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| Knoepfler Blog Added to Links
April 9, 2010 at 4:52 PM
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| We are in the midst of cleaning up the aging links that we have posted on the California Stem Cell Report. But first we want to call your attention to a new addition – the Knoepfler Lab Stem Cell Blog.
It is a researcher-oriented blog written by UC Davis Assistant Professor Paul Knoepfler and the folks at his lab. Knoepfler is interested in developing an exchange of information and discussion of | | |
| Age-related molecular genetic changes of murine bone marrow mesenchymal stem cells.
April 9, 2010 at 7:37 AM
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| | Age-related molecular genetic changes of murine bone marrow mesenchymal stem cells. BMC Genomics. 2010 Apr 7;11(1):229 Authors: Wilson A, Shehadeh LA, Yu H, Webster KA ABSTRACT: BACKGROUND: Mesenchymal stem cells (MSC) are pluripotent cells, present in the bone marrow and other tissues that can differentiate into cells of all germ layers and may be involved in tissue maintenance and repair in adult organisms. Because of their plasticity and accessibility these cells are also prime candidates for regenerative medicine. The contribution of stem cell aging to organismal aging is under debate and one theory is that reparative processes deteriorate as a consequence of stem cell aging and/or decrease in number. Age has been linked with changes in osteogenic and adipogenic potential of MSCs. Results: Here we report on changes in global gene expression of cultured MSCs isolated from the bone marrow of mice at ages 2, 8, and 26-months. Microarray analyses revealed significant changes in the expression of more than 8000 genes with stage-specific changes of multiple differentiation, cell cycle and growth factor genes. Key markers of adipog! enesis including lipoprotein lipase, FABP4, and Itm2a displayed age-dependent declines. Expression of the master cell cycle regulators p53 and p21 and growth factors HGF and VEGF also declined significantly at 26 months. These changes were evident despite multiple cell divisions in vitro after bone marrow isolation. Conclusions: The results suggest that MSCs are subject to molecular genetic changes during aging that are conserved during passage in culture. These changes may affect the physiological functions and the potential of autologous MSCs for stem cell therapy. PMID: 20374652 [PubMed - as supplied by publisher] | | |
| Defining adipose tissue-derived stem cells in tissue and in culture.
April 9, 2010 at 6:49 AM
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| | Defining adipose tissue-derived stem cells in tissue and in culture. Histol Histopathol. 2010 Jun;25(6):807-15 Authors: Lin CS, Xin ZC, Deng CH, Ning H, Lin G, Lue TF Adipose tissue-derived stem cells (ADSC) are routinely isolated from the stromal vascular fraction (SVF) of homogenized adipose tissue. Similar to other types of mesenchymal stem cells (MSC), ADSC remain difficult to define due to the lack of definitive cellular markers. Still, many types of MSC, including ADSC, have been shown to reside in a perivascular location, and increasing evidence shows that both MSC and ADSC may in fact be vascular stem cells (VSC). Locally, these cells differentiate into smooth muscle and endothelial cells that are assembled into newly formed blood vessels during angiogenesis and neovasculogenesis. Additionally, MSC or ADSC can also differentiate into tissue cells such as adipocytes in the adipose tissue. Systematically, MSC or ADSC are recruited to injury sites where they participate in the repair/regeneration of the injured tissue. Due to the vasculature's dynamic capacity for growth and multipotential nature for diversification, VSC i! n tissue are individually at various stages and on different paths of differentiation. Therefore, when isolated and put in culture, these cells are expected to be heterogeneous in marker expression, renewal capacity, and differentiation potential. Although this heterogeneity of VSC does impose difficulties and cause confusions in basic science studies, its impact on the development of VSC as a therapeutic cell source has not been as apparent, as many preclinical and clinical trials have reported favorable outcomes. With this understanding, ADSC are generally defined as CD34+CD31- although loss of CD34 expression in culture is well documented. In adipose tissue, CD34 is localized to the intima and adventitia of blood vessels but not the media where cells expressing alpha-smooth muscle actin (SMA) exist. By excluding the intima, which contains the CD34+CD31+ endothelial cells, and the media, which contains the CD34-CD31- smooth muscle cells, it leaves the adventitia as the on! ly possible location for the CD34+ ADSC. In the capillary, CD3! 4 and CD 140b (a pericyte marker) are mutually exclusively expressed, thus suggesting that pericytes are not the CD34+ ADSC. Many other cellular markers for vascular cells, stem cells, and stem cell niche have also been investigated as possible ADSC markers. Particularly the best-known MSC marker STRO-1 has been found either expressed or not expressed in cultured ADSC. In the adipose tissue, STRO-1 appears to be expressed exclusively in the endothelium of certain but not all blood vessels, and thus not associated with the CD34+ ADSC. In conclusion, we believe that ADSC exist as CD34+CD31-CD104b-SMA- cells in the capillary and in the adventitia of larger vessels. In the capillary these cells coexist with pericytes and endothelial cells, both of which are possibly progenies of ADSC (or more precisely VSC). In the larger vessels, these ADSC or VSC exist as specialized fibroblasts (having stem cell properties) in the adventitia. PMID: 20376787 [PubMed - in process] | | |
| [The reconstructive sequence in the 21st century : A reconstructive clockwork.]
April 9, 2010 at 6:49 AM
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| | [The reconstructive sequence in the 21st century : A reconstructive clockwork.] Chirurg. 2010 Apr 9; Authors: Knobloch K, Vogt PM Mathes and Nahai introduced the conventional reconstructive ladder in 1982 to address tissue defects starting with primary and secondary closure of wounds followed by autologous skin grafting. Regional and local pedicled flaps, tissue expansion and free tissue transfer were further steps. Despite enormous achievements and refinements in these techniques, clinical situations and problems occur beyond the scope of these conventional reconstructive measures. Composite tissue allotransplantation (CTA) of partial faces or of unilateral or bilateral forearms and upper arms, are a novel part of transplantation medicine. The initially reported clinical results are encouraging, especially in light of the initial clinical reports of organ transplantation. However, short and long term problems such as potential tumor induction by immunosuppression and chronic rejection must be taken into consideration. Given the fact that patients receiving CTA have already undergone various! reconstructive procedures before, patients often gain tremendous improvement in the quality of life. Robots such as the Da Vinci system for surgeons and the Penelope assistant robot have found their way into the surgical routine. While even microsurgical anastomosis has been accomplished using the Da Vinci system, the total amount of time and resources spent is beyond being practical at present. Regeneration and tissue engineering are of distinct interest in reconstructive surgery. Adipose-derived stem cell transfer is able not only to improve contour defects by volume effects, but also to improve the quality of the overlying skin. Therefore we would propose that these novel techniques, CTA, robotics, regeneration and tissue engineering should be considered as potential future integral cogs in the reconstructive mechanism for the 21st century with the patient being at the centre of the reconstructive efforts. PMID: 20376421 [PubMed - as supplied by publisher] | | |
| The Adipose-derived Stem Cell: Looking Back and Looking Ahead.
April 9, 2010 at 6:49 AM
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| | The Adipose-derived Stem Cell: Looking Back and Looking Ahead. Mol Biol Cell. 2010 Apr 7; Authors: Zuk PA Monitoring Editor: Doug Kellogg In 2002, researchers at UCLA published a manuscript in Molecular Biology of the Cell describing a novel adult stem cell population isolated from adipose tissue - the Adipose-derived Stem Cell or ASC. Because that time, the ASC has gone on to be one of the most popular adult stem cell populations currently being used in the stem cell field. With multi-lineage mesodermal potential and possible ectodermal and endodermal potentials also, the ASC could conceivably be an alternate to pluripotent ES cells in both the lab and in the clinic. In this retrospective article, a historical perspective on the ASC is given together with exciting new applications for the stem cell being considered today. PMID: 20375149 [PubMed - as supplied by publisher] | | |
| Treatment of erectile dysfunction in the obese type 2 diabetic ZDF rat with adipose tissue-derived stem cells.
April 9, 2010 at 6:49 AM
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| | Treatment of erectile dysfunction in the obese type 2 diabetic ZDF rat with adipose tissue-derived stem cells. J Sex Med. 2010 Jan;7(1 Pt 1):89-98 Authors: Garcia MM, Fandel TM, Lin G, Shindel AW, Banie L, Lin CS, Lue TF INTRODUCTION: Erectile dysfunction (ED) is a major complication of type 2 diabetes, and many diabetic men with ED are refractory to common ED therapies. AIM: To determine whether autologous adipose tissue-derived stem cells (ADSCs) injected into the penis of impotent type 2 diabetic rats improve erectile function. MAIN OUTCOME MEASURES: Blood glucose levels, intracavernous pressure (ICP) increase upon cavernous nerve (CN) electrostimulation, and immunohistochemistry. METHODS: Twenty-two male Zucker diabetic fatty (ZDF) rats were used. At 22 weeks of age, all the animals underwent unilateral CN electrostimulation and ICP measurement to confirm impotence. Paragonadal adipose tissue was harvested to procure ADSCs. The impotent animals were randomized to ADSC treatment and sham control groups. At 23 weeks of age, the treatment group animals underwent a penile injection of 1 million ADSCs; the control group animals received vehicle only. Erectile function studies were ! repeated at 26 weeks of age, followed by tissue harvest. RESULTS: The rats developed diabetes within the first 10 weeks of age. At 22 weeks of age, 20 out of the 22 rats presented with ED. The post-treatment ICP increase during CN stimulation and ICP increase/mean arterial pressure were significantly higher in the treatment group compared with controls. Three weeks after injection into the corpus cavernosum, only a small number of BrdU-labeled ADSCs was detectable within corporal tissue of the treatment group. There was a significant increase in neuronal nitric oxide synthase (nNOS) in the penile dorsal nerve and in the number of endothelial cells in the corpora cavernosa of the rats in the treatment group. CONCLUSION: Autologous ADSCs injected into the penis were effective to improve erectile function and to alter the microarchitecture of the corpus cavernosum. Since the number of ADSCs retained in the corpus cavernosum is very small, we postulate that their paracrine func! tion, not trans-differentiation to smooth muscle or endothelia! l cells, is responsible for the improvement in penile function. PMID: 20104670 [PubMed - indexed for MEDLINE] | | |
| Role of neutrophil-derived matrix metalloproteinase-9 in tissue regeneration.
April 9, 2010 at 6:45 AM
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| | Role of neutrophil-derived matrix metalloproteinase-9 in tissue regeneration. Histol Histopathol. 2010 Jun;25(6):765-70 Authors: Heissig B, Nishida C, Tashiro Y, Sato Y, Ishihara M, Ohki M, Gritli I, Rosenkvist J, Hattori K Ischemic tissue regeneration depends on neovascularization, the growth of new blood vessels. Bone marrow (BM)-derived cells, including neutrophils, have been shown to contribute to neovascularization during hind limb ischemia and inflammation. Neutrophils produce a broad array of angiogenic growth factors and proteases, which promote remodeling of arterioles into arteries through proteolytic mechanisms. Matrix metalloproteinases (MMPs) have been shown to play a role in the recruitment of neutrophils to sites of inflammation, which requires the extravascular migration of neutrophils through the extracellular matrix. Neutrophils control critical steps during angiogenesis and neutrophil-derived MMPs can promote neoangiogenesis, and collateral growth and perfusion recovery, in part by liberating vital angiogenic growth factors, including vascular endothelial growth factor-A (VEGF-A). This review focuses on the role of neutrophils as key players in the control of the a! ngiogenic process during ischemic tissue regeneration. Aspects of neutrophil regulation, in particular regulation by its major growth factor granulocyte colony-stimulating factor (G-CSF), the role of the unique, readily available, neutrophil-derived MMP-9, and the functional consequences of this MMP-9 activation for angiogenesis, such as MMP-mediated release of biologically relevant cytokines from the matrix and cell surfaces, will be discussed. PMID: 20376783 [PubMed - in process] | | |
| Expression of stemness markers in mouse parthenogenetic-diploid blastocysts is influenced by slight variation of activation protocol adopted.
April 9, 2010 at 6:45 AM
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| | Expression of stemness markers in mouse parthenogenetic-diploid blastocysts is influenced by slight variation of activation protocol adopted. In Vitro Cell Dev Biol Anim. 2010 Apr 8; Authors: Bianchi E, Geremia R, Sette C The importance of obtaining stem cells through alternative methods has increased progressively in the recent years due to the potential role that embryonic stem (ES) cells play in the field of regenerative medicine. In this regard, generation of parthenogenetic blastocysts allows the production of ethic-free ES cells without the need to manipulate normal embryos. Our work was aimed at clarifying whether variations in the method adopted to generate diploid parthenogenetic blastocysts could determine differences in the quality of blastocysts produced. In vitro development of mouse oocytes activated with three protocols, using Sr(2+) and cytochalasin for different time, was compared with that of in vivo fertilized embryos. We have evaluated the efficiency of blastocyst formation and analysed the expression pattern of the stemness markers OCT4, CDX2, and NANOG. Our results indicate that the yield of diploid parthenogenotes and the segregation of the stemness marker OC! T4 in the developing blastocyst are influenced by the parthenogenetic protocol adopted. Particularly, even if all methods tested allowed the production of blastocysts in vitro, the correct segregation of OCT4 occurred only in blastocysts developed from oocytes concomitantly treated for 4 h with Sr(2+) and cytochalasin D. Our results indicate that the protocol employed to develop parthenogenetic blastocysts in vitro affects the quality of cells in the inner cell mass. PMID: 20376706 [PubMed - as supplied by publisher] | | |
| Comparison of proliferative and multilineage differentiation potentials of cord matrix, cord blood, and bone marrow mesenchymal stem cells.
April 9, 2010 at 6:45 AM
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| | Comparison of proliferative and multilineage differentiation potentials of cord matrix, cord blood, and bone marrow mesenchymal stem cells. Asian J Transfus Sci. 2010 Jan;4(1):14-24 Authors: Shetty P, Cooper K, Viswanathan C BACKGROUND: Hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) are the two widely studied and characterized adult stem cells. Thus far, MSCs were obtained from the bone marrow, which is a painful procedure. Therefore, MSCs from less common sources like cord blood, adipose tissue, tooth pulp, and so on, have been the subject of research. The purpose of this study is to explore the possibility of finding MSCs from a less controversial, easy, and abundant source, such as the umbilical cord, for potential regenerative medicine applications. STUDY DESIGN AND METHODS: Five bone marrow samples (BM), seventy cord blood units (CB), and four umbilical cord matrix (CM) samples have been used for the study. Expanded MSCs were checked for biomarker expression by flow cytometry and were also checked for their differentiation to mesodermal and ectodermal lineages. RESULTS: MSCs could be isolated from 100% BM and CM samples, as compared to only 6% of CB samples. Th! e fold expansion of the mesenchymal stem cells observed in CB (CB-MSCs) was distinctly higher as compared to BM (BM-MSCs) and CM (CM-MSCs). MSCs isolated from all the three sources expressed a characteristic mesenchymal phenotype of CD45 - /vWF - /CD14 - /CD31 - /CD73 + /CD105 + /SSEA4 + /CD29 + /CD44 + /HLAABC +, whereas, the HLA DR was conspicuously absent in CM-MSCs and CB-MSCs. Although osteogenic, chondrogenic, and neural differentiation was observed in MSCs from all sources, adipogenic differentiation was observed only in BM-MSCs. CONCLUSION: CM-MSCs are a dependable source of an unlimited number of MSCs for autologous and allogenic use in regenerative medicine. PMID: 20376261 [PubMed - in process] | | |
| Age-related molecular genetic changes of murine bone marrow mesenchymal stem cells.
April 9, 2010 at 6:45 AM
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| | Age-related molecular genetic changes of murine bone marrow mesenchymal stem cells. BMC Genomics. 2010 Apr 7;11(1):229 Authors: Wilson A, Shehadeh LA, Yu H, Webster KA ABSTRACT: BACKGROUND: Mesenchymal stem cells (MSC) are pluripotent cells, present in the bone marrow and other tissues that can differentiate into cells of all germ layers and may be involved in tissue maintenance and repair in adult organisms. Because of their plasticity and accessibility these cells are also prime candidates for regenerative medicine. The contribution of stem cell aging to organismal aging is under debate and one theory is that reparative processes deteriorate as a consequence of stem cell aging and/or decrease in number. Age has been linked with changes in osteogenic and adipogenic potential of MSCs. Results: Here we report on changes in global gene expression of cultured MSCs isolated from the bone marrow of mice at ages 2, 8, and 26-months. Microarray analyses revealed significant changes in the expression of more than 8000 genes with stage-specific changes of multiple differentiation, cell cycle and growth factor genes. Key markers of adipog! enesis including lipoprotein lipase, FABP4, and Itm2a displayed age-dependent declines. Expression of the master cell cycle regulators p53 and p21 and growth factors HGF and VEGF also declined significantly at 26 months. These changes were evident despite multiple cell divisions in vitro after bone marrow isolation. Conclusions: The results suggest that MSCs are subject to molecular genetic changes during aging that are conserved during passage in culture. These changes may affect the physiological functions and the potential of autologous MSCs for stem cell therapy. PMID: 20374652 [PubMed - as supplied by publisher] | | |
| Human melanocytes can be isolated, propagated and expanded from plucked anagen hair follicles.
April 9, 2010 at 6:45 AM
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| | Human melanocytes can be isolated, propagated and expanded from plucked anagen hair follicles. Exp Dermatol. 2010 Mar 30; Authors: Dieckmann C, Milkova L, Hunziker T, Emmendörffer A, Simon JC Please cite this paper as: Human melanocytes can be isolated, propagated and expanded from plucked anagen hair follicles. Experimental Dermatology 2010. Abstract: Herein, we report a technically simple method for isolation and culture of human follicular melanocytes based on explant cultures of epilated hair follicles. This technique does not require any surgical intervention and allows the isolation and cultivation of follicular melanocytes from a comparatively small amount of raw material. Generally, 30-60 human anagen hair follicles have been plucked from the scalp of healthy donors and cultivated under low oxygen pressure (5%). After a short period of time cells of various types were growing out from the outer root sheath (ORS) of the hair follicles. Under the selected culture conditions, most of the cells other than melanocytes have been eliminated and a nearly 100% pure population of melanocytes has been achieved, as confirmed by immunohistochemical analyses! for melanocyte-specific markers, for example, Tyrosinase-1, S-100 and premelanosomal antigens. These melanocytes derived from the ORS were proliferating for up to 2 months. PMID: 20374294 [PubMed - as supplied by publisher] | | |
| Wnt/beta-catenin signaling in oral tissue development and disease.
April 9, 2010 at 6:45 AM
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| | Wnt/beta-catenin signaling in oral tissue development and disease. J Dent Res. 2010 Apr;89(4):318-30 Authors: Liu F, Millar SE The Wnt/beta-catenin signaling pathway is one of several key conserved intercellular signaling pathways in animals, and plays fundamental roles in the proliferation, regeneration, differentiation, and function of many cell and tissue types. This pathway is activated in a dynamic manner during the morphogenesis of oral organs, including teeth, taste papillae, and taste buds, and is essential for these processes to occur normally. Conversely, forced activation of Wnt/beta-catenin signaling promotes the formation of ectopic teeth and taste papillae. In this review, we discuss our current understanding of the roles of Wnt/beta-catenin signaling in oral tissue development and in related human diseases, and the potential of manipulating this pathway for therapeutic purposes. PMID: 20200414 [PubMed - indexed for MEDLINE] | | |
| Development of Electrospun Three-arm Star Poly(epsilon-caprolactone) Meshes for Tissue Engineering Applications.
April 9, 2010 at 6:08 AM
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| | Development of Electrospun Three-arm Star Poly(epsilon-caprolactone) Meshes for Tissue Engineering Applications. Macromol Biosci. 2010 Apr 6; Authors: Puppi D, Detta N, Piras AM, Chiellini F, Clarke DA, Reilly GC, Chiellini E We have developed three-dimensional electrospun microfibrous meshes of a novel star branched three-arm poly(epsilon-caprolactone) (*PCL) as potential scaffolds for tissue engineering applications. The processing conditions required to obtain uniform fibers were optimized by studying their influence on fiber morphology and size. Polymer molecular weight and solution feed rate influenced both the mesh microstructure and the tensile properties of the developed mats. Electrospun samples were also tested for their mechanical properties in wet conditions, showing higher yield strength and strain in comparison to that observed in dry conditions. Cell culture experiments employing MC3T3-E1 osteoblast like cells showed good cell viability adhesion and collagen production on the *PCL scaffolds. PMID: 20376838 [PubMed - as supplied by publisher] | | |
| [The reconstructive sequence in the 21st century : A reconstructive clockwork.]
April 9, 2010 at 6:08 AM
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| | [The reconstructive sequence in the 21st century : A reconstructive clockwork.] Chirurg. 2010 Apr 9; Authors: Knobloch K, Vogt PM Mathes and Nahai introduced the conventional reconstructive ladder in 1982 to address tissue defects starting with primary and secondary closure of wounds followed by autologous skin grafting. Regional and local pedicled flaps, tissue expansion and free tissue transfer were further steps. Despite enormous achievements and refinements in these techniques, clinical situations and problems occur beyond the scope of these conventional reconstructive measures. Composite tissue allotransplantation (CTA) of partial faces or of unilateral or bilateral forearms and upper arms, are a novel part of transplantation medicine. The initially reported clinical results are encouraging, especially in light of the initial clinical reports of organ transplantation. However, short and long term problems such as potential tumor induction by immunosuppression and chronic rejection must be taken into consideration. Given the fact that patients receiving CTA have already undergone various! reconstructive procedures before, patients often gain tremendous improvement in the quality of life. Robots such as the Da Vinci system for surgeons and the Penelope assistant robot have found their way into the surgical routine. While even microsurgical anastomosis has been accomplished using the Da Vinci system, the total amount of time and resources spent is beyond being practical at present. Regeneration and tissue engineering are of distinct interest in reconstructive surgery. Adipose-derived stem cell transfer is able not only to improve contour defects by volume effects, but also to improve the quality of the overlying skin. Therefore we would propose that these novel techniques, CTA, robotics, regeneration and tissue engineering should be considered as potential future integral cogs in the reconstructive mechanism for the 21st century with the patient being at the centre of the reconstructive efforts. PMID: 20376421 [PubMed - as supplied by publisher] | | |
| The Impact of Contact Angle on the Biocompatibility of Biomaterials.
April 9, 2010 at 6:08 AM
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| | The Impact of Contact Angle on the Biocompatibility of Biomaterials. Optom Vis Sci. 2010 Apr 1; Authors: Menzies KL, Jones L Biomaterials may be defined as artificial materials that can mimic, store, or come into close contact with living biological cells or fluids and are becoming increasingly popular in the medical, biomedical, optometric, dental, and pharmaceutical industries. Within the ophthalmic industry, the best example of a biomaterial is a contact lens, which is worn by approximately 125 million people worldwide. For biomaterials to be biocompatible, they cannot illicit any type of unfavorable response when exposed to the tissue they contact. A characteristic that significantly influences this response is that related to surface wettability, which is often determined by measuring the contact angle of the material. This article reviews the impact of contact angle on the biocompatibility of tissue engineering substrates, blood-contacting devices, dental implants, intraocular lenses, and contact lens materials. PMID: 20375749 [PubMed - as supplied by publisher] | | |
| Mid-term effect of stem cells combined with transmyocardial degradable stent on swine model of acute myocardial infarction.
April 9, 2010 at 6:08 AM
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| | Mid-term effect of stem cells combined with transmyocardial degradable stent on swine model of acute myocardial infarction. Coron Artery Dis. 2010 Mar 31; Authors: Luan Y, Liu XC, Zhang GW, Shi RF, Zhao XB, Zhao CH, Liu TJ, Lü F, Yang Q, He GW BACKGROUND: We aimed to confirm the mid-term results of the new method combined with bone marrow-derived mesenchymal stem cells (MSCs) transplantation and transmyocardial drilling revascularization (TMDR) with degradable stent incorporated with basic fibroblast growth factor and heparin. METHODS: The miniswine underwent acute myocardial infarction by ligation of the left anterior descending coronary artery. Transmyocardial channels with 3.5 mm diameter (TMDR) were made by mechanical drilling in the infarction territory and basic fibroblast growth factor stents were implanted into the channels. Animals were randomly divided into the following four groups (n=6 in each): control; II: MSCs implantation; III: TMDR+stent implantation; IV: TMDR+stent implantation+MSCs implantation. Three months postoperatively, ECG-gated single photon emission computed tomography, histopathological examination, and reverse transcription-polymerase chain reaction were carried out. RESULTS! : Left ventricular ejection fraction and myocardial perfusion were significantly improved in group IV than that in other groups (P<0.05). Compared with other groups, vessel density was augmented and cell apoptosis was reduced in group IV (P<0.01). Reverse transcription-polymerase chain reaction results showed that the expression levels of von Willebrand factor, transforming growth factor-beta3, vascular endothelial growth factor, and interleukin-1beta were much higher in group IV than that in other groups (P<0.05). CONCLUSION: Three months after operation, MSCs transplantation combined with TMDR and degradable stent significantly improved cardiac function, enhanced neovascular density, reduced infarcted size, improved ventricular remodeling, and reduced cardiac myocyte apoptosis, and therefore provides strong information for clinical trial. PMID: 20375694 [PubMed - as supplied by publisher] | | |
| High performance shape memory polymer networks based on rigid nanoparticle cores.
April 9, 2010 at 6:08 AM
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| | High performance shape memory polymer networks based on rigid nanoparticle cores. Proc Natl Acad Sci U S A. 2010 Apr 7; Authors: Xu J, Song J Smart materials that can respond to external stimuli are of widespread interest in biomedical science. Thermal-responsive shape memory polymers, a class of intelligent materials that can be fixed at a temporary shape below their transition temperature (T(trans)) and thermally triggered to resume their original shapes on demand, hold great potential as minimally invasive self-fitting tissue scaffolds or implants. The intrinsic mechanism for shape memory behavior of polymers is the freezing and activation of the long-range motion of polymer chain segments below and above T(trans), respectively. Both T(trans) and the extent of polymer chain participation in effective elastic deformation and recovery are determined by the network composition and structure, which are also defining factors for their mechanical properties, degradability, and bioactivities. Such complexity has made it extremely challenging to achieve the ideal combination of a T(trans) slightly above phys! iological temperature, rapid and complete recovery, and suitable mechanical and biological properties for clinical applications. Here we report a shape memory polymer network constructed from a polyhedral oligomeric silsesquioxane nanoparticle core functionalized with eight polyester arms. The cross-linked networks comprising this macromer possessed a gigapascal-storage modulus at body temperature and a T(trans) between 42 and 48 degrees C. The materials could stably hold their temporary shapes for > 1 year at room temperature and achieve full shape recovery </= 51 degrees C in a matter of seconds. Their versatile structures allowed for tunable biodegradability and biofunctionalizability. These materials have tremendous promise for tissue engineering applications. PMID: 20375285 [PubMed - as supplied by publisher] | | |
| Phosphopantetheinyl Transferase-Catalyzed Formation of Bioactive Hydrogels for Tissue Engineering.
April 9, 2010 at 6:08 AM
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| | Phosphopantetheinyl Transferase-Catalyzed Formation of Bioactive Hydrogels for Tissue Engineering. J Am Chem Soc. 2010 Apr 7; Authors: Mosiewicz KA, Johnsson K, Lutolf MP Synthetic bioactive hydrogels have been widely recognized as key elements of emerging strategies to engineer tissues. However, the current shortage of highly specific and biocompatible methods to form and functionalize these materials hampers their wide pharmaceutical and medical use. In particular, enzymatic reactions are underexplored for the synthesis of bioactive hydrogels. Here, we present an approach by which phosphopantetheinyl transferase (PPTase), a small (16.2 kDa) enzyme that plays a key role in the biosynthesis of many natural products, was employed to catalyze covalent cross-linking of poly(ethylene glycol) (PEG)-based hydrogels. Gels were formed within minutes under physiological conditions by mixing two aqueous precursors containing multiarm PEG macromers end-functionalized with the PPTase substrate Coenzyme A (CoA) and a genetically engineered dimer of a carrier protein. The physicochemical properties of this new class of biomaterials were characte! rized. Bioactive hydrogels were produced by covalent incorporation of a CoA-functionalized cell adhesion peptide (RGDS), resulting in specific adhesion of primary fibroblasts on the hydrogel surfaces. 3D encapsulation of cells resulted in high cell viability (ca. 95%) and single cell migration over long distances within RGDS-modified gels. PMID: 20373804 [PubMed - as supplied by publisher] | | |
| Directed growth of fibroblasts into three dimensional micropatterned geometries via self-assembling scaffolds.
April 9, 2010 at 6:08 AM
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| | Directed growth of fibroblasts into three dimensional micropatterned geometries via self-assembling scaffolds. Biomaterials. 2010 Mar;31(7):1683-90 Authors: Jamal M, Bassik N, Cho JH, Randall CL, Gracias DH We describe the use of conventional photolithography to construct three dimensional (3D) thin film scaffolds and direct the growth of fibroblasts into three distinct and anatomically relevant geometries: cylinders, spirals and bi-directionally folded sheets. The scaffolds were micropatterned as two dimensional sheets which then spontaneously assembled into specific geometries upon release from the underlying substrate. The viability of fibroblasts cultured on these self-assembling scaffolds was verified using fluorescence microscopy; cell morphology and spreading were studied using scanning electron microscopy. We demonstrate control over scaffold size, radius of curvature and folding pitch, thereby enabling an attractive approach for investigating the effects of these 3D geometric factors on cell behaviour. PMID: 20022106 [PubMed - indexed for MEDLINE] | | |
| The promotion of endothelial progenitor cells recruitment by nerve growth factors in tissue-engineered blood vessels.
April 9, 2010 at 6:08 AM
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| | The promotion of endothelial progenitor cells recruitment by nerve growth factors in tissue-engineered blood vessels. Biomaterials. 2010 Mar;31(7):1636-45 Authors: Zeng W, Yuan W, Li L, Mi J, Xu S, Wen C, Zhou Z, Xiong J, Sun J, Ying D, Yang M, Li X, Zhu C Endothelial progenitor cells (EPCs) mobilization and homing are critical to the development of an anti-thrombosis and anti-stenosis tissue-engineered blood vessel. The growth and activation of blood vessels are supported by nerves. We investigated whether nerve growth factors (NGF) can promote EPCs mobilization and endothelialization of tissue-engineered blood vessels. In vitro, NGF promoted EPCs to form more colonies, stimulated human EPCs to differentiate into endothelial cells, and significantly enhanced EPCs migration. Flow cytometric analysis revealed that NGF treatment increased the number of EPCs in the peripheral circulation of C57BL/6 mice. Furthermore, the treatment of human EPCs with NGF facilitated their homing into wire-injured carotid arteries after injection into mice. Decellularized rat blood vessel matrix was incubated with EDC cross-linked collagen and bound to NGF protein using the bifunctional coupling agent N-succinmidyl3-(2-pyridyldit-hio) pr! opionate (SPDP). The NGF-bound tissue-engineered blood vessel was implanted into rat carotid artery for 1 week and 1 month. NGF-bound blood vessels possessed significantly higher levels of endothelialization and patency than controls did. These results demonstrated that NGF can markedly increase EPCs mobilization and homing to vascular grafts. Neurotrophic factors such as NGF have a therapeutic potential for the construction of tissue-engineered blood vessels in vivo. PMID: 20006381 [PubMed - indexed for MEDLINE] | | |
| Physiologic compliance in engineered small-diameter arterial constructs based on an elastomeric substrate.
April 9, 2010 at 6:08 AM
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| | Physiologic compliance in engineered small-diameter arterial constructs based on an elastomeric substrate. Biomaterials. 2010 Mar;31(7):1626-35 Authors: Crapo PM, Wang Y Compliance mismatch is a significant challenge to long-term patency in small-diameter bypass grafts because it causes intimal hyperplasia and ultimately graft occlusion. Current engineered grafts are typically stiff with high burst pressure but low compliance and low elastin expression. We postulated that engineering small arteries on elastomeric scaffolds under dynamic mechanical stimulation would result in strong and compliant arterial constructs. This study compares properties of engineered arterial constructs based on biodegradable polyester scaffolds composed of either rigid poly(lactide-co-glycolide) (PLGA) or elastomeric poly(glycerol sebacate) (PGS). Adult baboon arterial smooth muscle cells (SMCs) were cultured in vitro for 10 days in tubular, porous scaffolds. Scaffolds were significantly stronger after culture regardless of material, but the elastic modulus of PLGA constructs was an order of magnitude greater than that of porcine carotid arteries and PG! S constructs. Deformation was elastic in PGS constructs and carotid arteries but plastic in PLGA constructs. Compliance of arteries and PGS constructs were equivalent at pressures tested. Altering scaffold material from PLGA to PGS significantly decreased collagen content and significantly increased insoluble elastin content in constructs without affecting soluble elastin concentration in the culture medium. PLGA constructs contained no appreciable insoluble elastin. This research demonstrates that: (1) substrate stiffness directly affects in vitro tissue development and mechanical properties; (2) rigid materials likely inhibit elastin incorporation into the extracellular matrix of engineered arterial tissues; and (3) grafts with physiologic compliance and significant elastin content can be engineered in vitro after only days of cell culture. PMID: 19962188 [PubMed - indexed for MEDLINE] | | |
| Design of prevascularized three-dimensional cell-dense tissues using a cell sheet stacking manipulation technology.
April 9, 2010 at 6:08 AM
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| | Design of prevascularized three-dimensional cell-dense tissues using a cell sheet stacking manipulation technology. Biomaterials. 2010 Mar;31(7):1646-54 Authors: Sasagawa T, Shimizu T, Sekiya S, Haraguchi Y, Yamato M, Sawa Y, Okano T To survive three-dimensional (3-D) cell-dense thick tissues after transplantation, the improvements of hypoxia, nutrient insufficiency, and accumulation of waste products are required. This study presents a strategy for the initiation of prevascular networks in a 3-D tissue construct by sandwiching endothelial cells between the cell sheets. For obtaining a stable stacked cell sheet construct, a sophisticated 3-D cell sheet manipulation system using temperature-responsive culture dishes and a cell sheet manipulator was developed. When sparsely cultured human umbilical vein endothelial cells (HUVECs) were sandwiched between two myoblast sheets, the inserted HUVECs sprouted and formed network structures in vitro. Additionally, when myoblast sheets and HUVECs were alternately sandwiched, endothelial cell connections through the layers and capillary-like structures were found in a five-layer construct. Moreover, the endothelial networks in the five-layer myoblast sheet! construct were observed to connect to the host vessels after transplantation into the subcutaneous tissues of nude rats, resulted in a neovascularization that allow the graft to survive. These results indicated that the prevascularized myoblast sheet constructs could induce functional anastomosis. Consequently, our prevascularizing method using a cell sheet stacking manipulation technology provides a substantial advance for developing various types of three-dimensional tissues and contributes to regenerative medicine. PMID: 19962187 [PubMed - indexed for MEDLINE] | | |
| [In vitro trials with single and co-cultures of osteoblasts and endothelial cells : evaluation of new biomaterials for bone reconstruction and regeneration]
April 9, 2010 at 6:08 AM
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| | [In vitro trials with single and co-cultures of osteoblasts and endothelial cells : evaluation of new biomaterials for bone reconstruction and regeneration] Orthopade. 2009 Nov;38(11):1020-8 Authors: Unger RE, Halstenberg S, Günther H, Sartoris A, Brochhausen C, Kirkpatrick CJ Many different types of bone substitute biomaterials are being developed for different applications in the body. The current dogma is that if osteoblasts and endothelial cells grow and exhibit normal cell functions on these materials in vitro as single cultures or in co-cultures, then the biomaterials are suitable for implantation for bone reconstruction and regeneration. Generally, only in vivo animal studies will prove whether this is the case. However, in vitro studies offer a good pre-screening and selection basis to evaluate the biocompatibility of novel biomaterials prior to animal studies. Multicell type co-culture systems hold a great promise for the future. PMID: 19838668 [PubMed - indexed for MEDLINE] | | |
| [Biomaterial for autologous chondrocyte transplantation]
April 9, 2010 at 6:08 AM
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| | [Biomaterial for autologous chondrocyte transplantation] Orthopade. 2009 Nov;38(11):1045-52 Authors: Marlovits S, Aldrian S, Tichy B, Albrecht C, Nürnberger S Autologous chondrocyte transplantation (ACT) is a cell-based biological cartilage repair procedure for the regeneration of injured articular cartilage. The further modification of classical ACT to matrix-associated autologous chondrocyte transplantation (MACT) includes the use of biomaterials as cell carriers and has biological and surgical advantages. The use of biomaterials as cell carriers for chondrocytes requires the analysis of cell culture conditions, cell-cell and cell-matrix interactions and also the determination of chondrocytic differentiation. The biomaterials used preserve the specific cellular architecture of chondrocytes and the combination of cultivated cells with biomaterials leads to the formation of cartilage-specific extracellular matrix components. PMID: 19789853 [PubMed - indexed for MEDLINE] | | |
| [Experimental studies on anti-mouse hepatocellular carcinoma effects of cisplatin combined with exosomes]
April 9, 2010 at 6:08 AM
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| | [Experimental studies on anti-mouse hepatocellular carcinoma effects of cisplatin combined with exosomes] Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2009 Jan;25(1):49-52 Authors: Wang SH, Shen Y, Li J, Xiang ZW, Fan WK, Chen L AIM: To study the anti-tumor effects and mechanisms of cisplatin(DDP) combined with exosomes. METHODS: The cell-growth inhibition of DDP on H(22); cells was analyzed by MTT assay.The mice were immunized by H(22); cell-derived exosomes. The exosomes elicited CTL-specific cytotoxicity and DDP enhanced cytotoxicity in combination with CTL were detected by (3)H-TdR release assay. The effect of DDP on mRNA and protein levels of Fas in H(22); was analyzed using RT-PCR and Western blot.The expression of FasL on spleen lymphocyte was determined by RT-PCR. BALB/c mice inoculated with hepatoma carcinoma cell line H(22); were used as tumor models.The mice received exosomes solely or in combination with DDP.The survival of the mice was observed. RESULTS: DDP inhibited H(22); cell in a dose-dependant manner. The exosomes elicited CTL-specific cytotoxicity was enhanced by DDP (P<0.05). RT-PCR and Western blot showed Fas increased gradually after administering DDP on H(22); c! ells.RT-PCR also indicated the mRNA level of FasL on mice spleen lymphocyte increased after immunized by exosomes. Compared with other groups, the combination group(DDP plus exosomes)could statistically prolong the survival time (P<0.05). CONCLUSION: The therapy of DDP combined with exosomes had significant synergistic effect against tumor. The mechanism of synergistic effect includes enhancement of CTL activity. PMID: 19126388 [PubMed - indexed for MEDLINE] | | | | 
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