Safety of Human Adipose Stromal Vascular Fraction Cells Isolated with a Closed System Device in an Immunocompetent Murine Pressure Ulcer Model.

Pressure ulcers (PUs) result in part due to ischemia-reperfusion injury to the skin and present frequently in elderly or quadriplegic patients with reduced mobility. Despite the high economic and societal cost of this condition, PU therapy relies primarily on preventive strategies and invasive surgical intervention. A growing body of clinical literature suggests that localized injection of adipose-derived cells can accelerate and enhance the closure of PUs. The current study systematically evaluated the safety of human adipose stromal vascular fraction (SVF) cells isolated using a closed system device when injected into a murine PU injury model. The human SVF cells were characterized by colony-forming unit-fibroblast and differentiation assays before use. Young (2 months) immunocompetent C57BL/6 mice subjected to a magnet-induced ischemia-reperfusion injury were injected subcutaneously with human SVF cells at increasing doses (0.25-2 million cells). The size of the PU was monitored over a 20-day period. Both female and male mice tolerated the concentration-dependent injection of the SVF cells without complications. While male mice trended toward more rapid wound closure rates in response to lower SVF cell concentrations (0.25-0.5 million cells), female mice responded favorably to higher SVF cell concentrations (1-2 million cells); however, outcomes did not reach statistical significance in either sex. Overall, the study demonstrates that human SVF cells prepared with a closed system device designed for use at point of care can be safely administered for PU therapy in an immunocompetent host animal model.

Safety and Efficacy of Human Adipose-Derived Stromal/Stem Cell Therapy in an Immunocompetent Murine Pressure Ulcer Model.

Pressure injuries/ulcers are frequent complications in elderly, paraplegic, and quadriplegic patients, which account for considerable cost to the international health care economy and remain refractory to current treatment options. Autologous or allogeneic adult stromal/stem cells represent an alternative therapeutic approach. The current study extends prior findings by exploring the safety and efficacy of human adipose-derived stromal/stem cell (ASC) therapy in an established immunocompetent murine skin pressure ulcer model where dermal fibroblast cells (DFCs) served as a control. Human adipose tissue was processed using a closed system device designed for point-of-care use in the operating room and on file with the Food and Drug Administration. Cell characterization was performed using colony-forming unit-fibroblast, differentiation, and immunophenotypic assays in vitro. Wound healing was assessed over a 20-day period based on photomicrographs, histology, and immunohistochemistry. The isolated human ASCs displayed significantly greater colony formation relative to DFCs while both populations exhibited comparable immunophenotype and differentiation potential. Both fresh and cryopreserved human ASCs significantly accelerated and enhanced wound healing in young (2 month) mice of both sexes relative to DFC controls based on tissue architecture and CD68+ cell infiltration. In contrast, while injection of either fresh or cryopreserved human ASCs was safe in older mice, the fresh ASCs significantly enhanced wound closure relative to the cryopreserved ASCs. Overall, these findings support the safety and efficacy of human ASCs isolated using a closed system device designed for clinical procedures in the future treatment of pressure injuries.