RESUMO
Autologous fat transplantation is a versatile tool in reconstructive surgery. Adipose-derived stem cells (ASCs) increase survival of fat grafts and thus are increasingly used for breast reconstruction in breast cancer patients. However, radiation and/or chemotherapy have been proposed to inhibit soft tissue regeneration in wound healing thus suggesting alteration in stem cell pathways. Therefore, elucidating effects of radiation and chemotherapy on ASCs is critical if one desires to enhance the survival of fat grafts in patients. This review outlines our work evaluating the function and recoverability of ASCs from radiation or chemotherapy patients, focusing specifically on their availability as a source of autologous stem cells for fat grafting and breast reconstruction in cancer patients. Even though evidence suggests radiation and chemotherapy negatively influence ASCs at the cellular level, the efficiency of the isolation and differentiation capacity did not appear influenced in patients after receiving chemotherapy treatment, although fat from radiated patients exhibited significantly altered ASC differentiation into endothelial-like cells. Further, the in vitro growth rates of patient's ASCs do not differ significantly before or after treatment. Taken together, these studies suggest ASCs as an important new tool for grafting and reconstruction even when radiation and chemotherapy treatment are involved.
RESUMO
BACKGROUND: With recent research advances, adipose-derived stromal/stem cells (ASCs) have been demonstrated to facilitate the survival of fat grafts and thus are increasingly used for reconstructive procedures following surgery for breast cancer. Unfortunately, in patients, following radiation and chemotherapy for breast cancer suggest that these cancer treatment therapies may limit stem cell cellular functions important for soft tissue wound healing. For clinical translation to patients that have undergone cancer treatment, it is necessary to understand the effects of these therapies on the ASC's ability to improve fat graft survival in clinical practice. AIM: To investigate whether the impact on ASCs function capacity and recovery in cancer patients may be due to the chemotherapy. METHODS: ASCs were isolated from the cancerous side and noncancerous side of the breast from the same patients with receiving neoadjuvant chemotherapy (NAC) or not-receiving NAC. ASCs were in vitro treated with 5-fluorouracil (5-FU), doxorubicin (DXR), and cyclophosphamide (Cytoxan) at various concentrations. The stem cells yield, cell viability, and proliferation rates were measured by growth curves and MTT assays. Differentiation capacity for adipogenesis was determined by qPCR analysis of the specific gene markers and histological staining. RESULTS: No significant differences were observed between the yield of ASCs in patients receiving NAC treatment and not-receiving NAC. ASCs yield from the cancerous side of the breast showed lower than the noncancerous side of the breast in both patients receiving NAC and not-receiving NAC. The proliferation rates of ASCs from patients didn't differ much before and after NAC upon in vitro culture, and these cells appeared to retain the capacity to acquire adipocyte traits simile to the ASCs from patients not-receiving NAC. After cessation and washout of the drugs for another a week of culturing, ASCs showed a slow recovery of cell growth capacity in 5-FU-treated groups but was not observed in ASCs treated with DXR groups. CONCLUSION: Neoadjuvant therapies do not affect the functioning capacity of ASCs. ASCs may hold great potential to serve as a cell source for fat grafting and reconstruction in patients undergoing chemotherapy.
