|  |  |  | | | | | TERMSC | | | | | | | | | | | | | | | | | | | Reduced ischemic brain injury by partial rejuvenation of bone marrow cells in aged rats. J Cereb Blood Flow Metab. 2010 Sep 22; Authors: Taguchi A, Zhu P, Cao F, Kikuchi-Taura A, Kasahara Y, Stern DM, Soma T, Matsuyama T, Hata R Circulating bone marrow-derived immature cells, including endothelial progenitor cells, have been implicated in homeostasis of the microvasculature. Decreased levels of circulating endothelial progenitor cells, associated with aging and/or cardiovascular risk factors, correlate with poor clinical outcomes in a range of cardiovascular diseases. Herein, we transplanted bone marrow cells from young stroke-prone spontaneously hypertensive rats (SHR-SP) into aged SHR-SP, the latter not exposed to radiation or chemotherapy. Analysis of recipient peripheral blood 28 days after transplantation revealed that 5% of circulating blood cells were of donor origin. Cerebral infarction was induced on day 30 posttransplantation. Animals transplanted with bone marrow from young SHR-SP displayed an increase in density of the microvasculature in the periinfarction zone, reduced ischemic brain damage and improved neurologic function. In vitro analysis revealed enhanced activation of endothelial nitric oxide synthase and reduced activation p38 microtubule-associated protein (MAP) kinase, the latter associated with endothelial apoptosis, in cultures exposed to bone marrow-derived mononuclear cells from young animals versus cells from aged counterparts. Our findings indicate that partial rejuvenation of bone marrow from aged rats with cells from young animals enhances the response to ischemic injury, potentially at the level of endothelial/vascular activation, providing insight into a novel approach ameliorate chronic vascular diseases.Journal of Cerebral Blood Flow & Metabolism advance online publication, 22 September 2010; doi:10.1038/jcbfm.2010.165. PMID: 20859292 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Stem Cells and Burns: Review and Therapeutic Implications. J Burn Care Res. 2010 Sep 20; Authors: Butler KL, Goverman J, Ma H, Fischman A, Yu YM, Bilodeau M, Rad AM, Bonab AA, Tompkins RG, Fagan SP Despite significant advances in burn resuscitation and wound care over the past 30 years, morbidity and mortality from thermal injury remain high. Limited donor skin in severely burned patients hinders effective wound excision and closure, leading to infectious complications and prolonged hospitalizations. Even with large-volume fluid resuscitation, the systemic inflammatory response syndrome compromises end-organ perfusion in burn patients, with resultant multiorgan failure. Stem cells, which enhance wound healing and counteract systemic inflammation, now offer potential therapies for these challenges. Through a review of the literature, this article seeks to illustrate applications of stem cell therapy to burn care and to highlight promising areas of research. PMID: 20859216 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The future of regenerating the myocardium. Curr Opin Cardiol. 2010 Sep 21; Authors: Kuraitis D, Suuronen EJ, Sellke FW, Ruel M PURPOSE OF REVIEW: Stem cell therapy for cardiac disease may be facing two major problems nowadays: although vasculogenesis likely occurs as a result of cell therapy, its clinical applications are limited and significant, integrated cardiomyogenesis has not demonstratively been shown to occur, even in the experimental setting, with any other source than embryonic or other pluripotent stem cells. RECENT FINDINGS: In this article, we highlight several factors that will need to be optimized if we are to achieve clinically effective cardiomyogenesis, such as the identification of optimal stem cell populations, and the ideal time and methods for cell transplantation. So far, educated attempts at achieving transplanted stem cell-induced myogenesis have largely failed outside of the embryonic stem cell realm, and we present the rationale for also considering acellular techniques, which may enhance the potential of endogenous progenitor populations. SUMMARY: In today's cardiovascular field, once a cardiomyocyte is lost it is lost for good, without any form of direct therapeutic option. For these reasons, cell therapy justifies our continued attention and efforts, and may constitute the holy grail of cardiovascular therapeutics. PMID: 20859204 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Epidermal Growth Factor Receptor Expression Identifies Functionally and Molecularly Distinct Tumor-Initiating Cells in Human Glioblastoma Multiforme and Is Required for Gliomagenesis. Cancer Res. 2010 Sep 21; Authors: Mazzoleni S, Politi LS, Pala M, Cominelli M, Franzin A, Sergi Sergi L, Falini A, De Palma M, Bulfone A, Poliani PL, Galli R Epidermal growth factor receptor (EGFR) is a known diagnostic and, although controversial, prognostic marker of human glioblastoma multiforme (GBM). However, its functional role and biological significance in GBM remain elusive. Here, we show that multiple GBM cell subpopulations could be purified from the specimens of patients with GBM and from cancer stem cell (CSC) lines based on the expression of EGFR and of other putative CSC markers. All these subpopulations are molecularly and functionally distinct, are tumorigenic, and need to express EGFR to promote experimental tumorigenesis. Among them, EGFR-expressing tumor-initiating cells (TIC) display the most malignant functional and molecular phenotype. Accordingly, modulation of EGFR expression by gain-of-function and loss-of-function strategies in GBM CSC lines enhances and reduces their tumorigenic ability, respectively, suggesting that EGFR plays a fundamental role in gliomagenesis. These findings open up the possibility of new therapeutically relevant scenarios, as the presence of functionally heterogeneous EGFR(pos) and EGFR(neg) TIC subpopulations within the same tumor might affect clinical response to treatment. Cancer Res; 70(19); 7500-13. ©2010 AACR. PMID: 20858720 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Review: Stem Cells and Gene Therapy. Lab Hematol. 2010 Sep 1;16(3):53-73 Authors: Alenzi FQ, Lotfy M, Tamimi WG, Wyse RK Both stem cell and gene therapy research are currently the focus of intense research in institutions and companies around the world. Both approaches hold great promise by offering radical new and successful ways of treating debilitating and incurable diseases effectively. Gene therapy is an approach to treat, cure, or ultimately prevent disease by changing the pattern of gene expression. It is mostly experimental, but a number of clinical human trials have already been conducted. Gene therapy can be targeted to somatic or germ cells; the most common vectors are viruses. Scientists manipulate the viral genome and thus introduce therapeutic genes to the target organ. Viruses, in this context, can cause adverse events such as toxicity, immune and inflammatory responses, as well as gene control and targeting issues. Alternative modalities being considered are complexes of DNA with lipids and proteins.Stem cells are primitive cells that have the capacity to self renew as well as to differentiate into 1 or more mature cell types. Pluripotent embryonic stem cells derived from the inner cell mass can develop into more than 200 different cells and differentiate into cells of the 3 germ cell layers. Because of their capacity of unlimited expansion and pluripotency, they are useful in regenerative medicine. Tissue or adult stem cells produce cells specific to the tissue in which they are found. They are relatively unspecialized and predetermined to give rise to specific cell types when they differentiate. The current review provides a summary of our current knowledge of stem cells and gene therapy as well as their clinical implications and related therapeutic options. PMID: 20858588 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The use of micropatterning to control smooth muscle myosin heavy chain expression and limit the response to transforming growth factor β1 in vascular smooth muscle cells. Biomaterials. 2010 Sep 19; Authors: Williams C, Brown XQ, Bartolak-Suki E, Ma H, Chilkoti A, Wong JY In the healthy artery, contractile vascular smooth muscle cells (VSMCs) have an elongated shape and are highly aligned but transition to a synthetic phenotype in culture, while additionally becoming well spread and randomly organized. Thus, controlling VSMC phenotype is a challenge in tissue engineering. In this study, we investigated the effects of micropatterning on contractile protein expression in VSMCs at low and high passage and in the presence of transforming growth factor beta 1 (TGFβ1). Micropatterning led to significantly decreased cell area, increased elongation, and increased alignment compared to non-patterned VSMCs independent of passage number. In the presence of serum, micropatterning led to increased smooth muscle myosin heavy chain (SM-MHC) and α-actin expression in low passage VSMCs, but had no effect on high passage VSMCs. Micropatterning was as effective as TGFβ1 in up-regulating SM-MHC at low passage; however, micropatterning limited VSMC response to TGFβ1 at both low and high passage. Investigation of TGFβ receptor 1 revealed higher expression in non-patterned VSMCs compared to patterned at high passage. Our studies demonstrate that micropatterning is an important regulator of SM-MHC expression in contractile VSMCs and that it may provide a mechanism for phenotype stabilization in the presence of growth factors. PMID: 20858564 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Plasticity in the synaptic number associated with neuropathic pain in the rat spinal dorsal horn: a stereological study. Neurosci Lett. 2010 Sep 18; Authors: Peng B, Lin JY, Shang Y, Yang ZW, Wang YP This study aimed to determine whether neuropathic pain is associated with a plasticity change in the number of synapses in the spinal dorsal horn. 12 normal adult SD rats were randomly divided into two groups: 7 animals were subjected to unilateral loose ligation (to induce chronic constriction injury) of the sciatic nerve (CCI group) and 5 animals subjected to unilateral sham-operation (sham-operated group). 28 days after operation, the L4-L6 segment of the spinal cord was removed, and paraffin-embedded sections were prepared and stained with Nissl's method and synaptophysin immunohistochemistry. The numbers of neurons and synapses in the spinal dorsal horn were estimated using a contemporary stereological technique-the optical disector. An 86% increase in the number (per unit length of the spinal cord) of synapses or 98% increase in the ratio between the numbers of synapses and neurons in the spinal dorsal horn was found in the middle tissue block but not in both the rostral and caudal tissue blokes cut from L4-L6 segment of the spinal cord. The results suggest that neuropathic pain, as established by the CCI model, is associated with a plasticity change in the spinal dorsal horn: increase in the number of synapses. PMID: 20858530 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | ROCK Inhibition Facilitates the Generation of Human-Induced Pluripotent Stem Cells in a Defined, Feeder-, and Serum-Free System. Cell Reprogram. 2010 Sep 21; Authors: Lai WH, Ho JC, Lee YK, Ng KM, Au KW, Chan YC, Lau CP, Tse HF, Siu CW Abstract Human-induced pluripotent stem cells (iPSCs) generated from human adult somatic cells through reprogramming hold great promises for future regenerative medicine. However, exposure of human iPSCs to animal feeder and serum in the process of their generation and maintenance imposes risk of transmitting animal pathogens to human subjects, thus hindering the potential therapeutic applications. Here, we report the successful generation of human iPSCs in a feeder-independent culture system with defined factors. Two stable human iPSC lines were established from primary human dermal fibroblasts of two healthy volunteers. These human iPSCs expressed a panel of pluripotency markers including stage-specific embryonic antigen (SSEA)-4, tumor-rejection antigen (TRA)-1-60, TRA-1-81, and alkaline phosphatase, while maintaining normal karyotypes and the exogenous reprogramming factors being silenced. In addition, these human iPSCs can differentiate along lineages representative of the three embryonic germ layers upon formation of embryoid bodies, indicating their pluripotency. Furthermore, subcutaneous transplantation of these cells into immunodeficient mice resulted in teratoma formation in 6 to 8 weeks. Our findings are an important step toward generating patient-specific iPSCs in a more clinically compliant manner by eliminating the need of animal feeder cells and animal serum. PMID: 20858051 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Assessment of cellular toxicity of TiO(2) nanoparticles for cardiac tissue engineering applications. Nanotoxicology. 2010 Sep 21; Authors: Jawad H, Boccaccini AR, Ali NN, Harding SE Abstract Because of the increased use of titanium dioxide (TiO(2)) nanoparticles (NPs) in tissue engineering (TE), and in new constructs for cardiac TE, their effect was studied on three relevant cell types: Adult rat ventricular cardiomyocytes, human embryonic stem cell-derived cardiomyocytes (hESC-CM) and fibroblasts. For adult rat myocytes, 10 μg/mL TiO(2) NPs showed no significant effect on myocyte survival over 24 h or acute myocyte contractility. Increasing the concentration to 100 μg/mL was seen to reduce contraction amplitude (p < 0.05). For hESC-CM, 10 μg/mL TiO(2) reduced the beating rate significantly by 24 h. No arrhythmias or cessation of beating were observed in either cell type. Culturing fibroblasts in 5-150 μg/mL TiO(2) significantly reduced cell proliferation at day 4 and increased cell death. We conclude that there may be modest but potentially adverse effects of TiO(2) NPs if used in fast degrading polymers for myocardial tissue engineering (MTE) applications. PMID: 20858044 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Stromal stem cells from adipose tissue and bone marrow of age matched female donors display distinct immunophenotypic profiles. J Cell Physiol. 2010 Sep 20; Authors: Pachón-Peña G, Yu G, Tucker A, Wu X, Vendrell J, Bunnell B, Gimble J Adipose tissue is composed of lipid-filled mature adipocytes and a heterogeneous stromal vascular fraction (SVF) population of cells. Similarly, the bone marrow (BM) is composed of multiple cell types including adipocytes, hematopoietic, osteoprogenitor, and stromal cells necessary to support hematopoiesis. Both adipose and BM contain a population of mesenchymal stromal/stem cells with the potential to differentiate into multiple lineages, including adipogenic, chondrogenic, and myogenic cells, depending on the culture conditions. In this study we have shown that human adipose derived stem cells (ASCs) and bone marrow mesenchymal stem cells (BMSCs) populations display a common expression profile for many surface antigens, including CD29, CD49c, CD147, CD166, and HLA-abc. Nevertheless, significant differences were noted in the expression of CD34 and its related protein, PODXL, CD36, CD 49f, CD106, and CD146. Furthermore, ASCs displayed more pronounced adipogenic differentiation capability relative to BMSC based on Oil Red staining (7 vs. 2.85 fold induction). In contrast, no difference between the stem cell types was detected for osteogenic differentiation based on Alizarin Red staining. Analysis by RT-PCR demonstrated that both the ASC and BMSC differentiated adipocytes and osteoblast displayed a significant upregulation of lineage specific mRNAs relative to the undifferentiated cell populations; no significant differences in fold mRNA induction was noted between ASCs and BMSCs. In conclusion, these results demonstrate human ASCs and BMSCs display distinct immunophenotypes based on surface positivity and expression intensity as well as differences in adipogenic differentiation. The findings support the use of both human ASCs and BMSCs for clinical regenerative medicine. J. Cell. Physiol. © 2010 Wiley-Liss, Inc. PMID: 20857424 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Integrin alpha 6 regulates glioblastoma stem cells. Cell Stem Cell. 2010 May 7;6(5):421-32 Authors: Lathia JD, Gallagher J, Heddleston JM, Wang J, Eyler CE, Macswords J, Wu Q, Vasanji A, McLendon RE, Hjelmeland AB, Rich JN Cancer stem cells (CSCs) are a subpopulation of tumor cells suggested to be critical for tumor maintenance, metastasis, and therapeutic resistance. Prospective identification and targeting of CSCs are therefore priorities for the development of novel therapeutic paradigms. Although CSC enrichment has been achieved with cell surface proteins including CD133 (Prominin-1), the roles of current CSC markers in tumor maintenance remain unclear. We examined the glioblastoma stem cell (GSC) perivascular microenvironment in patient specimens to identify enrichment markers with a functional significance and identified integrin alpha6 as a candidate. Integrin alpha6 is coexpressed with conventional GSC markers and enriches for GSCs. Targeting integrin alpha6 in GSCs inhibits self-renewal, proliferation, and tumor formation capacity. Our results provide evidence that GSCs express high levels of integrin alpha6, which can serve not only as an enrichment marker but also as a promising antiglioblastoma therapy. PMID: 20452317 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Making the case for private cord blood banking: mission failed! Comment to Hollands and McCauley, Stem Cell Rev and Rep 2009;5:195-203. Stem Cell Rev. 2010 Jun;6(2):234-6 Authors: Schmidt AH, Platz A, Rutt C, Ehninger G PMID: 20174980 [PubMed - indexed for MEDLINE] | | | | | | | | | |  | |  | |  |
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