Safety and efficacy of human adipose-derived stromal/stem cell therapy in an immunocompetent murine pressure ulcer model Journal Article


Authors: Bukowska, J.; Alarcon Uquillas, A.; Wu, X.; Frazier, T.; Walendzik, K.; Vanek, M.; Gaupp, D.; Bunnell, B. A.; Kosnik, P.; Mehrara, B.; Katz, A. J.; Gawronska-Kozak, B.; Gimble, J. M.
Article Title: Safety and efficacy of human adipose-derived stromal/stem cell therapy in an immunocompetent murine pressure ulcer model
Abstract: 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. © Mary Ann Liebert, Inc., publishers 2020.
Keywords: immunohistochemistry; controlled study; human tissue; human cell; nonhuman; mouse; cell infiltration; animal experiment; stem cell transplantation; in vivo study; cell differentiation; food and drug administration; in vitro study; cell population; cell assay; dermis; histology; wound healing; cryopreservation; injection; immunophenotyping; therapy effect; safety; wound closure; immunocompetent cell; adipose tissue; skin fibroblast; cd68 antigen; colony forming unit; microphotography; colony formation; adipogenesis; point of care testing; adipose derived stem cell; human; male; female; priority journal; article; decubitus; adipose-derived stromal/stem cells (ascs); dermal fibroblast cells (dfc); pressure ulcer (pu); stromal vascular fraction (svf) cells
Journal Title: Stem Cells and Development
Volume: 29
Issue: 7
ISSN: 1547-3287
Publisher: Mary Ann Liebert, Inc  
Date Published: 2020-04-01
Start Page: 440
End Page: 451
Language: English
DOI: 10.1089/scd.2019.0244
PUBMED: 31950878
PROVIDER: scopus
PMCID: PMC7153639
DOI/URL:
Notes: Article -- Export Date: 1 May 2020 -- Source: Scopus
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  1. Babak Mehrara
    451 Mehrara