西亚试剂：Revascularization of ischemic limbs after transplantation o

发布时间：2025-09-10

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*

1 Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, United States
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, Ontario, Canada
3 Department of Developmental Biology, Molecular Imagaing Center, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States
4 Division of Hematology, Department of Medicine, University of Western Ontario and the London Health Sciences Centre, London, Ontario, Canada
5 Stem Cell Program, Department of Internal Medicine, University of California, Davis, Sacramento, CA, United States

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 (ALDH^hi) activity, a progenitor cell function conserved between several lineages. BM ALDH^hi 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 ALDH^hi 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 ALDH^hi cells, mice transplanted with purified ALDH^hi cells showed augmented recovery of perfusion and increased blood vessel density in ischemic limbs. ALDH^hi cells transiently recruited to the ischemic region but did not significantly integrate into ischemic tissue, suggesting that transient ALDH^hi cell engraftment stimulated endogenous revascularization. Thus, human BM ALDH^hi 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.

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