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Autologous Adipose Stromal Cells Seeded onto a Human Collagen Matrix for Dermal Regeneration in Chronic Wounds: Clinical Proof of Concept

Lafosse, Aurore M.D.; Desmet, Céline M.Sc.; Aouassar, Najima B.Sc.; André, Wivine M.Sc.; Hanet, Marie-Sophie M.D.; Beauloye, Christophe M.D., Ph.D.; Vanwijck, Romain M.D., Ph.D.; Poirel, Hélène A. M.D., Ph.D.; Gallez, Bernard Ph.D.; Dufrane, Denis M.D., Ph.D.

Plastic and Reconstructive Surgery: August 2015 - Volume 136 - Issue 2 - p 279–295
doi: 10.1097/PRS.0000000000001437
Experimental: Original Articles
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Background: Nonhealing wounds are unable to integrate skin autografts by avascular and fibrotic dermal tissue. Adipose-derived stromal cells can improve the local environment of the wound bed by angiogenesis and immunomodulation. This work aimed to develop a biological dressing made of adipose-derived stromal cells onto a human acellular collagen matrix.

Methods: Adipose-derived stromal cells were isolated from human adipose tissue (n = 8). In vitro, the genetic stability during early and late passages (1, 4, 10, and 16) and vascular endothelial growth factor (VEGF) secretion were assessed. Adipose-derived stromal cell adhesion and spreading on collagen matrix were preliminarily studied. In vivo tumorigenicity, angiogenesis, and tissue oxygenation were assessed after implantation of the construct in nude rats (n = 10). The biological dressing was manufactured and implanted in three patients with chronic wounds.

Results: In vitro, aneuploidies, but no clonal transformation, were detected up to late cellular passages. VEGF was secreted more during hypoxia (0.1% oxygen) than during normoxia (21% oxygen). Adipose-derived stromal cells can adhere and spread on the scaffold within 18 to 20 days. No tumor development occurred 3 months after implantation in immunocompromised rats. Vessel counts and tissue oxygenation were higher after adipose-derived stromal cell implantation. In patients, granulation tissue was found (276 percent of vessel density), followed by epithelialization or split-thickness skin engraftment up to 22 months after implantation.

Conclusions: Implantation of adipose-derived stromal cells seeded onto human acellular collagen matrix (biological dressing) represents a promising therapy for nonhealing wounds, offering improvement in dermal angiogenesis and remodeling. This therapy using autologous stromal cells is safe, without significant genetic alterations after in vitro expansion.

Brussels, Belgium

From the Endocrine Cell Therapy Unit, Center of Tissue/Cell Therapy, Institut de Recherche Expérimentale et Clinique, Plastic and Reconstructive Surgery Unit, Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Unit, Center for Human Genetics and Human Molecular Genetics, de Duve Institute, Cliniques Universitaires Saint-Luc, Cardiovascular Research Unit, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain.

Received for publication October 24, 2014; accepted February 12, 2015.

Presented at the European Association of Plastic Surgeons Research Council, in Munich, Germany, May 23 through 24, 2012; the 21st Annual Congress of the European Association of Tissue Banks, in Vienna, Austria, November 21 through 23, 2012; the Spring Meeting of the Royal Belgian Society for Plastic Surgery, in Liège, Belgium, April 27, 2013; and the 11th Annual Meeting of the International Federation for Adipose Therapeutics and Science, in New York, New York, November 21 through 24, 2013.

Disclosure: The authors have no financial interest to declare in relation to the content of this article.

Denis Dufrane, M.D., Ph.D., Endocrine Cell Therapy Unit, Center of Tissue/Cell Therapy, Cliniques Universitaires Saint-Luc, Avenue Hippocrate 10, B-1200 Brussels, Belgium, denis.dufrane@uclouvain.be

©2015American Society of Plastic Surgeons