|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | High-Efficiency Induction of Neural Conversion in hESCs and hiPSCs with a Single Chemical Inhibitor of TGF-beta Superfamily Receptors. Stem Cells. 2010 Aug 23; Authors: Zhou J, Su P, Li D, Tsang S, Duan E, Wang F Chemical compounds have emerged as powerful tools for modulating embryonic stem cell (ESC) functions and deriving induced pluripotent stem cells (iPSCs), but documentation of compound-induced efficient directed differentiation in human ESC (hESCs) and human iPSC (hiPSCs) is limited. By screening a collection of chemical compounds, we identified compound C (also denoted as dorsomorphin), a protein kinase inhibitor, as a potent regulator of hESC and hiPSC fate decisions. Compound C suppresses mesoderm, endoderm and trophoectoderm differentiation and induces rapid and high-efficiency neural conversion in both hESCs and hiPSCs (88.7% and 70.4%, respectively). Interestingly, compound C is ineffective in inducing neural conversion in mouse ESCs (mESCs). Large-scale kinase assay revealed that compound C targets at least seven TGF-beta superfamily receptors, including both type I and type II receptors, and thereby blocks both the Activin and BMP signaling pathways in hESCs. Dual inhibition of Activin and BMP signaling accounts for the effects of compound C on hESC differentiation and neural conversion. We also identified muscle segment homeobox gene 2 (MSX2) as a downstream target gene of compound C and a key signaling intermediate of the BMP pathway in hESCs. Our findings provide a single-step cost-effective method for efficient derivation of neural progenitor cells in adherent culture from human pluripotent stem cells. Therefore, it will be uniquely suitable for the production of neural progenitor cells in large scale and should facilitate the use of stem cells in drug screening and regenerative medicine and study of early human neural development. PMID: 20734356 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Immunomodulatory Properties of Mesenchymal Stem Cells Derived from Dental Pulp and Dental Follicle are Susceptible to Activation by Toll-Like Receptor Agonists. Stem Cells Dev. 2010 Aug 23; Authors: Tomic S, Djokic J, Vasilijic S, Vucevic D, Todorovic V, Supic G, Colic M Adult mesenchymal stem cells (MSCs) have recently become a potent tool in regenerative medicine. Due to certain shortcomings of obtaining bone marrow MSCs, alternate sources of MSCs have been sought. In this work we studied MSCs from dental pulp (DP-MSCs) and dental follicle (DF-MSCs), isolated from the same tooth/donor, in order to define differences in their phenotypic properties, differentiation potential and immunomodulatory activities. Both cell types showed colony forming ability and expressed typical MSCs markers, but differed in the levels of their expression. DF-MSCs proliferated faster, contained cells larger in diameter, exhibited a higher potential to form adipocytes and a lower potential to form chondrocytes and osteoblasts, compared to DP-MSCs. In contrast to DF-MSCs, DP-MSCs produced the transforming growth factor (TGF)-beta and suppressed proliferation of peripheral blood mononuclear cells, which could be neutralized with anti-TGF-beta antibody. The treatment with TLR3 agonist augmented the suppressive potential of both cell types and potentiated TGF-beta and interleukin (IL)-6 secretions by these cells. TLR4 agonist augmented the suppressive potential of DF-MSCs and increased TGF-beta production, but abrogated the immunosuppressive activity of DP-MSCs by inhibiting TGF-beta production and the expression of indolamine-2,3-dioxygenase-1. Some of these effects correlated with the higher expression of TLR3 and TLR4 by DP-MSCs compared to DF-MSCs. When transplanted in imunocompetent xenogenic host, both cell types induced formation of granulomatous tissue. In conclusion, our results suggest that dental MSCs are functionally different and each of these functions should be further explored in vivo prior to their specific biomedical applications. PMID: 20731536 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Stromal hyaluronan interaction with epithelial CD44 variants promotes prostate cancer invasiveness by augmenting expression and function of hepatocyte growth factor and androgen receptor. J Biol Chem. 2010 Jun 25;285(26):19821-32 Authors: Ghatak S, Hascall VC, Markwald RR, Misra S The main aim of our study is to determine the significance of the stromal microenvironment in the malignant behavior of prostate cancer. The stroma-derived growth factors/cytokines and hyaluronan act in autocrine/paracrine ways with their receptors, including receptor-tyrosine kinases and CD44 variants (CD44v), to potentiate and support tumor epithelial cell survival. Overexpression of hyaluronan, CD44v9 variants, and stroma-derived growth factors/cytokines are specific features in many cancers, including prostate cancer. Androgen/androgen receptor interaction has a critical role in regulating prostate cancer growth. Our previous study showed that 1) that increased synthesis of hyaluronan in normal epithelial cells promotes expression of CD44 variants; 2) hyaluronan interaction with CD44v6-v9 promotes activation of receptor-tyrosine kinase, which stimulates phosphatidylinositol 3-kinase-induced cell survival pathways; and 3) CD44v6/short hairpin RNA reduces colon tumor growth in vivo (Misra, S., Hascall, V. C., De Giovanni, C., Markwald, R. R., and Ghatak, S. (2009) J. Biol. Chem. 284, 12432-12446). Our results now show that hepatocyte growth factor synthesized by myofibroblasts associated with prostate cancer cells induces activation of HGF-receptor/cMet and stimulates hyaluronan/CD44v9 signaling. This, in turn, stabilizes the androgen receptor functions in prostate cancer cells. The stroma-derived HGF induces a lipid raft-associated signaling complex that contains CD44v9, cMet/phosphatidylinositol 3-kinase, HSP90 and androgen receptor. CD44v9/short hairpin RNA reverses the assembly of these components in the complex and inhibits androgen receptor function. Our results provide new insight into the hyaluronan/CD44v9-regulated androgen receptor function and the consequent malignant activities in prostate cancer cells. The present study describes a physiologically relevant in vitro model for studying the molecular mechanisms by which stroma-derived HGF and hyaluronan influence androgen receptor and CD44 functions in the secretory epithelia during prostate carcinogenesis. PMID: 20200161 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Canine adipose-derived-mesenchymal stem cells do not lose stem features after a long-term cryopreservation. Res Vet Sci. 2010 Aug 21; Authors: Martinello T, Bronzini I, Maccatrozzo L, Mollo A, Sampaolesi M, Mascarello F, Decaminada M, Patruno M Adult stem cells are nowadays used for treating several pathologies. A putative stem cell population was found in the adipose tissue of mammals and canine adipose tissue-derived-mesenchymal stem cells (cA-MSC) have been shown to possess the capacity to differentiate into several lineages. The main goal of our research was to fully characterize cA-MSC and examine the effects of cryopreservation on their stemness features. Each sample of cA-MSC was analyzed immediately and then again after being frozen in liquid nitrogen for one year. After the cryopreservation period cells conserved their fibroblast-like morphology, alkaline phosphatase positivity and CD expression but showed a lower proliferation ratio and a lower telomerase activity in comparison with fresh cells. Finally, the cryopreservation protocol did not change the cA-MSC adipogenic, osteogenic and myogenic differentiative potential. Our data demonstrate that stored cA-MSC might represent a promising type of progenitor cell for autologous cellular-based therapies in veterinary medicine. PMID: 20732703 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Stem cells in the treatment of inflammatory arthritis. Best Pract Res Clin Rheumatol. 2010 Aug;24(4):565-574 Authors: Tyndall A, van Laar JM Autologous haematopoietic stem cell transplantation in patients with rheumatoid arthritis (RA) resulted in a positive short-term outcome clinically with low treatment-related toxicity. However, early conditioning regimens were of low immunoablative intensity and most patients relapsed. Mechanistic studies suggest that residual lesional effector cells may have been responsible for the relapses. The introduction of biopharmaceuticals has, for the moment, reduced the need for further experimental studies. Juvenile idiopathic arthritis patients, mostly of the systemic subgroup, have shown nearly 33% durable drug-free remission, but with significant toxicity, including fatal macrophage-activation syndrome early in the programme. Later modifications to the protocol have reduced this toxicity. Mesenchymal stem cells (MSCs), derived from several sources including bone marrow and adipose tissue, are being tested as tissue-regenerative and immunomodulating agents in many autoimmune diseases and animal models of inflammatory arthritis have been positive. MSCs and other stromal cells derived from actively inflamed synovium and peripheral blood of RA patients do not always demonstrate a full range of differentiation potential compared with healthy MSCs, although their immunomodulalatory capacity is unimpaired. PMID: 20732653 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Dynamics of Bone Marrow-Derived Endothelial Progenitor Cell/Mesenchymal Stem Cell Interaction in Co-culture and its Implications in Angiogenesis. Biochem Biophys Res Commun. 2010 Aug 20; Authors: Aguirre A, Planell JA, Engel E Tissue engineering aims to regenerate tissues and organs by using cell and biomaterial-based approaches. One of the current challenges in the field is to promote proper vascularization in the implant to prevent cell death and promote host integration. Bone marrow endothelial progenitor cells (BM-EPCs) and mesenchymal stem cells (MSCs) are bone marrow resident stem cells widely employed for proangiogenic applications. In vivo, they are likely to interact frequently both in the bone marrow and at sites of injury. In this study, the physical and biochemical interactions between BM-EPCs and MSCs in an in vitro co-culture system were investigated to further clarify their roles in vascularization. BM-EPC/MSC co-cultures established close cell-cell contacts soon after seeding and self-assembled to form elongated structures at 3 days. Besides direct contact, cells also exhibited vesicle transport phenomena. When co-cultured in Matrigel, tube formation was greatly enhanced even in serum-starved, growth factor free medium. Both MSCs and BM-EPCs contributed to these tubes. However, cell proliferation was greatly reduced in co-culture and morphological differences were observed. Gene expression and cluster analysis for wide panel of angiogenesis-related transcripts demonstrated up-regulation of angiogenic markers but down-regulation of many other cytokines. These data suggest that cross-talk occurs in between BM-EPCs and MSCs through paracrine and direct cell contact mechanisms leading to modulation of the angiogenic response. PMID: 20732306 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | [Progressing study in osteoblasts cultured in vitro] Zhongguo Gu Shang. 2010 Jul;23(7):562-5 Authors: Xu YJ, Zhao JN With the development of cell culture technology in vitro, people have successfully cultivated osteoblast cells of typical characteristics from a number of animal skull, bone marrow, periosteum and bone tissues; studies have shown that these osteoblasts have good biological characteristics, can create bone tissue in different environments, can apply joint stand for the construction of tissue engineered bone, be implanted in the body to repair bone defects. In this article, the source of osteoblast, regulatory factor, composite graft and Chinese medicine research progress were reviewed. PMID: 20701143 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Minced urothelium to create epithelialized subcutaneous conduits. J Urol. 2010 Aug;184(2):757-61 Authors: Fossum M, Zuhaili B, Bergmann J, Spielmann M, Hirsch T, Eriksson E PURPOSE: We used in vivo cell expansion to create 3-dimensional subcutaneous conduits lined with an inner layer of autologous urothelial mucosa. MATERIALS AND METHODS: Laparotomy and excision of a fifth of the bladder were done in 5 female Yorkshire pigs (Parsons Farm, Westhampton, Massachusetts) under general anesthesia. After mechanical removal of the detrusor muscle the bladder mucosa was minced to obtain 0.2 x 0.8 x 0.8 mm particles, which were attached to the outer surface of latex tubes using a thin layer of fibrin glue. Seven to 10 tubes were placed in the abdominal wall subcutaneous tissue in each original donor pig with tubes lacking particles serving as controls. Biopsy was done 1 to 4 weeks after transplantation for histological evaluation. RESULTS: One week after transplantation particles were still present in the granulation tissue. At 2 weeks the epithelium was differentiated with transitional uroepithelium facing the lumen, ie toward the tube. No epithelium was detected around control tubes. CONCLUSIONS: After autologous transplantation of bladder mucosal particles organized in 3-dimensional fashion in pig subcutaneous tissue the transplanted cells proliferated, migrated and reorganized to form a continuous epithelial lining facing the lumen. This novel approach to urothelial transplantation may allow successful formation of a conduit to the bladder or of a neourethra. PMID: 20639052 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Human satellite progenitor cells for use in myofascial repair: isolation and characterization. Ann Plast Surg. 2010 Jun;64(6):794-9 Authors: Logan MS, Propst JT, Nottingham JM, Goodwin RL, Pabon DF, Terracio L, Yost MJ, Fann SA Current use of prosthetic meshes and implants for myofascial reconstruction has been associated with infectious complications, long-term failure, and dissatisfying cosmetic results. Our laboratory has developed a small animal model for ventral hernia repair, which uses progenitor cells isolated from a skeletal muscle biopsy. In the model, progenitor cells are expanded in vitro, seeded onto a nonimmunogenic, novel aligned scaffold of bovine collagen and placed into the defect as a living adjuvant to the innate repair mechanism. The purpose of the current investigation is to examine the feasibility of translating our current model to humans. As a necessary first step we present our study on the efficacy of isolating satellite cells from 9 human donor biopsies. We were able to successfully translate our progenitor cell isolation and culture protocols to a human model with some modifications. Specifically, we have isolated human satellite muscle cells, expanded them in culture, and manipulated these cells to differentiate into myotubes in vitro. Immunohistochemical analysis allowed the characterization of distinct progenitor cell cycle stages and quantification of approximate cell number. Furthermore, isolated cells were tracked via cytoplasmic nanocrystal labeling and observed using confocal microscopy. PMID: 20407365 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | The effect of "minimally invasive transfer of angiosomes" on vascularization of prefabricated/prelaminated tissues. Ann Plast Surg. 2010 Apr;64(4):491-5 Authors: Demirtas Y, Engin MS, Aslan O, Ayas B, Karacalar A Prefabrication and prelamination are experimental and clinical applications of reconstructive surgery and inspired the vascularization challenge of engineered tissues. The purpose of this study is to test the efficiency of "minimally invasive transfer of angiosomes" to enhance the vascularization of the final construct during prefabrication and prelamination. Fifteen rabbits were used for this study. Three of the animals were used in a pilot study to develop the protocol. During the study, thoracodorsal and lateral thoracic vascular pedicles on each side constituted 4 study groups. The pedicles were prepared to simulate prelamination with and without transfer of angiosomes, and prefabrication with and without transfer of angiosomes. In all of the groups, a 10 x 15 mm auricular cartilage graft was used as the construct to be vascularized. After 2 weeks, vascularization of the grafts was evaluated by means of microangiography and histology. Results indicate that both prelamination and prefabrication with transfer of angiosomes displayed better vascularization, both qualitatively and quantitatively. However, prelamination with transfer of angiosomes group displayed distinct statistical superiority. The results suggest that minimally invasive transfer of angiosomes coupled with the procedure significantly increases the induction of angiogenesis during prelamination and prefabrication. PMID: 20224348 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | On Sunday, we carried an item dealing with the political environment in California surrounding a possible additional $4 billion bond measure to continue financing the California stem cell agency.
CIRM Director Jeff Sheehy, chairman of the board's Scientific Subcommittee, longtime patient advocate and communications manager at UC San Francisco, sent along the following response. It was received | | | | | | | | | | | | | | | | | | | | | | | | | Ageing and neurodegenerative diseases. Ageing Res Rev. 2010 Aug 20; Authors: Hung CW, Chen YC, Hsieh WL, Chiou SH, Kao CL Ageing, which all creatures must encounter, is a challenge to every living organism. In the human body, it is estimated that cell division and metabolism occurs exuberantly until about 25 years of age. Beyond this age, subsidiary products of metabolism and cell damage accumulate, and the phenotypes of ageing appear, causing disease formation. Among these age-related diseases, neurodegenerative diseases have drawn a lot of attention due to their irreversibility, lack of effective treatment, and accompanied social and economical burdens. In seeking to ameliorate ageing and age-related diseases, the search for anti-ageing drugs has been of much interest. Numerous studies have shown that the plant polyphenol, resveratrol (3,5,4'-trihydroxystilbene), extends the lifespan of several species, prevents age-related diseases, and possesses anti-inflammatory, and anti-cancer properties. The beneficial effects of resveratrol are believed to be associated with the activation of a longevity gene, SirT1. In this review, we discuss the pathogenesis of age-related neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and cerebrovascular disease. The therapeutic potential of resveratrol, diet and the roles of stem cell therapy are discussed to provide a better understanding of the ageing mystery. PMID: 20732460 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
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