; for large gamma, an optimal roughness exists that maximizes adhesion; and for intermediate gamma, surface roughness has a minor effect on adhesion. The results presented are in qualitative agreement with several experimental observations and can capture the long-term equilibrium configuration of the system. The model proposed supports the notion for rationally designing substrates where topography and physico-chemical properties are tailored to favour cellular proliferation whilst repelling bacterial adhesion.

PMID: 19783034 [PubMed - as supplied by publisher]

 

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