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Blood, 21 May 2009, Vol. 113, No. 21, pp. 5340-5351. Prepublished online as a Blood First Edition Paper on March 26, 2009; DOI 10.1182/blood-2008-04-154567. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-04-154567v1 113/21/5340    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Capoccia, B. J. Articles by Hess, D. A. Search for Related Content PubMed PubMed Citation Articles by Capoccia, B. J. Articles by Hess, D. A. Related Collections Transplantation Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  VASCULAR BIOLOGY Revascularization of ischemic limbs after transplantation of human bone marrow cells with high aldehyde dehydrogenase activity Benjamin J. Capoccia1, Debra L. Robson2, Krysta D. Levac2, Dustin J. Maxwell3, Sarah A. Hohm1, Marian J. Neelamkavil2, Gillian I. Bell2, Anargyros Xenocostas4, Daniel C. Link1, David Piwnica-Worms3, Jan A. Nolta5, and David A. Hess2 1 Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO; 2 Program in Regenerative Medicine, Krembil Centre for Stem Cell Biology, Vascular Biology Group, Robarts Research Institute, Department of Physiology and Pharmacology, University of Western Ontario, London, ON; 3 Department of Developmental Biology, Molecular Imaging Center, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO; 4 Division of Hematology, Department of Medicine, University of Western Ontario and the London Health Sciences Centre, London, ON; and 5 Stem Cell Program, Department of Internal Medicine, University of California Davis School of Medicine, Sacramento The development of cell therapies to treat peripheral vascular disease has proven difficult because of the contribution of multiple cell types that coordinate revascularization. We characterized the vascular regenerative potential of transplanted human bone marrow (BM) cells purified by high aldehyde dehydrogenase (ALDHhi) activity, a progenitor cell function conserved between several lineages. BM ALDHhi cells were enriched for myelo-erythroid progenitors that produced multipotent hematopoietic reconstitution after transplantation and contained nonhematopoietic precursors that established colonies in mesenchymal-stromal and endothelial culture conditions. The regenerative capacity of human ALDHhi cells was assessed by intravenous transplantation into immune-deficient mice with limb ischemia induced by femoral artery ligation/transection. Compared with recipients injected with unpurified nucleated cells containing the equivalent of 2- to 4-fold more ALDHhi cells, mice transplanted with purified ALDHhi cells showed augmented recovery of perfusion and increased blood vessel density in ischemic limbs. ALDHhi cells transiently recruited to ischemic regions but did not significantly integrate into ischemic tissue, suggesting that transient ALDHhi cell engraftment stimulated endogenous revascularization. Thus, human BM ALDHhi cells represent a progenitor-enriched population of several cell lineages that improves perfusion in ischemic limbs after transplantation. These clinically relevant cells may prove useful in the treatment of critical ischemia in humans. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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