TY - JOUR
T1 - Safety and Efficacy of Human Adipose-Derived Stromal/Stem Cell Therapy in an Immunocompetent Murine Pressure Ulcer Model
AU - Bukowska, Joanna
AU - Alarcon Uquillas, Andrea
AU - Wu, Xiying
AU - Frazier, Trivia
AU - Walendzik, Katarzyna
AU - Vanek, Mikaela
AU - Gaupp, DIna
AU - Bunnell, Bruce A.
AU - Kosnik, Paul
AU - Mehrara, Babak
AU - Katz, Adam J.
AU - Gawronska-Kozak, Barbara
AU - Gimble, Jeffrey M.
N1 - Funding Information:
Funding for the study was provided by the National Institute of Aging Phase II SBIR R44AG042904 ‘‘Adipose-Derived Stromal/Stem Cell Therapy for Pressure Ulcers.’’ J.B. visit to the Tulane University was funded by a postdoctoral fellowship from the KNOW Consortium ‘‘Healthy Animal—Safe Food,’’ MS&HE Decision No. 05-1/ KNOW2/2015.
Publisher Copyright:
© Mary Ann Liebert, Inc., publishers 2020.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - 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.
AB - 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.
KW - adipose-derived stromal/stem cells (ASCs)
KW - dermal fibroblast cells (DFC)
KW - pressure ulcer (PU)
KW - stromal vascular fraction (SVF) cells
UR - http://www.scopus.com/inward/record.url?scp=85083074032&partnerID=8YFLogxK
U2 - 10.1089/scd.2019.0244
DO - 10.1089/scd.2019.0244
M3 - Article
C2 - 31950878
AN - SCOPUS:85083074032
SN - 1547-3287
VL - 29
SP - 440
EP - 451
JO - Stem Cells and Development
JF - Stem Cells and Development
IS - 7
ER -