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| CIRM Comments on New NIH Disclosure Rules
May 26, 2010 at 12:05 AM
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| Don Gibbons, chief communications officer for the California stem cell agency, filed this comment today on our post, "Disclosure Proposal Likely to Affect CIRM."
"Casual readers of your posts will take away the notion that NIH is now requiring scientist peer reviewers to post their financial conflicts on the web. That is not true. Existing NIH policy, which is mirrored by CIRM policy, as well as | | |
| Recent advances in liver stem cell therapy.
May 25, 2010 at 8:47 AM
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| | Recent advances in liver stem cell therapy. Curr Opin Gastroenterol. 2010 May 20; Authors: Kisseleva T, Gigante E, Brenner DA PURPOSE OF REVIEW: Patients with liver cirrhosis often require liver transplantation, which remains the only effective treatment of the end-stage cirrhosis. Here we briefly summarize the current concepts in treatment of liver diseases based on the transplantation of intrahepatic liver cells, capable of repopulating the injured liver. These cells include hepatocytes, oval cells (bipotential intrahepatic progenitor cells), bone marrow hematopoietic and mesenchymal stem cells, and induced pluripotent stem (iPS) cells. RECENT FINDINGS: Although liver transplantation remains the only conventional treatment, liver cell transplantation is an experimental procedure which has been successfully used in clinical trials in patients with acute liver failure, chronic liver disease with end-stage cirrhosis. Extraordinary progress has been made in the field of hepatic progenitors and iPS. Liver precursor cells (oval cells) are recognized as bipotential precursor cells in the dama! ged liver. They can rapidly proliferate, change their cellular composition, and differentiate into hepatocytes and cholangiocytes to compensate for the cellular loss and maintain liver homeostasis in animal models of liver injury. Similarly, iPS are somatic cells obtained from patients and differentiated into hepatocytes in vitro. Future studies of iPS are designed to develop of specific conditions to expand and in vitro differentiate somatic cells into functionally mature liver cells. SUMMARY: The current review defines and discusses different populations of hepatic cells which can be potentially used for liver cell transplantation to advance the therapy of hepatic cirrhosis. PMID: 20495456 [PubMed - as supplied by publisher] | | |
| [Cerebral plasticity: From bench to bedside in stroke treatment.]
May 25, 2010 at 8:47 AM
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| | [Cerebral plasticity: From bench to bedside in stroke treatment.] Rev Med Interne. 2010 May 20; Authors: Deroide N, Nih LR, Tran Dinh RY, Lévy B, Kubis N It has long been believed that cerebral lesions were irreversible in the adult human brain. However, the spontaneous improvement in functional outcome observed in the following weeks after cerebral ischemia suggests plasticity phenomenons involving postischemic neuronal network reorganization. Regarding the large prevalence of stroke in industrialized countries, and the few available treatments, the understanding of cerebral plasticity has become an important issue but also a potential source of new therapeutic approaches in stroke. Thus, "constraint induced therapy" and repetitive transcranial magnetic stimulation (rTMS) are based on the concept of local but also remote consequences of the ischemic focal lesion. Cell-therapy is based on the capacity of stem cells to respond to hypoxic signals and adapt their phenotype to the host organ, but above all to release cytokines locally and boost endogeneous repair mechanisms. We could consider to perform in the future a! sequential treatment with fibrinolysis, stem cell therapy, repetitive transcranial magnetic stimulation and constraint-induced therapy in the same patient. PMID: 20494495 [PubMed - as supplied by publisher] | | |
| Mesenchymal Stem Cells Overexpressing Ephrin-B2 Rapidly Adopt an Early Endothelial Phenotype with Simultaneous Reduction of Osteogenic Potential.
May 25, 2010 at 8:47 AM
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| | Mesenchymal Stem Cells Overexpressing Ephrin-B2 Rapidly Adopt an Early Endothelial Phenotype with Simultaneous Reduction of Osteogenic Potential. Tissue Eng Part A. 2010 May 22; Authors: Duffy GP, D'Arcy S, Ahsan T, Nerem RM, O'Brien T, Barry F Restoration of the vascular supply to ischemic tissues is of high clinical relevance, and proangiogenic therapies aim to reduce morbidity and mortality rates associated with the onset of cardiovascular disease. Stem cell therapy has been proposed as a potentially useful proangiogenic therapy. Mesenchymal stem cells (MSCs) have been shown to be proangiogenic and produce a number of cytokines involved in vessel development and maturation. Preclinical studies have reported increased angiogenesis after MSC delivery to the heart, and similar outcomes have been reported in recent clinical trials. Stem-cell-mediated neovascularization has been augmented by genetic modification with overexpression of angiogenic cytokines, including vascular endothelial growth factor (VEGF) and platelet-derived growth factor, showing promising results. In this study we aimed to enhance the proangiogenic capability of MSCs. MSCs were genetically modified to overexpress a versatile molecule,! Ephrin-B2, involved in tissue morphogenesis and vascular development to enhance inherent neovascularization potential. Using nucleofection, Ephrin-B2 was transiently overexpressed on the cell surface of MSCs to recapitulate embryonic signaling and promote neovascularization. Ephrin-B2-expressing MSCs adopted an early endothelial phenotype under endothelial cell culture conditions increasing expression of von Willebrand factor and VEGF-Receptor 2. The cells had an increased ability to form vessel-like structures, produce VEGF, and incorporate into newly formed endothelial cell structures. These data indicate that MSCs expressing Ephrin-B2 represent a novel proangiogenic cell source to promote neovascularization in ischemic tissues. PMID: 20491587 [PubMed - as supplied by publisher] | | |
| Manserin, a secretogranin II-derived peptide, distributes in the rat endocrine pancreas colocalized with islet-cell specific manner.
May 25, 2010 at 6:32 AM
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| | Manserin, a secretogranin II-derived peptide, distributes in the rat endocrine pancreas colocalized with islet-cell specific manner. Histochem Cell Biol. 2010 May 22; Authors: Tano K, Oyabu A, Tashiro Y, Kamada N, Narita N, Nasu F, Narita M Manserin is a recently characterized 40-amino acid neuropeptide derived from secretogranin II, a protein belonging to the chromogranin family. Although the physiological roles of manserin have not been elucidated to date, manserin has been shown to distribute in not only the brain but also the endocrine system such as the pituitary and adrenal glands, suggesting its role in the endocrine system. The present study aimed to explore the occurrence and distribution of manserin in the rat pancreas using an immunohistochemical technique with a polyclonal antibody against rat manserin. Immunoreactivity for manserin was readily detected in almost whole islets of Langerhans whereas not at all in the exocrine pancreas. Manserin-expressing cells were not colocalized with the glucagon-secreting cells (alpha cells), whereas they colocalized with insulin-secreting cells (beta cells) and somatostatin-secreting cells (delta cells), although their intracellular distribution was di! fferent. These results indicate that manserin, occurring in the endocrine pancreas, may have a potential role in the endocrine system. PMID: 20495819 [PubMed - as supplied by publisher] | | |
| Transcriptional regulation of endochondral ossification by HIF-2alpha during skeletal growth and osteoarthritis development.
May 25, 2010 at 6:32 AM
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| | Transcriptional regulation of endochondral ossification by HIF-2alpha during skeletal growth and osteoarthritis development. Nat Med. 2010 May 23; Authors: Saito T, Fukai A, Mabuchi A, Ikeda T, Yano F, Ohba S, Nishida N, Akune T, Yoshimura N, Nakagawa T, Nakamura K, Tokunaga K, Chung UI, Kawaguchi H Chondrocyte hypertrophy followed by cartilage matrix degradation and vascular invasion, characterized by expression of type X collagen (COL10A1), matrix metalloproteinase-13 (MMP-13) and vascular endothelial growth factor (VEGF), respectively, are central steps of endochondral ossification during normal skeletal growth and osteoarthritis development. A COL10A1 promoter assay identified hypoxia-inducible factor-2alpha (HIF-2alpha, encoded by EPAS1) as the most potent transactivator of COL10A1. HIF-2alpha enhanced promoter activities of COL10A1, MMP13 and VEGFA through specific binding to the respective hypoxia-responsive elements. HIF-2alpha, independently of oxygen-dependent hydroxylation, was essential for endochondral ossification of cultured chondrocytes and embryonic skeletal growth in mice. HIF-2alpha expression was higher in osteoarthritic cartilages versus nondiseased cartilages of mice and humans. Epas1-heterozygous deficient mice showed resistance to oste! oarthritis development, and a functional single nucleotide polymorphism (SNP) in the human EPAS1 gene was associated with knee osteoarthritis in a Japanese population. The EPAS1 promoter assay identified RELA, a nuclear factor-kappaB (NF-kappaB) family member, as a potent inducer of HIF-2alpha expression. Hence, HIF-2alpha is a central transactivator that targets several crucial genes for endochondral ossification and may represent a therapeutic target for osteoarthritis. PMID: 20495570 [PubMed - as supplied by publisher] | | |
| The reverse Warburg effect: Glycolysis inhibitors prevent the tumor promoting effects of caveolin-1 deficient cancer associated fibroblasts.
May 25, 2010 at 6:32 AM
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| | The reverse Warburg effect: Glycolysis inhibitors prevent the tumor promoting effects of caveolin-1 deficient cancer associated fibroblasts. Cell Cycle. 2010 May 23;9(10) Authors: Bonuccelli G, Whitaker-Menezes D, Castello-Cros R, Pavlides S, Pestell RG, Fatatis A, Witkiewicz AK, Vander Heiden MG, Migneco G, Chiavarina B, Frank PG, Capozza F, Flomenberg N, Martinez-Outschoorn UE, Sotgia F, Lisanti MP We and others have previously identified a loss of stromal caveolin-1 (Cav-1) in cancer-associated fibroblasts (CAFs) as a powerful single independent predictor of breast cancer patient tumor recurrence, metastasis, tamoxifen-resistance and poor clinical outcome. However, it remains unknown how loss of stromal Cav-1 mediates these effects clinically. To mechanistically address this issue, we have now generated a novel human tumor xenograft model. In this two-component system, nude mice are co-injected with (i) human breast cancer cells (MDA-MB-231), and (ii) stromal fibroblasts (wild-type (WT) versus Cav-1 (-/-) deficient). This allowed us to directly evaluate the effects of a Cav-1 deficiency solely in the tumor stromal compartment. Here, we show that Cav-1-deficient stromal fibroblasts are sufficient to promote both tumor growth and angiogenesis, and to recruit Cav-1 (+) micro-vascular cells. Proteomic analysis of Cav-1-deficient stromal fibroblasts indicates th! at these cells upregulate the expression of glycolytic enzymes, a hallmark of aerobic glycolysis (the Warburg effect). Thus, Cav-1-deficient stromal fibroblasts may contribute towards tumor growth and angiogenesis, by providing energy-rich metabolites in a paracrine fashion. We have previously termed this new idea the "Reverse Warburg Effect". In direct support of this notion, treatment of this xenograft model with glycolysis inhibitors functionally blocks the positive effects of Cav-1-deficient stromal fibroblasts on breast cancer tumor growth. Thus, pharmacologically-induced metabolic restriction (via treatment with glycolysis inhibitors) may be a promising new therapeutic strategy for breast cancer patients that lack stromal Cav-1 expression. We also identify the stromal expression of PKM2 and LDH-B as new candidate biomarkers for the "Reverse Warburg Effect" or "Stromal-Epithelial Metabolic Coupling" in human breast cancers. PMID: 20495363 [PubMed - as supplied by publisher] | | |
| Regulation of corneal inflammation by neutrophil-dependent cleavage of keratan sulfate proteoglycans as a model for breakdown of the chemokine gradient.
May 25, 2010 at 6:32 AM
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| | Regulation of corneal inflammation by neutrophil-dependent cleavage of keratan sulfate proteoglycans as a model for breakdown of the chemokine gradient. J Leukoc Biol. 2010 May 21; Authors: Carlson EC, Sun Y, Auletta J, Kao WW, Liu CY, Perez VL, Pearlman E Keratocan and lumican are small, leucine-rich repeat KSPGs in the extracellular matrix (ECM) of the mammalian cornea, whose primary role is to maintain corneal transparency. In the current study, we examined the role of these proteoglycans in the breakdown of the chemokine gradient and resolution of corneal inflammation. LPS was injected into the corneal stroma of C57BL/6 mice, and corneal extracts were examined by immunoblot analysis. We found reduced expression of the 52-kD keratocan protein after 6 h and conversely, increased expression of 34/37 kD immunoreactive products. Further, appearance of the 34/37-kD proteins was dependent on neutrophil infiltration to the cornea, as the appearance of these products was coincident with neutrophil infiltration, and the 34/37-kD products were not detected in explanted corneas or in CXCR2(-/-) corneas with deficient neutrophil recruitment. Furthermore, the 34/37-kD products and CXCL1/KC were detected in the anterior chambe! r, into which the corneal stroma drains; and CXCL1/KC was elevated significantly in keratocan(-/- )and lumican(-/-) mice. Together, these findings indicate that the inflammatory response in the cornea is regulated by proteoglycan/CXCL1 complexes, and their diffusion into the anterior chamber is consistent with release of a chemokine gradient and resolution of inflammation. PMID: 20495072 [PubMed - as supplied by publisher] | | |
| Towards stem cell replacement therapies for Parkinson's disease.
May 25, 2010 at 6:32 AM
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| | Towards stem cell replacement therapies for Parkinson's disease. Biochem Biophys Res Commun. 2010 May 21;396(1):152-156 Authors: Arenas E Current therapeutic approaches for Parkinson's disease (PD) provide symptomatic relief but none of them change the course of disease. There is therefore a clear need for regenerative and cell replacement therapies (CRT). However, CRT faces several important challenges. First, the main symptoms of PD result from the loss of midbrain dopamine (DA) neurons, but other cell types are also affected. Second, transplantation of human ventral midbrain tissue from aborted fetuses has lead to proof of principle that CRT may work, however, it has also pointed out to important patient-, surgery- and cell preparation-related variables, which need to be improved. Third, while some patients have developed dyskinesias and, with time, Lewy bodies in the grafted cells, other patients have experienced remarkable improvement and have been able to stop their medication. Is there a case for PD CRT today? What is the possible contribution of stem cells to CRT? In this review, I will disc! uss what we learned from clinical trials using fetal tissue grafts, recent progress in the development of human stem cell-derived-DA neurons for CRT, and some of the issues that need to be solved in order to develop stem cells as tools for PD CRT. PMID: 20494130 [PubMed - as supplied by publisher] | | |
| Toward delivery of multiple growth factors in tissue engineering.
May 25, 2010 at 6:32 AM
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| | Toward delivery of multiple growth factors in tissue engineering. Biomaterials. 2010 May 19; Authors: Chen FM, Zhang M, Wu ZF Inspired by physiological events that accompany the "wound healing cascade", the concept of developing a tissue either in vitro or in vivo has led to the integration of a wide variety of growth factors (GFs) in tissue engineering strategies in an effort to mimic the natural microenvironments of tissue formation and repair. Localised delivery of exogenous GFs is believed to be therapeutically effective for replication of cellular components involved in tissue development and the healing process, thus making them important factors for tissue regeneration. However, any treatment aiming to mimic the critical aspects of the natural biological process should not be limited to the provision of a single GF, but rather should release multiple therapeutic agents at an optimised ratio, each at a physiological dose, in a specific spatiotemporal pattern. Despite several obstacles, delivery of more than one GF at rates mimicking an in vivo situation has promising potential for ! the clinical management of severely diseased tissues. This article summarises the concept of and early approaches toward the delivery of dual or multiple GFs, as well as current efforts to develop sophisticated delivery platforms for this ambitious purpose, with an emphasis on the application of biomaterials-based deployment technologies that allow for controlled spatial presentation and release kinetics of key biological cues. Additionally, the use of platelet-rich plasma or gene therapy is addressed as alternative, easy, cost-effective and controllable strategies for the release of high concentrations of multiple endogenous GFs, followed by an update of the current progress and future directions of research utilising release technologies in tissue engineering and regenerative medicine. PMID: 20493521 [PubMed - as supplied by publisher] | | |
| Purified Hematopoietic Stem Cell Transplantation: The Next Generation of Blood and Immune Replacement.
May 25, 2010 at 6:32 AM
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| | Purified Hematopoietic Stem Cell Transplantation: The Next Generation of Blood and Immune Replacement. Immunol Allergy Clin North Am. 2010 May;30(2):159-171 Authors: Czechowicz A, Weissman IL Replacement of disease-causing stem cells with healthy ones has been achieved clinically via hematopoietic cell transplantation (HCT) for the last 40 years, as a treatment modality for a variety of cancers and immunodeficiencies with moderate, but increasing, success. This procedure has traditionally included transplantation of mixed hematopoietic populations that include hematopoietic stem cells (HSC) and other cells, such as T cells. This article explores and delineates the potential expansion of this technique to treat a variety of inherited diseases of immune function, the current barriers in HCT and pure HSC transplantation, and the up-and-coming strategies to combat these obstacles. PMID: 20493393 [PubMed - as supplied by publisher] | | |
| The effect of clinical experience on dentine bonding effectiveness: students versus trained dentists.
May 25, 2010 at 6:32 AM
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| | The effect of clinical experience on dentine bonding effectiveness: students versus trained dentists. J Oral Rehabil. 2010 May 21; Authors: Ueda M, Mine A, DE Munck J, Hakogi T, VAN Meerbeek B, Kuboki T Summary Clinical successful application of dentine adhesives depends not only on material-related but also on operator-related factors. The purpose of this study was to evaluate the dentine bonding effectiveness of a self-etch composite cement applied by operators with or without clinical experience under well-standardized, randomized and blind conditions. Forty-eight bovine dentine surfaces were randomly divided into two groups. The first group consisted of eight dental students with no clinical experience at all, and the second group consisted of eight dentists with extensive experience in adhesive dentistry (mean experience of 11.4 years). Next, a 4-mm-diameter stainless steel rod (SUS-304) was bonded to the dentine surface using Panavia Fluoro cement (Kuraray Medical Inc., Tokyo, Japan). After application procedures, the specimens were randomized and shear bond-strength measurements were performed by a single blinded operator. Mann-Whitney U test was used to d! etermine statistical differences in bond strength between the two groups, and Kruskal-Wallis was used to determine statistical difference between the student and dentist groups. The means and standard deviations of bond strength were 11.5 +/- 8.1 MPa for the student group and 7.1 +/- 4.3 MPa for the dentist group, respectively. The bond strength of the student group was significantly higher than that of the dentist group. However, the variability in bond strength was significantly higher in the student group, and some specimens failed prior to actual testing (included as 0 MPa). Clinical experience did not have a positive effect on the bonding effectiveness of the self-etch composite cement to dentine. PMID: 20492442 [PubMed - as supplied by publisher] | | |
| Mesenchymal Stem Cells Overexpressing Ephrin-B2 Rapidly Adopt an Early Endothelial Phenotype with Simultaneous Reduction of Osteogenic Potential.
May 25, 2010 at 6:32 AM
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| | Mesenchymal Stem Cells Overexpressing Ephrin-B2 Rapidly Adopt an Early Endothelial Phenotype with Simultaneous Reduction of Osteogenic Potential. Tissue Eng Part A. 2010 May 22; Authors: Duffy GP, D'Arcy S, Ahsan T, Nerem RM, O'Brien T, Barry F Restoration of the vascular supply to ischemic tissues is of high clinical relevance, and proangiogenic therapies aim to reduce morbidity and mortality rates associated with the onset of cardiovascular disease. Stem cell therapy has been proposed as a potentially useful proangiogenic therapy. Mesenchymal stem cells (MSCs) have been shown to be proangiogenic and produce a number of cytokines involved in vessel development and maturation. Preclinical studies have reported increased angiogenesis after MSC delivery to the heart, and similar outcomes have been reported in recent clinical trials. Stem-cell-mediated neovascularization has been augmented by genetic modification with overexpression of angiogenic cytokines, including vascular endothelial growth factor (VEGF) and platelet-derived growth factor, showing promising results. In this study we aimed to enhance the proangiogenic capability of MSCs. MSCs were genetically modified to overexpress a versatile molecule,! Ephrin-B2, involved in tissue morphogenesis and vascular development to enhance inherent neovascularization potential. Using nucleofection, Ephrin-B2 was transiently overexpressed on the cell surface of MSCs to recapitulate embryonic signaling and promote neovascularization. Ephrin-B2-expressing MSCs adopted an early endothelial phenotype under endothelial cell culture conditions increasing expression of von Willebrand factor and VEGF-Receptor 2. The cells had an increased ability to form vessel-like structures, produce VEGF, and incorporate into newly formed endothelial cell structures. These data indicate that MSCs expressing Ephrin-B2 represent a novel proangiogenic cell source to promote neovascularization in ischemic tissues. PMID: 20491587 [PubMed - as supplied by publisher] | | |
| Intact fetal ovarian cord formation promotes mouse oocyte survival and development.
May 25, 2010 at 6:32 AM
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| | Intact fetal ovarian cord formation promotes mouse oocyte survival and development. BMC Dev Biol. 2010;10:2 Authors: Nicholas CR, Haston KM, Pera RA BACKGROUND: Female reproductive potential, or the ability to propagate life, is limited in mammals with the majority of oocytes lost before birth. In mice, surviving perinatal oocytes are enclosed in ovarian follicles for subsequent oocyte development and function in the adult. Before birth, fetal germ cells of both sexes develop in clusters, or germline cysts, in the undifferentiated gonad. Upon sex determination of the fetal gonad, germ cell cysts become organized into testicular or ovarian cord-like structures and begin to interact with gonadal somatic cells. Although germline cysts and testicular cords are required for spermatogenesis, the role of cyst and ovarian cord formation in mammalian oocyte development and female fertility has not been determined. RESULTS: Here, we examine whether intact fetal ovarian germ and somatic cell cord structures are required for oocyte development using mouse gonad re-aggregation and transplantation to disrupt gonadal organiz! ation. We observed that germ cells from disrupted female gonad prior to embryonic day e13.5 completed prophase I of meiosis but did not survive following transplantation. Furthermore, re-aggregated ovaries from e13.5 to e15.5 developed with a reduced number of oocytes. Oocyte loss occurred before follicle formation and was associated with an absence of ovarian cord structure and ovary disorganization. However, disrupted ovaries from e16.5 or later were resistant to the re-aggregation impairment and supported robust oocyte survival and development in follicles. CONCLUSIONS: Thus, we demonstrate a critical window of oocyte development from e13.5 to e16.5 in the intact fetal mouse ovary, corresponding to the establishment of ovarian cord structure, which promotes oocyte interaction with neighboring ovarian somatic granulosa cells before birth and imparts oocytes with competence to survive and develop in follicles. Because germline cyst and ovarian cord structures are conserved! in the human fetal ovary, the identification of genetic compo! nents an d molecular mechanisms of pre-follicle stage germ and somatic cell structures may be important for understanding human female infertility. In addition, this work provides a foundation for development of a robust fetal ovarian niche and transplantation based system to direct stem cell-derived oocyte differentiation as a potential therapeutic strategy for the treatment of infertility. PMID: 20064216 [PubMed - indexed for MEDLINE] | | |
| Hypoxia increases Sca-1/CD44 co-expression in murine mesenchymal stem cells and enhances their adipogenic differentiation potential.
May 25, 2010 at 6:28 AM
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| | Hypoxia increases Sca-1/CD44 co-expression in murine mesenchymal stem cells and enhances their adipogenic differentiation potential. Cell Tissue Res. 2010 May 23; Authors: Valorani MG, Germani A, Otto WR, Harper L, Biddle A, Khoo CP, Lin WR, Hawa MI, Tropel P, Patrizi MP, Pozzilli P, Alison MR Mesenchymal stem cells (MSCs) are usually cultured under normoxic conditions (21% oxygen). However, in vivo, the physiological "niches" for MSCs have a much lower oxygen tension. Because of their plasticity, stem cells are particularly sensitive to their environments, and oxygen tension is one developmentally important stimulus in stem cell biology and plays a role in the intricate balance between cellular proliferation and commitment towards differentiation. Therefore, we investigated here the effect of hypoxia (2% oxygen) on murine adipose tissue (AT) MSC proliferation and adipogenic differentiation. AT cells were obtained from the omental fat and AT-MSCs were selected for their ability to attach to the plastic dishes, and were grown under normoxic and hypoxic conditions. Prior exposure of MSCs to hypoxia led to a significant reduction of ex vivo expansion time, with significantly increased numbers of Sca-1(+) as well as Sca-1(+)/CD44(+)double-positive cells. Un! der low oxygen culture conditions, the AT-MSC number markedly increased and their adipogenic differentiation potential was reduced. Notably, the hypoxia-mediated inhibition of adipogenic differentiation was reversible: AT-MSCs pre-exposed to hypoxia when switched to normoxic conditions exhibited significantly higher adipogenic differentiation capacity compared to their pre-exposed normoxic-cultured counterparts. Accordingly, the expression of adipocyte-specific genes, peroxisome proliferator activated receptor gamma (Ppargamma), lipoprotein lipase (Lpl) and fatty acid binding protein 4 (Fabp4) were significantly enhanced in hypoxia pre-exposed AT-MSCs. In conclusion, pre-culturing MSCs under hypoxic culture conditions may represent a strategy to enhance MSC production, enrichment and adipogenic differentiation. PMID: 20496083 [PubMed - as supplied by publisher] | | |
| A tissue adhesives evaluated in vitro and in vivo analysis.
May 25, 2010 at 6:06 AM
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| | A tissue adhesives evaluated in vitro and in vivo analysis. J Biomed Mater Res A. 2010 Jul;94(1):326-32 Authors: Mo X, Iwata H, Ikada Y In this study, three kinds of two-component adhesive glues were prepared, namely, gel-dext glue made from modified gelatin and dextran, gel-HES glue made from modified gelatin and hydroxyethyl starch (HES), and chit-dext glue made from chitosan and modified dextran. Upon mixing the two-component solution together crosslinking occurred and a gel formed in several seconds, which would seal the wound tissue and stop the bleeding. The adhesive ability of those three prepared glues was evaluated in vitro and in vivo separately by measuring the bonding strength to two piece of porcine skin and the adhesive strength after sealing the skin incisions on the back of rat. Fibrin glue was used as comparing. Gel-dext glue and gel-HES glue shown higher bonding strength and adhesive strength than chit-dext glue and fibrin glue. Histology test of incision tissues given by both HE and MTC methods, the former shown that gel-dext and gel-HES glues, like fibrin glue, have only normal! initial inflammation to skin tissue, which almost disappear from 9 days but chit-dext glue seams have heaver inflammation, which may last to 12 days; the later shown gel-dext and gel-HES glues similar to fibrin glue, can heal the wound fast than that of chit-dext glue. The hemostatic ability for gel-HES glue was also tested on a cut liver of rat, which depend on the gel formation speed when the two-composite solutions were mixed together. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010. PMID: 20496438 [PubMed - in process] | | |
| Muscle-derived stem cells: isolation, characterization, differentiation, and application in cell and gene therapy.
May 25, 2010 at 6:06 AM
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| | Muscle-derived stem cells: isolation, characterization, differentiation, and application in cell and gene therapy. Cell Tissue Res. 2010 May 22; Authors: Wu X, Wang S, Chen B, An X Muscle tissue represents an abundant, accessible, and replenishable source of adult stem cells for cell-based tissue and genetic engineering. A population of cells isolated from muscle exhibits both multipotentiality and self-renewal capabilities. Satellite cells, referred to by many investigators as muscle stem cells, are myogenic precursors that are capable of regenerating muscle and that demonstrate self-renewal properties; however, they are considered to be committed to the myogenic lineage. Muscle-derived stem cells (MDSCs), which may represent a predecessor of the satellite cell, are considered to possess a higher regeneration capacity and to exhibit better cell survival and a broader range of multilineage capabilities. Remarkably, MDSCs are not only able to differentiate into mesodermal cell types including the myogenic, adipogenic, osteogenic, chondrogenic, endothelial, and hematopoietic lineages, but also possess the potential to break germ layer commitme! nt and differentiate into ectodermal lineages including neuron-like cells under certain conditions. This article reviews the current preclinical studies and potential clinical applications of MDSC-mediated gene therapy and tissue-engineering and methods for MDSC isolation, differentiation, and molecular characterization. PMID: 20495827 [PubMed - as supplied by publisher] | | |
| Stem cell-based dental tissue engineering.
May 25, 2010 at 6:06 AM
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| | Stem cell-based dental tissue engineering. ScientificWorldJournal. 2010;10:901-16 Authors: Zivkovic P, Petrovic V, Najman S, Stefanovic V The development of biological and biomaterial sciences profiled tissue engineering as a new and powerful tool for biological replacement of organs. The combination of stem cells and suitable scaffolds is widely used in experiments today, in order to achieve partial or whole organ regeneration. This review focuses on the use of tissue engineering strategies in tooth regeneration, using stem cells and stem cells/scaffold constructs. Although whole tooth regeneration is still not possible, there are promising results. However, to achieve this goal, it is important to understand and further explore the mechanisms underlying tooth development. Only then will we be able to mimic the natural processes with the use of stem cells and tissue engineering techniques. PMID: 20495769 [PubMed - in process] | | |
| Noninvasive transplantation of bone marrow stromal cells for ischemic stroke: preliminary study with a thermoreversible gelation polymer hydrogel.
May 25, 2010 at 6:06 AM
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| | Noninvasive transplantation of bone marrow stromal cells for ischemic stroke: preliminary study with a thermoreversible gelation polymer hydrogel. Neurosurgery. 2010 Jun;66(6):1140-7 Authors: Osanai T, Kuroda S, Yasuda H, Chiba Y, Maruichi K, Hokari M, Sugiyama T, Shichinohe H, Iwasaki Y OBJECTIVE: Recent studies have indicated that bone marrow stromal cells (BMSCs) have the potential to improve neurological function when transplanted into animal models of cerebral infarct. However, it is still undetermined how the BMSCs should be transplanted to obtain the most efficient therapeutic benefits safely. The aim of this study was to assess whether a thermoreversible gelation polymer (TGP) hydrogel acts as a noninvasive, valuable scaffold in BMSC transplantation for infarct brain. METHODS: The mice were subjected to permanent middle cerebral artery occlusion. Vehicle, BMSC suspension, or the BMSC-TGP construct was transplanted onto the ipsilateral intact neocortex at 7 days after the insult. Neurological symptoms were assessed throughout the experiments. The fate of the transplanted BMSC was examined 8 weeks after transplantation with immunohistochemistry. RESULTS: TGP hydrogel completely disappeared and provoked no inflammation in the host brain. Many! transplanted cells were widely engrafted in the ipsilateral cerebrum, including the dorsal neocortex adjacent to the cerebral infarct in the BMSC-TGP construct-treated mice. Their number was significantly larger than in the BMSC-treated mice. The majority were positive for both NeuN and MAP2 and morphologically simulated the neurons. CONCLUSION: The findings suggest that surgical transplantation of tissue-engineered BMSCs onto the intact neocortex enhances the engraftment of donor cells around the cerebral infarct. These data may be useful in developing a noninvasive but efficient paradigm in neural tissue engineering. TGP hydrogel can be a promising candidate for valuable scaffolds in BMSC transplantation for central nervous system disorders because of its unique biochemical properties. PMID: 20495428 [PubMed - in process] | | |
| Protein Expression Profiles during Osteogenic Differentiation of Mesenchymal Stem Cells Derived from Human Umbilical Cord Blood.
May 25, 2010 at 6:06 AM
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| | Protein Expression Profiles during Osteogenic Differentiation of Mesenchymal Stem Cells Derived from Human Umbilical Cord Blood. Tohoku J Exp Med. 2010;221(2):141-50 Authors: Kim S, Min WK, Chun S, Lee W, Chung HJ, Choi SJ, Yang SE, Yang YS, Yoo JI Mesenchymal stem cells (MSCs) can potentially differentiate along multiple lineages and be expanded in vitro, making them highly attractive candidates for cell therapy and tissue engineering applications. This study sought to investigate the critical proteins involved in osteogenic differentiation of mesenchymal stem cells derived from umbilical cord blood (UCB-MSCs). MSCs, which were isolated from three different preparations of human UCB, were osteoinduced, and total proteins were extracted from the cells. Two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) was performed on the day (d) of induction d0, and on d2, d7, and d21 of differentiation. The optical density (OD) of each spot was measured, and spots with a mean OD of three cell lines of MSCs that increased > 30 or decreased < 0.1 relative to a previous time point were selected. Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF/MS) was used to identify t! he proteins. Through database searches, the properties and functions of the proteins were investigated and then classified according to the Gene Ontology classification. Among the 308 spots observed in the 2-D gel, 16 proteins with a mean OD ratio > 30, and 20 proteins with a mean OD ratio < 0.1 were identified during the differentiation process. Additionally, the distribution of differentially expressed proteins according to cellular component and molecular function criteria differed depending on whether protein expression increased or decreased during differentiation. The results of this study will comprise an initial proteomic database for UCB-MSCs differentiation. PMID: 20495303 [PubMed - in process] | | |
| The Importance of Elastin to Aortic Development in Mice.
May 25, 2010 at 6:06 AM
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| | The Importance of Elastin to Aortic Development in Mice. Am J Physiol Heart Circ Physiol. 2010 May 21; Authors: Wagenseil JE, Ciliberto CH, Knutsen RH, Levy MA, Kovacs A, Mecham RP Elastin is an essential component of vertebrate arteries that provides elasticity and stores energy during the cardiac cycle. Elastin production in the arterial wall begins mid-gestation but increases rapidly during the last third of human and mouse development, just as blood pressure and cardiac output increase sharply. The aim of this study is to characterize the structure, hemodynamics and mechanics of developing arteries with reduced elastin levels and determine the critical time period where elastin is required in the vertebrate cardiovascular system. Mice that lack elastin (Eln-/-) or have approximately one-half the normal level (Eln+/-) show relatively normal cardiovascular development up to embryonic day 18 as assessed by arterial morphology, left ventricular blood pressure, and cardiac function. Previous work showed that just a few days later, at birth, Eln-/- mice die with high blood pressure and tortuous, stenotic arteries. During this period from E18 t! o birth, Eln+/- mice add extra layers of smooth muscle cells to the vessel wall and have a mean blood pressure 25% higher than wildtype animals. These findings demonstrate that elastin is only necessary for normal cardiovascular structure and function in mice starting in the last few days of fetal development. The large increases in blood pressure during this period may push hemodynamic forces over a critical threshold where elastin becomes required for cardiovascular function. Understanding the interplay between elastin amounts and hemodynamic forces in developing vessels will help design treatments for human elastinopathies and optimize protocols for tissue engineering. PMID: 20495146 [PubMed - as supplied by publisher] | | |
| Engineering the Crystalline Lens with a Biodegradable or Non-Degradable Scaffold.
May 25, 2010 at 6:06 AM
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| | Engineering the Crystalline Lens with a Biodegradable or Non-Degradable Scaffold. Exp Eye Res. 2010 May 19; Authors: Gwon A, Gruber L Both a biodegradable hyaluronic acid (HA) and a nondegradable polymeric gel were evaluated as scaffolds for tissue engineering the lens in Dutch Belt pigmented and New Zealand white rabbits. Following removal of the crystalline lens through a 2 mm capsulorhexis, a collagen patch or a silicone plug was placed in the capsule bag to seal the capsulotomy. In Part I, a cross-linked HA or cohesive solution of HA was injected into the capsule bag. In Part II, a synthetic polymer (SP) was injected into the capsular bag of one eye and HA followed by SP (HA/SP) was injected into the capsule bag of the opposite eye. At 3 months focal Nd:YAG laser photocoagulation was performed in an attempt to remove some retained HA gel in one eye. Overall the regenerated lenses of the HA gel groups were spherical with excellent cortical structure and clarity and a spherical nucleus of condensed HA gel. In the one eye treated with focal photocoagulation, partial clearing of the retained HA ! gel was noted. In the SP and HA/SP eyes, lens regrowth around the polymer was generally clear in the anterior and peripheral capsule bag and more opacified posterior to the polymeric scaffold. In summary, naturally regenerating lens tissue was directed to grow in a more normal, regular pattern by providing a biodegradable hyaluronic acid scaffold or a nondegradable polymeric optical scaffold. PMID: 20493837 [PubMed - as supplied by publisher] | | |
| Toward delivery of multiple growth factors in tissue engineering.
May 25, 2010 at 6:06 AM
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| | Toward delivery of multiple growth factors in tissue engineering. Biomaterials. 2010 May 19; Authors: Chen FM, Zhang M, Wu ZF Inspired by physiological events that accompany the "wound healing cascade", the concept of developing a tissue either in vitro or in vivo has led to the integration of a wide variety of growth factors (GFs) in tissue engineering strategies in an effort to mimic the natural microenvironments of tissue formation and repair. Localised delivery of exogenous GFs is believed to be therapeutically effective for replication of cellular components involved in tissue development and the healing process, thus making them important factors for tissue regeneration. However, any treatment aiming to mimic the critical aspects of the natural biological process should not be limited to the provision of a single GF, but rather should release multiple therapeutic agents at an optimised ratio, each at a physiological dose, in a specific spatiotemporal pattern. Despite several obstacles, delivery of more than one GF at rates mimicking an in vivo situation has promising potential for ! the clinical management of severely diseased tissues. This article summarises the concept of and early approaches toward the delivery of dual or multiple GFs, as well as current efforts to develop sophisticated delivery platforms for this ambitious purpose, with an emphasis on the application of biomaterials-based deployment technologies that allow for controlled spatial presentation and release kinetics of key biological cues. Additionally, the use of platelet-rich plasma or gene therapy is addressed as alternative, easy, cost-effective and controllable strategies for the release of high concentrations of multiple endogenous GFs, followed by an update of the current progress and future directions of research utilising release technologies in tissue engineering and regenerative medicine. PMID: 20493521 [PubMed - as supplied by publisher] | | |
| IOM Proposal Not So Good, Says One CIRM Director
May 25, 2010 at 1:31 AM
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| One director of the California stem cell agency is less than enamored of a proposal for a study of the agency by the prestigious Institute of Medicine.
Jonathan Shestack, co-founder of Cure Autism Now and a Hollywood producer, said in an email,
"We may have complaints about CIRM, but they are not of the sort we expect IOM, its cultural and ideological doppelganger, to point out.
"Unless there | | |
| State's Top Fiscal Officer Lauds Disclosure Proposal Likely to Affect CIRM
May 25, 2010 at 1:07 AM
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| State Controller John Chiang, chairman of a key panel overseeing the California stem cell agency, today praised proposed NIH financial disclosure rules that are almost certain to have an impact on CIRM, one that the agency has avoided so far.
Chiang, the state's top fiscal officer, is head of the Citizens Financial Accountability Oversight Committee(CFAOC), a sister group to CIRM and one that | | | | 
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