TY - JOUR
T1 - Translational application of human keratinocyte-fibroblast cell sheets for accelerated wound healing in a clinically relevant type 2 diabetic rat model
AU - Benchaprathanphorn, Kanokaon
AU - Muangman, Pornprom
AU - Chinaroonchai, Kusuma
AU - Namviriyachote, Nantaporn
AU - Ampawong, Sumate
AU - Angkhasirisap, Wannee
AU - Kengkoom, Kanchana
AU - Viravaidya-Pasuwat, Kwanchanok
N1 - Publisher Copyright:
© 2024 International Society for Cell & Gene Therapy
PY - 2024/4
Y1 - 2024/4
N2 - Background aims: Despite advancements in wound care, wound healing remains a challenge, especially in individuals with type 2 diabetes. Cell sheet technology has emerged as an efficient and promising therapy for tissue regeneration and wound repair. Among these, bilayered human keratinocyte-fibroblast cell sheets constructed using temperature-responsive culture surfaces have been shown to mimic a normal tissue-like structure and secrete essential cytokines and growth factors that regulate the wound healing process. Methods: This study aimed to evaluate the safety and therapeutic potential of human skin cell sheets to treat full-thickness skin defects in a rat model of type 2 diabetes. Results: Our findings demonstrate that diabetic wounds transplanted with bilayered cell sheets resulted in accelerated re-epithelialization, increased angiogenesis, enhanced macrophage polarization and regeneration of tissue that closely resembled healthy skin. In contrast, the control group that did not receive cell sheet transplantation presented characteristic symptoms of impaired and delayed wound healing associated with type 2 diabetes. Conclusions: The secretory cytokines and the upregulation of Nrf2 expression in response to cell sheet transplantation are believed to have played a key role in the improved wound healing observed in diabetic rats. Our study suggests that human keratinocyte-fibroblast cell sheets hold great potential as a therapeutic alternative for diabetic ulcers.
AB - Background aims: Despite advancements in wound care, wound healing remains a challenge, especially in individuals with type 2 diabetes. Cell sheet technology has emerged as an efficient and promising therapy for tissue regeneration and wound repair. Among these, bilayered human keratinocyte-fibroblast cell sheets constructed using temperature-responsive culture surfaces have been shown to mimic a normal tissue-like structure and secrete essential cytokines and growth factors that regulate the wound healing process. Methods: This study aimed to evaluate the safety and therapeutic potential of human skin cell sheets to treat full-thickness skin defects in a rat model of type 2 diabetes. Results: Our findings demonstrate that diabetic wounds transplanted with bilayered cell sheets resulted in accelerated re-epithelialization, increased angiogenesis, enhanced macrophage polarization and regeneration of tissue that closely resembled healthy skin. In contrast, the control group that did not receive cell sheet transplantation presented characteristic symptoms of impaired and delayed wound healing associated with type 2 diabetes. Conclusions: The secretory cytokines and the upregulation of Nrf2 expression in response to cell sheet transplantation are believed to have played a key role in the improved wound healing observed in diabetic rats. Our study suggests that human keratinocyte-fibroblast cell sheets hold great potential as a therapeutic alternative for diabetic ulcers.
KW - Nrf2
KW - cell sheet engineering
KW - skin cells
KW - type 2 diabetes
KW - wound healing
UR - http://www.scopus.com/inward/record.url?scp=85187508893&partnerID=8YFLogxK
U2 - 10.1016/j.jcyt.2024.01.003
DO - 10.1016/j.jcyt.2024.01.003
M3 - Article
C2 - 38363247
AN - SCOPUS:85187508893
SN - 1465-3249
VL - 26
SP - 360
EP - 371
JO - Cytotherapy
JF - Cytotherapy
IS - 4
ER -