Abstract
ObjectiveMesenchymal stromal cells (MSCs) expanded in vitro have been proposed as a potential therapy for congenital or acquired skin defects in pediatrics. The aim of this pre-clinical study was to investigate the effects of intradermal injections of MSC in experimental cutaneous wound repair comparing allogeneic and autologous adipose stem cells (ASCs) and autologous bone marrow-mesenchymal stromal cells (BM-MSCs).MethodsMesenchymal stromal cells were in vitro expanded from adipose and BM tissues of young female New Zealand rabbits. MSCs were characterized for plastic adhesion, surface markers, proliferation and differentiation capacity. When an adequate number of cells (ASCs 10 × 106 and BM-MSCs 3 × 106, because of their low rate of proliferation) was reached, two skin wounds were surgically induced in each animal. The first was topically treated with cell infusions, the second was used as a control. The intradermal inoculation included autologous or allogeneic ASCs or autologous BM-MSCs. For histological examination, animals were sacrificed and wounds were harvested after 11 and 21 days of treatment.ResultsRabbit ASCs were isolated and expanded in vitro with relative abundance, cells expressed typical surface markers (CD49e, CD90 and CD29). Topically, ASC inoculation provided more rapid wound healing than BM-MSCs and controls. Improved re-epithelization, reduced inflammatory infiltration and increased collagen deposition were observed in biopsies from wounds treated with ASCs, with the best result in the autologous setting. ASCs also improved restoration of skin architecture during wound healing.ConclusionThe use of ASCs may offer a promising solution to treat extended wounds. Pre-clinical studies are however necessary to validate the best skin regeneration technique, which could be used in pediatric surgical translational research.
Highlights
Renewal and maintenance of normal skin depend on a pool of endogenous progenitors
adipose stem cells (ASCs) and bone marrow (BM)‐Mesenchymal stromal cells (MSCs) expansion rate and intradermal inoculation ASCs were isolated from all rabbits and expanded to P4, while bone marrow-mesenchymal stromal cells (BM-MSCs) were isolated and expanded to P3 in 4 out of 27 rabbits
The time to reach confluence was longer for BM-MSC than ASC
Summary
A series of coordinated events occur, including bleeding and coagulation, acute inflammation, cell migration, proliferation, differentiation, angiogenesis, re-epithelialization, and synthesis as well as remodelling of the extracellular matrix These complex events involve three overlapping phases: inflammation, proliferation and remodelling [1,2,3,4]. These multipotent cells with innate selfrenewal capacity can be in vitro expanded without losing their differentiation potential. MSCs have been isolated from various tissues such as bone marrow (BM), umbilical cord blood, skeletal muscle and brain They can be obtained in large quantities with minimal invasiveness from adipose tissue, the so called adipose stem cells (ASCs) [14, 15]. It has been demonstrated that human ASCs support hematopoiesis both in vitro and in vivo more efficiently than human BM-MSCs, on the other hand it has been suggested that BM-MSCs evoke less inflammation and thrombogenesis than ASC [16]
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