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 Nolta, David A. Hess

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

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. BMALDHhi cells were enriched for myeloerythroid 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 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.

Original languageEnglish (US)
Pages (from-to)5340-5351
Number of pages12
JournalBlood
Volume113
Issue number21
DOIs
StatePublished - 2009

Fingerprint

Aldehyde Dehydrogenase
Bone Marrow Transplantation
Bone
Extremities
Cells
Blood vessels
Tissue
Recovery
Transplantation
Bone Marrow Cells
Blood Vessels
Ischemia
Perfusion
Peripheral Vascular Diseases
Cell Lineage
Femoral Artery
Cell- and Tissue-Based Therapy
Ligation
Stem Cells

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Capoccia, B. J., Robson, D. L., Levac, K. D., Maxwell, D. J., Hohm, S. A., Neelamkavil, M. J., ... Hess, D. A. (2009). Revascularization of ischemic limbs after transplantation of human bone marrow cells with high aldehyde dehydrogenase activity. Blood, 113(21), 5340-5351. https://doi.org/10.1182/blood-2008-04-154567

Revascularization of ischemic limbs after transplantation of human bone marrow cells with high aldehyde dehydrogenase activity. / Capoccia, Benjamin J.; Robson, Debra L.; Levac, Krysta D.; Maxwell, Dustin J.; Hohm, Sarah A.; Neelamkavil, Marian J.; Bell, Gillian I.; Xenocostas, Anargyros; Link, Daniel C.; Piwnica-Worms, David; Nolta, Jan; Hess, David A.

In: Blood, Vol. 113, No. 21, 2009, p. 5340-5351.

Research output: Contribution to journalArticle

Capoccia, BJ, Robson, DL, Levac, KD, Maxwell, DJ, Hohm, SA, Neelamkavil, MJ, Bell, GI, Xenocostas, A, Link, DC, Piwnica-Worms, D, Nolta, J & Hess, DA 2009, 'Revascularization of ischemic limbs after transplantation of human bone marrow cells with high aldehyde dehydrogenase activity', Blood, vol. 113, no. 21, pp. 5340-5351. https://doi.org/10.1182/blood-2008-04-154567
Capoccia, Benjamin J. ; Robson, Debra L. ; Levac, Krysta D. ; Maxwell, Dustin J. ; Hohm, Sarah A. ; Neelamkavil, Marian J. ; Bell, Gillian I. ; Xenocostas, Anargyros ; Link, Daniel C. ; Piwnica-Worms, David ; Nolta, Jan ; Hess, David A. / Revascularization of ischemic limbs after transplantation of human bone marrow cells with high aldehyde dehydrogenase activity. In: Blood. 2009 ; Vol. 113, No. 21. pp. 5340-5351.
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