RegenMD - Gene Defects Common in Induced Stem Cells

RegenMD         Gene Defects Common in Induced Stem Cells March 2, 2011 at 2:05 PM   The road to regenerative medicine based on induced pluripotent stem cells (iPSCs) may have developed a giant pothole, with new studies showing that the cells are prone to several types of genetic defects. Point mutations, copy number variations, ... See all stories on this topic »         Tengion lands $31.4M investment March 2, 2011 at 2:05 PM   Regenerative medicine firm Tengion, which has been at risk of shutting down as it depleted its funds, has secured $31.4 million from investors. Regenerative medicine firm Tengion has secured $31.4 million in new investment financing that will allow it ... See all stories on this topic »         IL-17 and VEGF Are Necessary for Efficient Corneal Nerve Regeneration. March 2, 2011 at 10:05 AM   IL-17 and VEGF Are Necessary for Efficient Corneal Nerve Regeneration. Am J Pathol. 2011 Mar;178(3):1106-16 Authors: Li Z, Burns AR, Han L, Rumbaut RE, Smith CW The contribution of acute inflammation to sensory nerve regeneration was investigated in the murine cornea using a model of corneal abrasion that removes the stratified epithelium and subbasal nerve plexus. Abrasion induced accumulation of IL-17(+) CCR6(+) γδ T cells, neutrophils, and platelets in the cornea followed by full restoration of the epithelium and ∼19% regeneration of sensory nerves within 96 hours. Mice deficient in γδ T cells (TCRδ(-/-)) or wild-type mice treated systemically with anti-IL-17 had >50% reduction in leukocyte and platelet infiltration and >50% reduction in nerve regeneration. Strategies used to prevent neutrophil and platelet accumulation (eg, wild-type mice treated with anti-Ly6G or anti-GP1bα antibody to deplete neutrophils or platelets) also resulted in >50% reductions in corneal nerve density. Infiltrating neutrophils and platelets stained positively for VEGF-A, tissue levels of VEGF-A peaked coincidentally with peak tissue levels of neutrophils and platelets, depletion of neutrophils before injury reduced tissue VEGF-A levels by >70%, and wild-type mice treated systemically with anti-VEGF-A antibody exhibited >80% reduction in corneal nerve regeneration. Given the known trophic effects of VEGF-A for neurite growth, the results in this report demonstrate a previously unrecognized beneficial role for the γδ T cell-dependent inflammatory cascade involving IL-17, neutrophils, platelets, and VEGF-A in corneal nerve regeneration. PMID: 21356362 [PubMed - in process]         Alveolar epithelial cell therapy with human cord blood-derived hematopoietic progenitor cells. March 2, 2011 at 10:05 AM   Alveolar epithelial cell therapy with human cord blood-derived hematopoietic progenitor cells. Am J Pathol. 2011 Mar;178(3):1329-39 Authors: De Paepe ME, Mao Q, Ghanta S, Hovanesian V, Padbury JF The role of umbilical cord blood (CB)-derived stem cell therapy in neonatal lung injury remains undetermined. We investigated the capacity of human CB-derived CD34(+) hematopoietic progenitor cells to regenerate injured alveolar epithelium in newborn mice. Double-transgenic mice with doxycycline (Dox)-dependent lung-specific Fas ligand (FasL) overexpression, treated with Dox between embryonal day 15 and postnatal day 3, served as a model of neonatal lung injury. Single-transgenic non-Dox-responsive littermates were controls. CD34(+) cells (1 × 10(5) to 5 × 10(5)) were administered at postnatal day 5 by intranasal inoculation. Engraftment, respiratory epithelial differentiation, proliferation, and cell fusion were studied at 8 weeks after inoculation. Engrafted cells were readily detected in all recipients and showed a higher incidence of surfactant immunoreactivity and proliferative activity in FasL-overexpressing animals compared with non-FasL-injured littermates. Cord blood-derived cells surrounding surfactant-immunoreactive type II-like cells frequently showed a transitional phenotype between type II and type I cells and/or type I cell-specific podoplanin immunoreactivity. Lack of nuclear colocalization of human and murine genomic material suggested the absence of fusion. In conclusion, human CB-derived CD34(+) cells are capable of long-term pulmonary engraftment, replication, clonal expansion, and reconstitution of injured respiratory epithelium by fusion-independent mechanisms. Cord blood-derived surfactant-positive epithelial cells appear to act as progenitors of the distal respiratory unit, analogous to resident type II cells. Graft proliferation and alveolar epithelial differentiation are promoted by lung injury. PMID: 21356383 [PubMed - in process]             This email was sent to agupta1213+termsc@gmail.com. Delivered by Feed My Inbox PO Box 682532 Franklin, TN 37068 Account Login Unsubscribe Here