Adipose stromal/stem cells assist fat transplantation reducing necrosis and increasing graft performance

Abstract

Autologous fat transfer (AFT) is a procedure for adipose tissue (AT) repair after trauma, burns, post-tumor resections and lipodystrophies still negatively impacted by the lack of graft persistence. The reasons behind this poor outcome are unclear and seem to involve damages in either harvested/transplanted mature adipocytes or on their mesenchymal progenitors, namely adipose stromal/stem cells (ASC), and due to post-transplant AT apoptosis and involution. A rabbit subcutaneous AT regeneration model was here developed to first evaluate graft quality at different times after implant focusing on related parameters, such as necrosis and vasculogenesis. Standard AFT was compared with a strategy where purified autologous ASC, combined with hyaluronic acid (HA), assisted AFT. Five million of autologous ex vivo isolated CD29+, CD90+, CD49e+ ASC, loaded into HA, enriched 1 ml of AT generating an early significant protective effect in reducing AFT necrosis and increasing vasculogenesis with a preservation of transplanted AT architecture. This beneficial impact of ASC assisted AFT was then confirmed at three months with a robust lipopreservation and no signs of cellular transformation. By a novel ASC assisted AFT approach we ensure a reduction in early cell death favoring an enduring graft performance possibly for a more stable benefit in patients.Electronic supplementary materialThe online version of this article (doi:10.1007/s10495-013-0878-7) contains supplementary material, which is available to authorized users.

Allogeneic Adipose-Derived Stem Cells Protect Fat Grafts at the Early Stage and Improve Long-Term Retention in Immunocompetent Rats

“…The following factors influence the long-term retention of fat grafts. First, it depends on the extent of cell injury or death caused by surgeryinduced injury at the early stage of transplantation before the new blood supply of the graft is established [10,25]. Using Perilipin A immunofluorescence staining and the TUNEL assay, this study demonstrated that syngeneic ASCs can alleviate injury and reduce apoptosis, which is consistent with findings of other investigators [10,26].…”

“…Therefore, the longterm retention of fat grafts was our first concern in this study. Graft volume continues to decline until 3 months post-transplantation [22], and therefore the third month post-transplantation was regarded as the most appropriate time point to measure the long-term volume retention of fat grafts in small animal models, which are consistent with previous studies [10,23,24]. The following factors influence the long-term retention of fat grafts.…”

“…To solve the problem of high absorption rates, Yoshimura et al first used CAL in 2006. Using this approach, ASCs were able to resist injury [10,13] and promote neovascularization of fat grafts [14,15].…”

“…Sections were then counterstained with DAPI (Sigma). The percentage of positive cells in the grafts was calculated on 5 randomly selected fields from each specimens (n = 5/specimen) [10].…”

The promising role for adipose-derived mesenchymal stem cells in tissue regeneration

“…This immunosuppression of T lymphocytes was also demonstrated to reduce the severity of symptoms in rheumatoid arthritis [60]. ASCs were also shown to decrease the incidence of necrosis following autologous fat grafting [114]. Through the upregulation of VEGF and IL-10, intracerebral implantation of ASCs demonstrated significantly improved functional outcomes in a mouse model of Alzheimer's disease [115].…”