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Angiogenic potential of BM MSCs derived from patients with critical leg ischemia

Bone Marrow Transplantation volume 47, pages 997–1000 (2012)Cite this article

Critical leg ischemia (CLI) is the most severe form of peripheral arterial disease and is characterized by the inability of arterial blood flow to meet the metabolic demands of resting muscle or tissue, resulting in rest pain and/or tissue necrosis, and frequently necessitating amputation. As a result of the discovery of the angiogenic potential of BM mononuclear cells (BM-MNCs), cell therapy has been proposed to treat peripheral arterial disease. The therapeutic angiogenesis by cell transplantation (TACT) study was the first trial to demonstrate a significant improvement after i.m. injection of total autologous BM-MNCs.1 In the French OPTIPEC trial (Clinical trial registration: NCT00377897), we have shown the development of a proliferative angiogenic process in the distal part of the legs in amputation specimens from patients with CLI who had received local therapeutic injections of BM-MNCs.2 Strong data from preclinical models strongly suggest that BM-MNCs do not differentiate into endothelial cells, and that their paracrine effect is most likely responsible for the angiogenic process.3 However, BM-MNCs isolated from patients with cardiovascular disease have a significantly reduced neovascularization capacity in vivo, despite similar content of hematopoietic stem cells.4 Notably, BM-MNCs contain a complex assortment of angiogenic cells, including hematopoietic progenitors as well as MSCs.

An important issue is to define, among BM-MNCs, what is the sub-population of pro-angiogenic cells that could be further isolated and expanded to develop an autologous and efficient cell therapy product. Among these cell types, MSCs, which are easily obtained in culture from BM, are potential candidates. MSCs are multipotent stem cells with the ability to differentiate into mesoderm-derived cells that exhibit immunoregulatory properties, improve hematopoietic engraftment, prevent graft failure, and reduce the incidence or severity of acute GVHD. Given their capacity to secrete angiogenic growth factors, MSCs have been proposed to improve angiogenesis, but their endothelial differentiation potential is a matter of debate. Furthermore, no data exist on the angiogenic potential of MSCs isolated from patients with peripheral arterial disease.

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Acknowledgements

C d’Audigier was supported by the Fondation pour la recherche medicale (FRM). We thank Kayle Shapiro for helpful comments and proofreading of our manuscript. This work was supported by research grants from AP-HP PHRC Optipec (03-034), Fondation pour la recherche medicale (FRM) and Fondation de France.

Author contributions: DMS designed the study, performed the research and wrote the letter. Cd’A, CLG, LM and BD performed the research. JSS designed research protocols. LDC prepared BM-MNCs. PG and JE designed the OPTIPEC study, harvested BM from CLI patients and wrote the letter.

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Authors and Affiliations

  1. Université Paris Descartes, Sorbonne Paris Cité, Paris, France

    D M Smadja, C d'Audigier, C L Guerin, L Mauge, J-S Silvestre, P Gaussem & J Emmerich

  2. INSERM UMRS 765, Faculté de Pharmacie, Paris, France

    D M Smadja, C d'Audigier, C L Guerin, L Mauge, B Dizier, P Gaussem & J Emmerich

  3. AP-HP, Hôpital Européen Georges Pompidou, Service d'Hematologie Biologique, Paris, France

    D M Smadja, C d'Audigier, L Mauge & P Gaussem

  4. Vascular Biology Program and Surgery department, Children's Hospital, Harvard Medical School, Boston, MA, USA

    D M Smadja

  5. INSERM UMRS 970, Paris Cardiovascular Research Center—PARCC, Paris, France

    C L Guerin & J-S Silvestre

  6. AP-HP, Hôpital Necker, Service de Biothérapies, Paris, France

    L Mauge & L Dal Cortivo

  7. AP-HP, Hôpital Européen Georges Pompidou, Service de Médecine Vasculaire, Paris, France

    J Emmerich

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  1. D M Smadja
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  7. L Dal Cortivo
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Correspondence to D M Smadja.

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Smadja, D., d'Audigier, C., Guerin, C. et al. Angiogenic potential of BM MSCs derived from patients with critical leg ischemia. Bone Marrow Transplant 47, 997–1000 (2012). https://doi.org/10.1038/bmt.2011.196

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