Moraga Biotech Blog http://moragabiotech.com/nucleus/ en-us Nucleus CMS v3.23 © Weblog http://backend.userland.com/rss http://moragabiotech.com/nucleus//nucleus/nucleus2.gif Moraga Biotech Blog http://moragabiotech.com/nucleus/ p53-Facilitate miR-199a-3p Regulates Somatic Cell Reprogramming http://moragabiotech.com/nucleus/index.php?itemid=1319 Stem Cells, J. Wang et al. from the University of Science and Technology of China (Hefei, China) reported their experimental findings on the underlying mechanism in which the tumor suppressor gene, p53, inhibits reprogramming efficiencies in generating induced pluripotent stem cells (iPSCs) from somatic cells. The investigators found that the microRNA, miR-199a-3p, is upregulated by p53 at the post-transcriptional level. The experimental data showed that induction of miR-199a-3p significantly reduced reprogramming efficiencies as well as inhibiting cell proliferation through G1 cell cycle arrest. Conversely, inhibiting miR-199a-3p expression increased cell proliferation and reprogramming efficiencies. Additionally, the researchers demonstrated that enhanced reprogramming in p53 knockdown cells is reversed with miR-199a-3p. The authors concluded that their experimental observations suggest that miR-199a-3p could serve "as a novel p53 target that negatively regulates somatic cell reprogramming.]]> Reprogramming http://moragabiotech.com/nucleus/index.php?itemid=1319 Tue, 15 May 2012 07:34:00 -0700 Adipose Tissue -Derived Stem Cell-Seeded Small Intestinal Submucosa for Tunica Albuginea Grafting and Reconstruction http://moragabiotech.com/nucleus/index.php?itemid=1318 PNAS, L. Ma et al. from Tulane University Health Sciences Center published their study results on the feasibility of seeding rat adipose tissue-derived stem cells (ADSCs) onto rat small intestinal submucosa (SIS) for tunica albuginea (TA) reconstruction. The investigators reported that by seeding ADSCs onto SIS resulted in significant cavernosal tissue preservation while maintaining erectile responses. The experimental data revealed that the engraftment of of SIS-ADSC resulted in an increase in TGF-β1 and FGF-2 expression levels concomitant with 40% increase in mean diameter of both flaccid and erectile states. SIS grafting was found to induce upregulation of iNOS as well as downregulation of endolthelial NOS, neuronal NOS, and VEGF. However, endolthelial NOS, neuronal NOS, and VEGF expression levels were restored to normal with the seeding ADSCS on SIS grafts. The authors concluded that their study results show that "rats undergoing TA incision with autologous SIS-ADSC grafts maintained better erectile function compared with animals grafted with SIS alone." ]]> Tissue Regeneration http://moragabiotech.com/nucleus/index.php?itemid=1318 Mon, 14 May 2012 18:56:00 -0700 Antiangiogenic Agents increase Breast Cancer Stem Cells via the Generation of Tumor Hypoxia http://moragabiotech.com/nucleus/index.php?itemid=1317 PNAS, S. J. Conley et al. from the University of Michigan published their experimental results on antiangiogenic agents enhancing the invasive and metastatic properties of breast cancer cells. The investigators found that antiangiogenic agents such as sunitinib and bevacizumab increased a subpopulation human breast cancer cells as a result of generating intratumoral hypoxia. In vitro studies revealed that hypoxia drives stem cell enrichment which is mediated by hypoxia-inducible factor-1α (HF-1α). The researchers also conducted experiments to demonstrate that Akt/β-catenin regulatory pathway is activated under hypoxic conditions. The authors concluded that "hypoxia-driven cancer stem cell stimulation limits the effectiveness of antiangiogenic agents, and suggest that to improve patient outcome, these agents might have to be combined with cancer stem cell-targeting drugs."]]> Stem Cells and Cancer http://moragabiotech.com/nucleus/index.php?itemid=1317 Fri, 11 May 2012 07:41:00 -0700 Mesenchymal Stem Cell-Induced Immunoregulation Involves FAS-Ligand-/FAS-Mediated T Cell Apoptosis http://moragabiotech.com/nucleus/index.php?itemid=1316 Cell Stem Cell, K. Akiyama et al. from the University of Southern California School of Dentistry reported their study results on the immunosuppressive effects of bone marrow-derived mesenchymal stem cells (BMMSCs) when systemically infused into mice. The investigators found that that infusion of BMMSC induced transient T cell apoptosis via the FAS ligand (FASL)-dependent FAS pathway. In animal models, BMMSCs infusion ameliorated fibrillin-1 mutated systemic scelerosis and dextran-induced experimental colitis. BMMSCs derived from null mice (FASL-/-) were not able to induce T cell apoptosis in recipient mice. The experimental data revealed that BMMSCs secreted a FAS-regulated monocytic protein (MCP-1) which recruited T cells for FASL-mediated apoptosis. Additionally, apoptotic T cells triggered macrophages to produce TGFβ which subsequently upregulated Tregs (CD4+,CD25+, Foxp3+) and induced immune tolerance. The authors concluded that their experimental data "demonstrate a previously unrecognized mechanism underlying BMMSC-based immunotherapy involving coupling via FAS/FASL to induce T cell apoptosis."]]> Signaling and Pathways http://moragabiotech.com/nucleus/index.php?itemid=1316 Thu, 10 May 2012 07:32:00 -0700 Human Induced Pluripotent Stem Cells form Functional Neurons and Improve Recovery after Grafting in Stroke-Damaged Brain http://moragabiotech.com/nucleus/index.php?itemid=1315 Stem Cells, K. Oki et al. from University Hospital (Lund, Sweden) published their study results on long-term, self-renewing neuroepithelial stem cells (lt-NESCs) derived from adult human fibroblast-derived induced pluripotent stem cells (iPSCs). One week after transplantation of the lt-NES into an experimentally-induced mouse stroke model and in the rat striatum or cortex, the investigators observed recovery of forepaw movements. The researchers surmised that because of the short time period, functional improvement was not attributed to neuronal replacement but more than likely associated with an increase in vascular endolthelial growth factor (VEGF) levels which enhanced "endogenous plasticity." Four months after transplantation, the lt-NESCs stop proliferating and differentiated into mature neurons without forming tumors. The grafted cells formed axonal projections and exhibited electrophysiological properties of mature neurons. The authors concluded that their study "provides the first evidence that transplantation of human iPSC-derived cells is a safe and efficient approach to promote recovery after stroke and can be used to supply the injured brain with new neurons for replacement."]]> Reprogramming http://moragabiotech.com/nucleus/index.php?itemid=1315 Wed, 9 May 2012 18:46:00 -0700 Erosion of Dosage Compensation Impact Human iPSC Disease Modeling http://moragabiotech.com/nucleus/index.php?itemid=1314 published in the May 4th issue of Cell Stem Cell their study results on epigenetic variations human induced pluripotent stem cell (hiPSC) lines. The investigators foud that low-passage female hiPSCs over time undergo transcriptional derepression of the inactive X chromosome (XCI). Erosion of X inactivation is reflected in the loss of both XIST expression and H3-K27 trimethylation. The researchers noted that erosion of XCI can significantly impact disease modeling such as Lesch-Nyhan syndrome when using female hiPSCs. The experimental also revealed that erosion of gene dosage compensation affects most X-linked loci in female iPSCs and hESC lines.]]> Reprogramming http://moragabiotech.com/nucleus/index.php?itemid=1314 Tue, 8 May 2012 07:53:00 -0700 Short-term Calorie Restriction Enhances Skeletal Muscle Stem Cell Function http://moragabiotech.com/nucleus/index.php?itemid=1313 Cell Stem Cell, M. Cerlettie et al. from Harvard University Stem Cell Institute reported their study results on the underlying mechanism in which calorie restriction (CR) extends the life span of mammals. With a mouse skeletal muscle model, the investigators found that CR can significantly enhance stem cell availability in both young and old animals. The data revealed CR induced mitochondrial genesis concomitant with upregulation of conserved metabolic and longevity regulators. CR also induce endogenous muscle repair and improved satellite cell function in regenerating muscle follow transplantation. The authors concluded that their experimental observation "indicate that metabolic factors play a critical role in regulating stem cell function and that this regulation can influence the efficacy of recovery from injury and the engraftment of transplanted cells."]]> Tissue Regeneration http://moragabiotech.com/nucleus/index.php?itemid=1313 Mon, 7 May 2012 07:51:00 -0700 Cdc42 Activity Regulates Hematopoietic Stem Cell Aging and Rejuventation http://moragabiotech.com/nucleus/index.php?itemid=1312 Cell Stem Cell, M. C. Florian et al. from the University of Ulm (Ulm, Germany) published the results of their study in determining underlyig molecular mechanisms involving a decline hematopoietic function concomitant with a reduction in the immune response during aging. The authors noted that associated with a progressive decline in the immune system is an increase in the incidence of myeloid malignancy. The researchers found that there is a constitutively increase in the activity of RhoGTPase Cdc42 which causes aging of young hemapoietic stem cells (HSCs). The experimental data also revealed that elevated Cdc42 activity correlates with a loss of cell polarity in aged HSCs. Conversely, drug-induced inhibition of Cdc42 activity rejuvenates aged HSC while restoring the level and spatial distribution histone4 16 acetylation to levels observed in young HSCs. Ther authors concluded that their study observations "suggest a mechanistic role for Cdc42 activity in HSC biology and epigenetic regulation, and identify Cdc42 activity as a pharmacological target for ameliorating stem cell aging."]]> Signaling and Pathways http://moragabiotech.com/nucleus/index.php?itemid=1312 Fri, 4 May 2012 20:42:00 -0700 Elf5 Regulates Mammary Gland Stem/Progenitor Cell Faby by Influencing Notch Signaling http://moragabiotech.com/nucleus/index.php?itemid=1311 Stem Cells, R. Chakrabarti et al. from State University of New York at Buffalo reported their study results on the role of the transcription factor, Elf5, in regulating mammary gland development. The investigators found that in Elf5-null mice there was a lack of alveologenesis in the mammary gland during pregnancy. The experimental data also showed that Elf5 regulated genes in the JAK/STAT pathway which appears to regulate terminal differentiation of alvelolar cells. Targeted deletion of Elf5 lead to an accuulation of luminal progenitors co-expressing K8 and K14 as well as CD61. This observation suggested that Elf5 regulated differentiation of the progenitor cells. Additionally, Elf5 deficiency resulted in an increase in adult mammary stem activity which was revealed by an enriched population in both virgin and pregnant mice. The authors noted that their "our biochemical studies suggest that Elf5 loss leads to hyperactivation of the Notch signaling pathway, which might constitute in part, the underlying molecular mechanism for the altered cell lineage decisions in Elf5-null mammary epithelial cells."]]> Signaling and Pathways http://moragabiotech.com/nucleus/index.php?itemid=1311 Thu, 3 May 2012 18:50:17 -0700 Restricted Myogenic Potential of Mesecnhymal Stromal Cells Isolated from Umbilical Cord http://moragabiotech.com/nucleus/index.php?itemid=1310 Cell Transplantation, I. Grabowska et al. from the University of Warsaw (Poland) reported their study results on the myogenic potential of mesenchymal stromal cells isolated from Wharton's jelly. The invedtigators conducted experiments demonstrating that a subpopulation of mononucleated cells from the umbilical cord expressed pluripotent and myogenic markers. In vitro experiments revealed that these isolated mesenchymal stromal cells were able to differentiate into a myogenic lineage which was supported by co-culturing with C2C12 myoblasts. In vivo experiments showed that the mesenchymal cells participated in the formation of new muscle fibers. Interestingly, pretreatment with SDF-1 did not enhance mesenchymal cells in regenerating muscle fibers, but they did impact increased muscle mass.]]> Isolation and Characterization http://moragabiotech.com/nucleus/index.php?itemid=1310 Wed, 2 May 2012 22:46:29 -0700
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