Adipose-derived stem cells mitigate deleterious effects of radiation on bone and enhance radiated fracture healing by replacing damaged cells and stimulating angiogenesis. However, adipose-derived stem cell harvest and delivery techniques must be refined to comply with the US Food and Drug Administration restrictions on implantation of cultured cells into human subjects prior to clinical translation. The purpose of this study is to demonstrate the preservation of efficacy of adipose-derived stem cells to remediate the injurious effects of radiation on fracture healing utilizing a novel harvest and delivery technique that avoids the need for cell culture. Forty-four Lewis rats were divided into 4 groups: fracture control (Fx), radiated fracture control (XFx), radiated fracture treated with cultured adipose-derived stem cells (ASC), and radiated fracture treated with noncultured minimally processed adipose-derived stem cells (MP-ASC). Excluding the Fx group, all rats received a fractionated human-equivalent dose of radiation. All groups underwent mandibular osteotomy with external fixation. Following sacrifice on postoperative day 40, union rate, mineralization, and biomechanical strength were compared between groups at P < 0.05 significance. Compared with Fx controls, the XFx group demonstrated decreased union rate (100% vs 20%), bone volume fraction (P = 0.003), and ultimate load (P < 0.001). Compared with XFx controls, the MP-ASC group tripled the union rate (20% vs 60%) and demonstrated statistically significant increases in both bone volume fraction (P = 0.005) and ultimate load (P = 0.025). Compared with the MP-ASC group, the ASC group showed increased union rate (60% vs 100%) and no significant difference in bone volume fraction (P = 0.936) and ultimate load (P = 0.202). Noncultured minimally processed adipose-derived stem cells demonstrate the capacity to improve irradiated fracture healing without the need for cell proliferation in culture. Further refinement of the cell harvest and delivery techniques demonstrated in this report will enhance the ability of noncultured minimally processed adipose-derived stem cells to improve union rate and bone quality, thereby optimizing clinical translation.
This study suggests topical DFO is capable of reducing skin ulceration and type I collagen fibril disorganization following radiotherapy. This novel application of DFO has potential to enhance expander-based breast reconstruction outcomes and improve quality of life for women suffering the devastating effects of breast cancer.
Background: Cell-based treatments have demonstrated the capacity to enhance reconstructive outcomes in recent decades but are hindered in clinical utility by regulatory hurdles surrounding cell culture. This investigation examines the ability of a noncultured stromal vascular fraction derived from lipoaspirate to enhance bone healing during fracture repair to further the development of translatable cell therapies that may improve outcomes in irradiated reconstruction. Methods: Isogenic male Lewis rats were divided into three groups: fracture, irradiated fracture, and irradiated fracture with stromal vascular fraction treatment. Irradiated groups received a fractioned dose of 35 Gy before mandibular osteotomy. Stromal vascular fraction was harvested from the inguinal fat of isogenic donors, centrifuged, and placed intraoperatively into the osteotomy site. All mandibles were evaluated for bony union and vascularity using micro–computed tomography before histologic analysis. Results: Union rates were significantly improved in the irradiated fracture with stromal vascular fraction treatment group (82 percent) compared to the irradiated fracture group (25 percent) and were not statistically different from the fracture group (100 percent). Stromal vascular fraction therapy significantly improved all metrics of bone vascularization compared to the irradiated fracture group and was not statistically different from fracture. Osteocyte proliferation and mature bone formation were significantly reduced in the irradiated fracture group. Bone cellularity and maturity were restored to nonirradiated levels in the irradiated fracture with stromal vascular fraction treatment group despite preoperative irradiation. Conclusions: Vascular and cellular depletion represent principal obstacles in the reconstruction of irradiated bone. This study demonstrates the efficacy of stromal vascular fraction therapy in remediating these damaging effects and provides a promising foundation for future studies aimed at developing noncultured, cell-based therapies for clinical implementation.
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