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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 29, 2008 Accepted March 5, 2009 Revascularization of ischemic limbs after transplantation of human bone marrow cells with high aldehyde dehydrogenase activity Benjamin J. Capoccia, Debra L. Robson, Krysta D. Levac, Dustin J. Maxwell, Sarah A. Hohm, Marian J. Neelamkavil, Gillian I. Bell, Anargyros Xenocostas, Daniel C. Link, David Piwnica-Worms, Jan A. Nolta, and David A. Hess* Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, United States 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, Ontario, Canada Department of Developmental Biology, Molecular Imagaing Center, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States Division of Hematology, Department of Medicine, University of Western Ontario and the London Health Sciences Centre, London, Ontario, Canada Stem Cell Program, Department of Internal Medicine, University of California, Davis, Sacramento, CA, United States * Corresponding author; email: dhess{at}robarts.ca. The development of cell therapies to treat peripheral vascular disease has proven difficult due to the contribution of multiple cell types that co-ordinate revascularization. Here, 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 non-hematopoietic 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 to recipients injected with unpurified nucleated cells containing the equivalent of 2-4-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 the ischemic region 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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