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Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration

Nature Medicine volume 9, pages 702–712 (2003)Cite this article

Abstract

Emerging evidence suggests that bone marrow–derived endothelial, hematopoietic stem and progenitor cells contribute to tissue vascularization during both embryonic and postnatal physiological processes. Recent preclinical and pioneering clinical studies have shown that introduction of bone marrow–derived endothelial and hematopoietic progenitors can restore tissue vascularization after ischemic events in limbs, retina and myocardium. Corecruitment of angiocompetent hematopoietic cells delivering specific angiogenic factors facilitates incorporation of endothelial progenitor cells (EPCs) into newly sprouting blood vessels. Identification of cellular mediators and tissue-specific chemokines, which facilitate selective recruitment of bone marrow–derived stem and progenitor cells to specific organs, will open up new avenues of research to accelerate organ vascularization and regeneration. In addition, identification of factors that promote differentiation of the progenitor cells will permit functional incorporation into neo-vessels of specific tissues while diminishing potential toxicity to other organs. In this review, we discuss the clinical potential of vascular progenitor and stem cells to restore long-lasting organ vascularization and function.

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Figure 1: Phenotypic and functional identification of human and mouse endothelial progenitors.
Figure 2: Molecular switches involved in the mobilization and recruitment of endothelial, lymphatic and hematopoietic stem and progenitor cells.
Figure 3: Cross-talk between EPCs, CEPs, HSCs and HPCs.
Figure 4: Route of delivery of stem cells for tissue revascularization.
Figure 5: Ex vivo expansion of transplantable EPCs, CEPs, HSC and HPCs.

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Acknowledgements

S.R. is supported by grants from the National Heart, Lung, Blood Institute, R01 grants HL61849, HL66592, HL67839 and HL59312, American Cancer Society grant 101396 and the Leukemia and Lymphoma Society. D.L. is supported by grants from the National Institutes of Health (HL66592), the Children's Blood Foundation, the Emerald Foundation, the Ted Rapp Foundation, the Foundation for Biomedical Research of the Academy of Athens, Nicolaos Tzimas, and the American Hellenic Educational and Progressive Association V District.

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  1. Department of Hematology-Oncology and Genetic Medicine, Cornell University Medical College, New York, 10021, New York, USA

    Shahin Rafii

  2. Department of Pediatrics and the Children's Blood Foundation Laboratories, Cornell University Medical College, New York, 10021, New York, USA

    David Lyden

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Correspondence to Shahin Rafii.

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Rafii, S., Lyden, D. Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration. Nat Med 9, 702–712 (2003). https://doi.org/10.1038/nm0603-702

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