Saturday, May 21, 2011

5/22 TE-RegenMed-StemCell feed

     
    TE-RegenMed-StemCell feed    
   
An animal model to study regenerative endodontics.
May 21, 2011 at 11:44 AM
 

An animal model to study regenerative endodontics.

J Endod. 2011 Feb;37(2):197-202

Authors: Torabinejad M, Corr R, Buhrley M, Wright K, Shabahang S

A growing body of evidence is demonstrating the possibility for regeneration of tissues within the pulp space and continued root development in teeth with necrotic pulps and open apices. There are areas of research related to regenerative endodontics that need to be investigated in an animal model. The purpose of this study was to investigate ferret cuspid teeth as a model to investigate factors involved in regenerative endodontics.

PMID: 21238802 [PubMed - indexed for MEDLINE]

   
   
A Nanocage for Nanomedicine: Polyhedral Oligomeric Silsesquioxane (POSS).
May 21, 2011 at 11:44 AM
 

A Nanocage for Nanomedicine: Polyhedral Oligomeric Silsesquioxane (POSS).

Macromol Rapid Commun. 2011 May 19;

Authors: Ghanbari H, Cousins BG, Seifalian AM

Ground-breaking advances in nanomedicine (defined as the application of nanotechnology in medicine) have proposed novel therapeutics and diagnostics, which can potentially revolutionize current medical practice. Polyhedral oligomeric silsesquioxane (POSS) with a distinctive nanocage structure consisting of an inner inorganic framework of silicon and oxygen atoms, and an outer shell of organic functional groups is one of the most promising nanomaterials for medical applications. Enhanced biocompatibility and physicochemical (material bulk and surface) properties have resulted in the development of a wide range of nanocomposite POSS copolymers for biomedical applications, such as the development of biomedical devices, tissue engineering scaffolds, drug delivery systems, dental applications, and biological sensors. The application of POSS nanocomposites in combination with other nanostructures has also been investigated including silver nanoparticles and quantum dot nanocrystals. Chemical functionalization confers antimicrobial efficacy to POSS, and the use of polymer nanocomposites provides a biocompatible surface coating for quantum dot nanocrystals to enhance the efficacy of the materials for different biomedical and biotechnological applications. Interestingly, a family of POSS-containing nanocomposite materials can be engineered either as completely non-biodegradable materials or as biodegradable materials with tuneable degradation rates required for tissue engineering applications. These highly versatile POSS derivatives have created new horizons for the field of biomaterials research and beyond. Currently, the application of POSS-containing polymers in various fields of nanomedicine is under intensive investigation with expectedly encouraging outcomes.

PMID: 21598339 [PubMed - as supplied by publisher]

   
   
Cardiac Effects of Muscarinic Receptor Antagonists Used for Voiding Dysfunction.
May 21, 2011 at 11:44 AM
 

Cardiac Effects of Muscarinic Receptor Antagonists Used for Voiding Dysfunction.

Br J Clin Pharmacol. 2010 Sep 29;

Authors: Andersson KE, Campeau L, Olshansky B

Antimuscarinic agents are the main drugs used to treat patients with the overactive bladder (OAB) syndrome, defined as urgency, with or without urgency incontinence, usually with increased daytime frequency and nocturia. Since the treatment is not curative and since OAB is a chronic disease, treatment may be life-long. Antimuscarinics are generally considered to be "safe" drugs, but among the more serious concerns related to their use is the risk of cardiac adverse effects, particularly increases in heart rate (HR) and QT-prolongation and induction of polymorphic ventricular tachycardia (torsade de pointes). An elevated resting HR have been linked to overall increased morbidity and mortality, and particularly in patients with cardiovascular diseases. QT prolongation and its consequences are not related to blockade of muscarinic receptors, but rather linked to inhibition of the hERG potassium channel in the heart. However, experience with terodiline, an antimuscarinic drug causing torsade de pointes in patients, have placed the whole drug class under scrutiny. The potential of the different antimuscarinic agents to increase HR and/or prolong the QT time has not been extensively explored for all agents in clinical use. Differences between drugs cannot be excluded, but risk assessments based on available evidence are not possible.

PMID: 21595741 [PubMed - as supplied by publisher]

   
   
Revitalization of tooth with necrotic pulp and open apex by using platelet-rich plasma: a case report.
May 21, 2011 at 11:44 AM
 

Revitalization of tooth with necrotic pulp and open apex by using platelet-rich plasma: a case report.

J Endod. 2011 Feb;37(2):265-8

Authors: Torabinejad M, Turman M

A growing body of evidence is demonstrating the possibility for regeneration of tissues within the pulp space and continued root development in teeth with necrotic pulps and open apexes. The purpose of this case report is to add a regenerative endodontic case to the existing literature about using platelet-rich plasma (PRP).

PMID: 21238815 [PubMed - indexed for MEDLINE]

   
   
Evaluation of the delivery of mesenchymal stem cells into the root canal space of necrotic immature teeth after clinical regenerative endodontic procedure.
May 21, 2011 at 11:44 AM
 

Evaluation of the delivery of mesenchymal stem cells into the root canal space of necrotic immature teeth after clinical regenerative endodontic procedure.

J Endod. 2011 Feb;37(2):133-8

Authors: Lovelace TW, Henry MA, Hargreaves KM, Diogenes A

Immature teeth with open apices treated with conventional nonsurgical root canal treatment often have a poor prognosis as a result of the increased risk of fracture and susceptibility to recontamination. Regenerative endodontics represents a new treatment modality that focuses on reestablishment of pulp vitality and continued root development. This clinical procedure relies on the intracanal delivery of a blood clot (scaffold), growth factors (possibly from platelets and dentin), and stem cells. However, to date, the clinical presence of stem cells in the canal space after this procedure has not been demonstrated. The purpose of this clinical study was to evaluate whether regenerative endodontic procedures are able to deliver stem cells into the canal space of immature teeth in young patients and to identify the possible tissue origin for these cells.

PMID: 21238791 [PubMed - indexed for MEDLINE]

   
   
Chromatin "prepattern" and histone modifiers in a fate choice for liver and pancreas.
May 21, 2011 at 11:44 AM
 

Chromatin "prepattern" and histone modifiers in a fate choice for liver and pancreas.

Science. 2011 May 20;332(6032):963-6

Authors: Xu CR, Cole PA, Meyers DJ, Kormish J, Dent S, Zaret KS

Transcriptionally silent genes can be marked by histone modifications and regulatory proteins that indicate the genes' potential to be activated. Such marks have been identified in pluripotent cells, but it is unknown how such marks occur in descendant, multipotent embryonic cells that have restricted cell fate choices. We isolated mouse embryonic endoderm cells and assessed histone modifications at regulatory elements of silent genes that are activated upon liver or pancreas fate choices. We found that the liver and pancreas elements have distinct chromatin patterns. Furthermore, the histone acetyltransferase P300, recruited via bone morphogenetic protein signaling, and the histone methyltransferase Ezh2 have modulatory roles in the fate choice. These studies reveal a functional "prepattern" of chromatin states within multipotent progenitors and potential targets to modulate cell fate induction.

PMID: 21596989 [PubMed - in process]

   
   
Skin Bioengineering: Preclinical and Clinical Applications.
May 21, 2011 at 11:44 AM
 

Skin Bioengineering: Preclinical and Clinical Applications.

Actas Dermosifiliogr. 2011 May 17;

Authors: Martínez-Santamaría L, Guerrero-Aspizua S, Del Río M

Regenerative Medicine is an emerging field that combines basic research and clinical observations in order to identify the elements required to replace damaged tissues and organs in vivo and to stimulate the body's intrinsic regenerative capacity. Great benefits are expected in this field as researchers take advantage of the potential regenerative properties of both embryonic and adult stem cells, and more recently, of induced pluripotent stem cells. Bioengineered skin emerged mainly in response to a critical need for early permanent coverage of extensive burns. Later this technology was also applied to the treatment of chronic ulcers. Our group has established a humanized mouse model of skin grafting that involves the use of bioengineered human skin in immunodeficient mice. This model is suitable for the study of physiologic and pathologic cutaneous processes and the evaluation of treatment strategies for skin diseases, including protocols for gene and cell therapy and tissue engineering.

PMID: 21596361 [PubMed - as supplied by publisher]

   
   
Nanofiber-mediated controlled release of siRNA complexes for long term gene-silencing applications.
May 21, 2011 at 11:44 AM
 

Nanofiber-mediated controlled release of siRNA complexes for long term gene-silencing applications.

Biomaterials. 2011 May 17;

Authors: Rujitanaroj PO, Wang YC, Wang J, Chew SY

Nanofiber scaffold-mediated delivery of small-interfering RNA (siRNA) holds great potential in regenerative medicine by providing biomimicking topographical signals and enhanced gene silencing effects to seeded cells. While the delivery of naked siRNA was demonstrated previously using poly (ε-caprolactone) (PCL) nanofibers, the resulting siRNA release kinetics and gene knockdown efficiencies were sub-optimal. In this study, we investigated the feasibility of encapsulating siRNA and transfection reagent (TKO) complexes within nanofibers comprising of a copolymer of caprolactone and ethyl ethylene phosphate (PCLEEP, diameter ∼ 400 nm). Sustained release of bioactive naked siRNA and siRNA/TKO complexes were obtained for at least 28 days. By copolymerizing EEP with caprolactone, siRNA release was significantly enhanced (total siRNA that was released by day 49 was ∼ 89.3-97.2% as compared to previously reported 3% by plain PCL nanofiber delivery). Using GAPDH as the model protein, bioactivity analyses by supernatant transfection revealed the partial retention of bioactivity of naked siRNA and siRNA/TKO complexes for at least 30 days. In particular, GAPDH siRNA/TKO supernatant alone induced significant gene silencing (∼40%), indicating the feasibility of co-encapsulating siRNA and transfection reagent within a single scaffold construct for sustained delivery. Direct culture of cells on siRNA incorporated scaffolds for scaffold-mediated gene transfection revealed significant gene knockdown even in the absence of transfection reagent (21.3% knockdown efficiency by scaffolds incorporating naked siRNA only). By encapsulating siRNA/TKO complexes, more significant gene knockdown was obtained (30.9% knockdown efficiency as compared to previously reported 18% by plain PCL scaffold-mediated transfection). Taken together, the results demonstrated the feasibility of co-encapsulating siRNA-transfection reagent complexes within a single nanofiber construct for sustained siRNA delivery and enhanced gene knockdown efficiency. The study also highlights the potential of PCLEEP as a platform for tailoring siRNA release kinetics for long-term gene silencing applications.

PMID: 21596430 [PubMed - as supplied by publisher]

   
   
[The medical biochemistry studies for 50 years (from biochemistry to molecular medicine and regenerative medicine)].
May 21, 2011 at 11:44 AM
 

[The medical biochemistry studies for 50 years (from biochemistry to molecular medicine and regenerative medicine)].

Sheng Li Ke Xue Jin Zhan. 2011 Feb;42(1):1-5

Authors: Yang TS

PMID: 21595179 [PubMed - in process]

   
   
Growth of Engineered Human Myocardium With Mechanical Loading and Vascular Coculture.
May 21, 2011 at 11:44 AM
 

Growth of Engineered Human Myocardium With Mechanical Loading and Vascular Coculture.

Circ Res. 2011 May 19;

Authors: Tulloch NL, Muskheli V, Razumova MV, Korte FS, Regnier M, Hauch KD, Pabon L, Reinecke H, Murry CE

Rationale: The developing heart requires both mechanical load and vascularization to reach its proper size, yet the regulation of human heart growth by these processes is poorly understood. Objective: We seek to elucidate the responses of immature human myocardium to mechanical load and vascularization using tissue engineering approaches. Methods and Results: Using human embryonic stem cell and human-induced pluripotent stem cell-derived cardiomyocytes in a 3-dimensional collagen matrix, we show that uniaxial mechanical stress conditioning promotes 2-fold increases in cardiomyocyte and matrix fiber alignment and enhances myofibrillogenesis and sarcomeric banding. Furthermore, cyclic strain markedly increases cardiomyocyte hypertrophy (2.2-fold) and proliferation rates (21%) versus unstrained constructs. Addition of endothelial cells enhances cardiomyocyte proliferation under all stress conditions (14% to 19%), and addition of stromal supporting cells enhances formation of vessellike structures by ≈10-fold. Furthermore, these optimized human cardiac tissue constructs generate Starling curves, increasing their active force in response to increased resting length. When transplanted onto hearts of athymic rats, the human myocardium survives and forms grafts closely apposed to host myocardium. The grafts contain human microvessels that are perfused by the host coronary circulation. Conclusions: Our results indicate that both mechanical load and vascular cell coculture control cardiomyocyte proliferation, and that mechanical load further controls the hypertrophy and architecture of engineered human myocardium. Such constructs may be useful for studying human cardiac development as well as for regenerative therapy.

PMID: 21597009 [PubMed - as supplied by publisher]

   
   
Stem cell sources for regenerative medicine: the immunological point of view.
May 21, 2011 at 11:44 AM
 

Stem cell sources for regenerative medicine: the immunological point of view.

Semin Immunopathol. 2011 May 21;

Authors: Preynat-Seauve O, Krause KH

Stem cell transplantation consists in the introduction of stem cells or derived products in a diseased organism. Because of the differentiation properties of stem cells, the goal is to replace damaged cells or tissues. Numbers of stem cell were identified and isolated from embryos, fetuses, or adult organs, harboring different properties, and thus providing multiple strategies of regenerative medicine for different diseases. More recently, the artificial induction of stemness properties in adult somatic cells has proposed a new way to generate stem cells. One important concern of stem cell therapy is the possible risk that transplanted stem cells could be rejected by the recipient's immune system. Depending on their source, stem cell transplantation is associated with diverse immunological situations. If some sources allow autologous transplantation, others cannot bypass an allogeneic context between the donor and the recipient. This review summarizes all of the stem cell sources for regenerative medicine and the immunological questions associated to their use. Regarding the emerging strategies compatible with autologous transplantation, this article points notably the complexity of the choice between the immunological safety and the specific advantages of allogeneic stem cells.

PMID: 21598094 [PubMed - as supplied by publisher]

   
   
The effects of low-level laser irradiation on differentiation and proliferation of human bone marrow mesenchymal stem cells into neurons and osteoblasts-an in vitro study.
May 21, 2011 at 11:44 AM
 

The effects of low-level laser irradiation on differentiation and proliferation of human bone marrow mesenchymal stem cells into neurons and osteoblasts-an in vitro study.

Lasers Med Sci. 2011 May 20;

Authors: Soleimani M, Abbasnia E, Fathi M, Sahraei H, Fathi Y, Kaka G

Bone marrow-derived mesenchymal stem cells (BMSCs) are promising for use in regenerative medicine. Several studies have shown that low-level laser irradiation (LLLI) could affect the differentiation and proliferation of MSCs. The aim of this study was to examine the influence of LLLI at different energy densities on BMSCs differentiation into neuron and osteoblast. Human BMSCs were cultured and induced to differentiate to either neuron or osteoblast in the absence or presence of LLLI. Gallium aluminum arsenide (GaAlAs) laser irradiation (810 nm) was applied at days 1, 3, and 5 of differentiation process at energy densities of 3 or 6 J/cm(2) for BMSCs being induced to neurons, and 2 or 4 J/cm(2) for BMSCs being induced to osteoblasts. BMSCs proliferation was evaluated by MTT assay on the seventh day of differentiation. BMSCs differentiation to neurons was assessed by immunocytochemical analysis of neuron-specific enolase on the seventh day of differentiation. BMSCs differentiation to osteoblast was tested on the second, fifth, seventh, and tenth day of differentiation via analysis of alkaline phosphatase (ALP) activity. LLLI promoted BMSCs proliferation significantly at all energy densities except for 6 J/cm(2) in comparison to control groups on the seventh day of differentiation. LLLI at energy densities of 3 and 6 J/cm(2) dramatically facilitated the differentiation of BMSCs into neurons (p < 0.001). Also, ALP activity was significantly enhanced in irradiated BMSCs differentiated to osteoblast on the second, fifth, seventh, and tenth day of differentiation (p < 0.001 except for the second day). Using LLLI at 810 nm wavelength enhances BMSCs differentiation into neuron and osteoblast in the range of 2-6 J/cm(2), and at the same time increases BMSCs proliferation (except for 6 J/cm(2)). The effect of LLLI on differentiation and proliferation of BMSCs is dose-dependent. Considering these findings, LLLI could improve current in vitro methods of differentiating BMSCs prior to transplantation.

PMID: 21597948 [PubMed - as supplied by publisher]

   
   
Amnion-derived stem cells: in quest of clinical applications.
May 21, 2011 at 11:44 AM
 

Amnion-derived stem cells: in quest of clinical applications.

Stem Cell Res Ther. 2011 May 19;2(3):25

Authors: Miki T

ABSTRACT: In the promising field of regenerative medicine, human perinatal stem cells are of great interest as potential stem cells with clinical applications. Perinatal stem cells could be isolated from normally discarded human placentae, which are an ideal cell source in terms of availability, the fewer number of ethical concerns, less DNA damage, and so on. Numerous studies have demonstrated that some of the placenta-derived cells possess stem cell characteristics like pluripotent differentiation ability, particularly in amniotic epithelial (AE) cells. Term human amniotic epithelium contains a relatively large number of stem cell marker-positive cells as an adult stem cell source. In this review, we introduce a model theory of why so many AE cells possess stem cell characteristics. We also describe previous work concerning the therapeutic applications and discuss the pluripotency of the AE cells and potential pitfalls for amnion-derived stem cell research.

PMID: 21596003 [PubMed - as supplied by publisher]

   
   
Stem cell therapy for heart diseases.
May 21, 2011 at 8:56 AM
 

Stem cell therapy for heart diseases.

Br Med Bull. 2011 May 19;

Authors: Mozid AM, Arnous S, Sammut EC, Mathur A

Background Cardiovascular disease is the leading cause of morbidity and mortality worldwide. Despite the advances in medical and catheter-based therapy for acute myocardial infarction the 1-year mortality remains as high as 13% and the 5-year prognosis for patients with heart failure remains as high as 50%. Left ventricular systolic dysfunction, a major determinant of prognosis, is associated with significant loss of cardiomyocytes which was previously thought to be irreversible as the heart was considered a post-mitotic organ. Sources of data Review of literature published in peer reviewed journals and ClinicalTrials.Gov website. Areas of agreement There is now growing evidence that the human heart is capable of undergoing repair and in recent years there has been an increase in basic and clinical research with the aim of harnessing the regenerative properties of stem cells in order to facilitate restoration of myocardial function. Areas of controversy The mechanisms of action of cell therapy with regards to cardiac repair remain unsatisfactorily understood and the magnitude of benefit demonstrated in animal models is yet to be fully translated in humans. Growing points The number of clinical trials continues to increase and include treating patients with acute myocardial infarction and chronic heart failure secondary to ischaemic heart disease or dilated cardiomyopathy. Areas timely for developing research The future of this field of research will require closer collaboration between scientists and clinicians to understand how cell therapy works and to define the ideal cell type and method of delivery to be able to derive maximum benefit.

PMID: 21596713 [PubMed - as supplied by publisher]

   
   
Stem cell sources for regenerative medicine: the immunological point of view.
May 21, 2011 at 8:56 AM
 

Stem cell sources for regenerative medicine: the immunological point of view.

Semin Immunopathol. 2011 May 21;

Authors: Preynat-Seauve O, Krause KH

Stem cell transplantation consists in the introduction of stem cells or derived products in a diseased organism. Because of the differentiation properties of stem cells, the goal is to replace damaged cells or tissues. Numbers of stem cell were identified and isolated from embryos, fetuses, or adult organs, harboring different properties, and thus providing multiple strategies of regenerative medicine for different diseases. More recently, the artificial induction of stemness properties in adult somatic cells has proposed a new way to generate stem cells. One important concern of stem cell therapy is the possible risk that transplanted stem cells could be rejected by the recipient's immune system. Depending on their source, stem cell transplantation is associated with diverse immunological situations. If some sources allow autologous transplantation, others cannot bypass an allogeneic context between the donor and the recipient. This review summarizes all of the stem cell sources for regenerative medicine and the immunological questions associated to their use. Regarding the emerging strategies compatible with autologous transplantation, this article points notably the complexity of the choice between the immunological safety and the specific advantages of allogeneic stem cells.

PMID: 21598094 [PubMed - as supplied by publisher]

   
   
Alveolar osseous defect in rat for cell therapy: preliminary report.
May 21, 2011 at 6:17 AM
 

Alveolar osseous defect in rat for cell therapy: preliminary report.

Acta Cir Bras. 2010 Aug;25(4):313-7

Authors: Raposo-Amaral CE, Kobayashi GS, Almeida AB, Bueno DF, Freitas FR, Vulcano LC, Passos-Bueno MR, Alonso N

To study were to reproduce an alveolar bone defect model in Wistar rats to be used for testing the efficacy of stem cell therapies. Additionally, we also aimed to determine the osteogenesis process of this osseous defect in the 1 month period post-surgery.

PMID: 20676486 [PubMed - indexed for MEDLINE]

   
   
A Nanocage for Nanomedicine: Polyhedral Oligomeric Silsesquioxane (POSS).
May 21, 2011 at 6:17 AM
 

A Nanocage for Nanomedicine: Polyhedral Oligomeric Silsesquioxane (POSS).

Macromol Rapid Commun. 2011 May 19;

Authors: Ghanbari H, Cousins BG, Seifalian AM

Ground-breaking advances in nanomedicine (defined as the application of nanotechnology in medicine) have proposed novel therapeutics and diagnostics, which can potentially revolutionize current medical practice. Polyhedral oligomeric silsesquioxane (POSS) with a distinctive nanocage structure consisting of an inner inorganic framework of silicon and oxygen atoms, and an outer shell of organic functional groups is one of the most promising nanomaterials for medical applications. Enhanced biocompatibility and physicochemical (material bulk and surface) properties have resulted in the development of a wide range of nanocomposite POSS copolymers for biomedical applications, such as the development of biomedical devices, tissue engineering scaffolds, drug delivery systems, dental applications, and biological sensors. The application of POSS nanocomposites in combination with other nanostructures has also been investigated including silver nanoparticles and quantum dot nanocrystals. Chemical functionalization confers antimicrobial efficacy to POSS, and the use of polymer nanocomposites provides a biocompatible surface coating for quantum dot nanocrystals to enhance the efficacy of the materials for different biomedical and biotechnological applications. Interestingly, a family of POSS-containing nanocomposite materials can be engineered either as completely non-biodegradable materials or as biodegradable materials with tuneable degradation rates required for tissue engineering applications. These highly versatile POSS derivatives have created new horizons for the field of biomaterials research and beyond. Currently, the application of POSS-containing polymers in various fields of nanomedicine is under intensive investigation with expectedly encouraging outcomes.

PMID: 21598339 [PubMed - as supplied by publisher]

   
   
Local tolerance and efficiency of two prototype collagen matrices to increase the width of keratinized tissue.
May 21, 2011 at 6:17 AM
 

Local tolerance and efficiency of two prototype collagen matrices to increase the width of keratinized tissue.

J Clin Periodontol. 2011 Feb;38(2):173-9

Authors: Jung RE, Hürzeler MB, Thoma DS, Khraisat A, Hämmerle CH

to evaluate the local tolerance and efficiency of two experimental collagen matrices to increase the width of keratinized tissue.

PMID: 21092054 [PubMed - indexed for MEDLINE]

   
   
Genetic modification of donor hepatocytes improves therapeutic efficacy for hemophilia B in mice.
May 21, 2011 at 6:17 AM
 

Genetic modification of donor hepatocytes improves therapeutic efficacy for hemophilia B in mice.

Cell Transplant. 2010;19(9):1169-80

Authors: Wu YM, Kao CY, Huang YJ, Yu IS, Lee HS, Lai HS, Lee PH, Lin CN, Lin SW

Hepatocyte transplantation (Tx) holds promise for curing genetic liver diseases. However, a limited number of donor hepatocytes can be transplanted into the host liver. Recipient preconditioning and donor cell engineering are under investigation to improve cell engraftment. In theory, genetically engineered cells secreting therapeutic proteins with superior function could compensate for poor engraftment efficiency. We have generated a bioengineered human coagulation factor IX (FIX) with augmented specific activity (named FIX-Triple). The aim of this study was to evaluate therapeutic efficacy of cell therapy using hemophilia B (HB) as a disease model by transplanting FIX-Triple-secreting hepatocytes. The donor hepatocytes were isolated from FIX-Triple knock-in (KI) or FIX-WT (wild-type) KI mice and transplanted intrasplenically into FIX knock-out (KO) mice. FIX-Triple KI recipients exhibited fourfold higher plasma FIX clotting activity than FIX-WT KI recipients. By repeated Txs, the clotting activity of FIX-Triple KI recipients even increased to more than 10% of normal mouse plasma. The engraftment and FIX production efficiencies of transplanted cells were equivalent between the FIX-WT KI and FIX-Triple KI donors. A hemostatic function assay showed that FIX-Triple KI recipients with repeated Txs had more enhanced clot kinetics and a greater maximum rate of thrombus generation than those with a single Tx. Moreover, FIX inhibitors in these recipients rarely developed. In conclusion, hepatocyte Tx with genetically engineered donor cells is an effective therapeutic strategy for HB.

PMID: 20412633 [PubMed - indexed for MEDLINE]

   
   
Growth of Engineered Human Myocardium With Mechanical Loading and Vascular Coculture.
May 21, 2011 at 6:17 AM
 

Growth of Engineered Human Myocardium With Mechanical Loading and Vascular Coculture.

Circ Res. 2011 May 19;

Authors: Tulloch NL, Muskheli V, Razumova MV, Korte FS, Regnier M, Hauch KD, Pabon L, Reinecke H, Murry CE

Rationale: The developing heart requires both mechanical load and vascularization to reach its proper size, yet the regulation of human heart growth by these processes is poorly understood. Objective: We seek to elucidate the responses of immature human myocardium to mechanical load and vascularization using tissue engineering approaches. Methods and Results: Using human embryonic stem cell and human-induced pluripotent stem cell-derived cardiomyocytes in a 3-dimensional collagen matrix, we show that uniaxial mechanical stress conditioning promotes 2-fold increases in cardiomyocyte and matrix fiber alignment and enhances myofibrillogenesis and sarcomeric banding. Furthermore, cyclic strain markedly increases cardiomyocyte hypertrophy (2.2-fold) and proliferation rates (21%) versus unstrained constructs. Addition of endothelial cells enhances cardiomyocyte proliferation under all stress conditions (14% to 19%), and addition of stromal supporting cells enhances formation of vessellike structures by ≈10-fold. Furthermore, these optimized human cardiac tissue constructs generate Starling curves, increasing their active force in response to increased resting length. When transplanted onto hearts of athymic rats, the human myocardium survives and forms grafts closely apposed to host myocardium. The grafts contain human microvessels that are perfused by the host coronary circulation. Conclusions: Our results indicate that both mechanical load and vascular cell coculture control cardiomyocyte proliferation, and that mechanical load further controls the hypertrophy and architecture of engineered human myocardium. Such constructs may be useful for studying human cardiac development as well as for regenerative therapy.

PMID: 21597009 [PubMed - as supplied by publisher]

   
   
Nanomaterials and Hydrogel Scaffolds for Articular Cartilage Regeneration.
May 21, 2011 at 6:17 AM
 

Nanomaterials and Hydrogel Scaffolds for Articular Cartilage Regeneration.

Tissue Eng Part B Rev. 2011 May 20;

Authors: Reddi AH, Becerra J, Andrades JA

Osteoarthritis (OA) is a major clinical and scientific challenge. The degradation of articular cartilage in the joints is a common manifestation of painful arthritis. The regeneration of articular cartilage in OA is an unmet clinical need. The assembly of articular cartilage by tissue engineering towards complete regeneration is the goal of most scientists and surgeons. The key ingredients for regeneration are signals, stem cells, and scaffolds. This brief review focuses on the scaffold, with special emphasis on hydrogels and nanomaterials for the assembly of tissue engineered cartilage, and ultimately leading to the total regeneration of articular cartilage in the joints.

PMID: 21595612 [PubMed - as supplied by publisher]

   
   
Skin Bioengineering: Preclinical and Clinical Applications.
May 21, 2011 at 6:17 AM
 

Skin Bioengineering: Preclinical and Clinical Applications.

Actas Dermosifiliogr. 2011 May 17;

Authors: Martínez-Santamaría L, Guerrero-Aspizua S, Del Río M

Regenerative Medicine is an emerging field that combines basic research and clinical observations in order to identify the elements required to replace damaged tissues and organs in vivo and to stimulate the body's intrinsic regenerative capacity. Great benefits are expected in this field as researchers take advantage of the potential regenerative properties of both embryonic and adult stem cells, and more recently, of induced pluripotent stem cells. Bioengineered skin emerged mainly in response to a critical need for early permanent coverage of extensive burns. Later this technology was also applied to the treatment of chronic ulcers. Our group has established a humanized mouse model of skin grafting that involves the use of bioengineered human skin in immunodeficient mice. This model is suitable for the study of physiologic and pathologic cutaneous processes and the evaluation of treatment strategies for skin diseases, including protocols for gene and cell therapy and tissue engineering.

PMID: 21596361 [PubMed - as supplied by publisher]

   
   
The Nature and Role of Periosteum in Bone and Cartilage Regeneration.
May 21, 2011 at 6:17 AM
 

The Nature and Role of Periosteum in Bone and Cartilage Regeneration.

Cells Tissues Organs. 2011 May 20;

Authors: Matsushima S, Isogai N, Jacquet R, Lowder E, Tokui T, Landis WJ

This study was undertaken to determine whether periosteum from different bone sources in a donor results in the same formation of bone and cartilage. In this case, periosteum obtained from the cranium and mandible (examples of tissue supporting intramembranous ossification) and the radius and ilium (examples of tissues supporting endochondral ossification) of individual calves was used to produce tissue-engineered constructs that were implanted in nude mice and then retrieved after 10 and 20 weeks. Specimens were compared in terms of their osteogenic and chondrogenic potential by radiography, histology, and gene expression levels. By 10 weeks of implantation and more so by 20 weeks, constructs with cranial periosteum had developed to the greatest extent, followed in order by ilium, radius, and mandible periosteum. All constructs, particularly with cranial tissue although minimally with mandibular periosteum, had mineralized by 10 weeks on radiography and stained for proteoglycans with safranin-O red (cranial tissue most intensely and mandibular tissue least intensely). Gene expression of type I collagen, type II collagen, runx2, and bone sialoprotein (BSP) was detectable on QRT-PCR for all specimens at 10 and 20 weeks. By 20 weeks, the relative gene levels were: type I collagen, ilium >> radial ≥ cranial ≥ mandibular; type II collagen, radial > ilium > cranial ≥ mandibular; runx2, cranial >>> radial > mandibular ≥ ilium; and BSP, ilium ≥ radial > cranial > mandibular. These data demonstrate that the osteogenic and chondrogenic capacity of the various constructs is not identical and depends on the periosteal source regardless of intramembranous or endochondral ossification. Based on these results, cranial and mandibular periosteal tissues appear to enhance bone formation most and least prominently, respectively. The appropriate periosteal choice for bone and cartilage tissue engineering and regeneration should be a function of its immediate application as well as other factors besides growth rate.

PMID: 21597269 [PubMed - as supplied by publisher]

   
   
Efficient genetic modification of cynomolgus monkey embryonic stem cells with lentiviral vectors.
May 21, 2011 at 6:17 AM
 

Efficient genetic modification of cynomolgus monkey embryonic stem cells with lentiviral vectors.

Cell Transplant. 2010;19(9):1181-93

Authors: Li W, Liu C, Qin J, Zhang L, Chen R, Chen J, Yu X, Wu G, Lahn BT, Fu Y, Xiang AP

Embryonic stem (ES) cells have the ability to undergo indefinite self-renewal in vitro and give rise during development to derivatives of all three primary germ layers (ectoderm, endoderm, and mesoderm), which make them a highly prized reagent in cell and gene therapy. Efficient introduction of various genes of interest into primate ES cells has proven to be difficult. Here, we demonstrated that the self-inactivating HIV-1-based lentiviral vectors constructed by MultiSite gateway technology are efficient tools for the transduction of cynomolgus monkey (Macaca fasicularis) ES (cmES) cells. After antibiotic selection, all of the transduced cells can stably express the reporter gene (humanized Renilla GFP or dTomato) while maintaining their stem cell properties, including continuous expression of stem cell markers, alkaline phosphatase (AKP), OCT-4, SSEA-4, and TRA-1-60, formation of embryoid bodies in vitro and teratomas in vivo containing derivatives of three embryonic germ layers. This approach will provide a useful tool for both gene function studies and in vivo cell tracking of stem cells.

PMID: 20447344 [PubMed - indexed for MEDLINE]

   
   
Dendronized polyaniline nanotubes for cardiac tissue engineering.
May 21, 2011 at 6:17 AM
 

Dendronized polyaniline nanotubes for cardiac tissue engineering.

Artif Organs. 2011 May;35(5):471-7

Authors: Moura RM, de Queiroz AA

Today, nanobiomaterials represent a very important class of biomaterials because they differ dramatically in their bulk precursors. The properties of these materials are determined by the size and morphology, thus creating a fascinating line in their physicochemical properties. Polyaniline nanotubes (PANINTs) are one of the most promising nanobiomaterials for cardiac tissue engineering applications due to their electroactive properties. The biocompatibility and low hydrophilic properties of PANINTs can be improved by their functionalization with the highly hydrophilic polyglycerol dendrimers (PGLDs). Hydrophilicity plays a fundamental role in tissue regeneration and fundamental forces that govern the process of cell adhesion and proliferation. In this work, the biocompatible properties and cardiomyocyte proliferation onto PANINTs modified by PGLD are described. PGLDs were immobilized onto PANINTs via surface-initiated anionic ring-opening polymerization of glycidol. The microstructure and morphology of PGLD-PANINTs was determined by X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM), respectively. The cardiac cell growth on the PGLD-PANINTs was investigated. The PGLD-coated PANINTs showed noncytotoxic effects to Chinese hamster ovary cells. It was observed that the application of microcurrent stimulates the differentiation of cardiac cells cultured on PGLD-PANINTs scaffolds. The electroactive and biocompatible results of PGLD-PANINTs observed in this work demonstrate the potential of this nanobiomaterial for the culture of cardiac cells and open the possibility of using this material as a biocompatible electroactive three-dimensional matrix in cardiac tissue engineering.

PMID: 21595714 [PubMed - in process]

   
     
 
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