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

Joanna Bukowska, Andrea Alarcon Uquillas, Xiying Wu, Trivia Frazier, Katarzyna Walendzik, Mikaela Vanek, DIna Gaupp, Bruce A. Bunnell, Paul Kosnik, Babak Mehrara, Adam J. Katz, Barbara Gawronska-Kozak, Jeffrey M. Gimble

Research output: Contribution to journalArticle

2 Scopus citations

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.

Original languageEnglish
Pages (from-to)440-451
Number of pages12
JournalStem Cells and Development
Volume29
Issue number7
DOIs
StatePublished - 1 Apr 2020

Keywords

  • adipose-derived stromal/stem cells (ASCs)
  • dermal fibroblast cells (DFC)
  • pressure ulcer (PU)
  • stromal vascular fraction (SVF) cells

Fingerprint Dive into the research topics of 'Safety and Efficacy of Human Adipose-Derived Stromal/Stem Cell Therapy in an Immunocompetent Murine Pressure Ulcer Model'. Together they form a unique fingerprint.

  • Cite this

    Bukowska, J., Alarcon Uquillas, A., Wu, X., Frazier, T., Walendzik, K., Vanek, M., Gaupp, DI., Bunnell, B. A., Kosnik, P., Mehrara, B., Katz, A. J., Gawronska-Kozak, B., & Gimble, J. M. (2020). Safety and Efficacy of Human Adipose-Derived Stromal/Stem Cell Therapy in an Immunocompetent Murine Pressure Ulcer Model. Stem Cells and Development, 29(7), 440-451. https://doi.org/10.1089/scd.2019.0244