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Treating Fat Grafts with Human Endothelial Progenitor Cells Promotes Their Vascularization and Improves Their Survival in Diabetes Mellitus

Hamed, Saher M.D., Ph.D.; Ben-Nun, Ohad M.D.; Egozi, Dana M.D., Ph.D.; Keren, Aviad Ph.D.; Malyarova, Nastya M.Sc.; Kruchevsky, Danny M.D.; Gilhar, Amos M.D.; Ullmann, Yehuda M.D.

Plastic and Reconstructive Surgery: October 2012 - Volume 130 - Issue 4 - p 801–811
doi: 10.1097/PRS.0b013e318262f12e
Experimental: Original Articles
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Background: Bone marrow–derived endothelial progenitor cells are required for vascularization of a fat graft to form a functional microvasculature within the graft and to facilitate its integration into the surrounding tissues. Organ transplantation carries a high risk of graft loss and rejection in patients with diabetes mellitus because endothelial progenitor cell function is impaired. The authors investigated the influence of endothelial progenitor cell treatment on the phenotype and survival of human fat grafts in immunocompromised mice with experimentally induced diabetes mellitus.

Methods: The authors injected 1 ml of human fat tissue into the scalps of 14 nondiabetic and 28 diabetic immunocompromised mice, and then treated some of the grafts with endothelial progenitor cells that were isolated from the blood of a human donor. The phenotype of the endothelial progenitor cell–treated fat grafts from the 14 diabetic mice was compared with that of the untreated fat grafts from 14 nondiabetic and 14 diabetic mice, 18 days and 15 weeks after fat transplantation. Determination of graft phenotype included measurements of weight and volume, vascular endothelial growth factor levels, vascular endothelial growth factor receptor-2, endothelial nitric oxide synthase, and caspase 3 expression levels, and histologic analysis of the extent of vascularization.

Results: The untreated grafts from the diabetic mice were fully resorbed 15 weeks after fat transplantation. The phenotype of endothelial progenitor cell–treated fat grafts from the diabetic mice was similar to that of the untreated fat grafts from the nondiabetic mice.

Conclusion: Endothelial progenitor cell treatment of transplanted fat can increase the survival of a fat graft by inducing its vascularization and decreasing the extent of apoptosis.

Haifa and Nazareth, Israel

From the Skin Research Laboratory, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology; Remedor Biomed Ltd.; and the Department of Plastic and Reconstructive Surgery, Rambam Health Care Campus.

Received for publication April 25, 2012; accepted April 27, 2012.

Disclosure:The authors have no commercial associations or financial disclosures that might pose or create a conflict of interest with information presented in this article. Remedor Biomed Ltd. financed the study and has rights to the results of the research.

Saher Hamed, M.D., Ph.D., Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, 8, Efron Street, Haifa 31000, Israel, www.saher@gmail.com

©2012American Society of Plastic Surgeons