TY - JOUR
T1 - Nanofiber-expanded human umbilical cord blood-derived CD34+ cell therapy accelerates murine cutaneous wound closure by attenuating pro-inflammatory factors and secreting IL-10
AU - Kanji, Suman
AU - Das, Manjusri
AU - Aggarwal, Reeva
AU - Lu, Jingwei
AU - Joseph, Matthew
AU - Basu, Sujit
AU - Pompili, Vincent J.
AU - Das, Hiranmoy
N1 - Funding Information:
This work was part of the PhD dissertation thesis of Suman Kanji. This work was supported in part by the National Institutes of Health grants, K01 AR054114 (NIAMS), SBIR R44 HL092706-01 (NHLBI) and R01 DK098045 (SB), Pelotonia IDEA Award , and The Ohio State University start-up fund. Nanofiber-coated plates were a kind gift from Hai-Quan Mao (John's Hopkins University, MD). Human primary skin fibrobalst cells were a kind gift from Heather M. Powell, The Ohio State University. The authors are thankful to Drs. Mukesh K. Jain (Case Western Reserve University) and Jack F. Bukowski (Brigham and Women's Hospital, Harvard Medical School) for their critical reading of the manuscript and thoughtful suggestions.
PY - 2014/1
Y1 - 2014/1
N2 - Nanofiber-expanded human umbilical cord blood-derived CD34. + cell therapy is under consideration for treating peripheral and cardiac ischemia. However, the therapeutic efficacy of nanofiber-expanded human umbilical cord blood-derived (NEHUCB) CD34. + cell therapy for wound healing and its mechanisms are yet to be established. Using an excision wound model in NOD/SCID mice, we show herein that NEHUCB-CD34. + cells home to the wound site and significantly accelerate the wound-healing process compared to vehicle-treated control. Histological analysis reveals that accelerated wound closure is associated with the re-epithelialization and increased angiogenesis. Additionally, NEHUCB-CD34. + cell-therapy decreases expression of pro-inflammatory cytokines, such as TNF-α, IL-1β, IL-6 and NOS2A in the wound bed, and concomitantly increases expression of IL-10 compared to vehicle-treated control. These findings were recapitulated in vitro using primary dermal fibroblasts and NEHUCB-CD34. + cells. Moreover, NEHUCB-CD34. + cells attenuate NF-κB activation and nuclear translocation in dermal fibroblasts through enhanced secretion of IL-10, which is known to bind to NF-κB and suppress transcriptional activity. Collectively, these data provide novel mechanistic evidence of NEHUCB-CD34. + cell-mediated accelerated wound healing.
AB - Nanofiber-expanded human umbilical cord blood-derived CD34. + cell therapy is under consideration for treating peripheral and cardiac ischemia. However, the therapeutic efficacy of nanofiber-expanded human umbilical cord blood-derived (NEHUCB) CD34. + cell therapy for wound healing and its mechanisms are yet to be established. Using an excision wound model in NOD/SCID mice, we show herein that NEHUCB-CD34. + cells home to the wound site and significantly accelerate the wound-healing process compared to vehicle-treated control. Histological analysis reveals that accelerated wound closure is associated with the re-epithelialization and increased angiogenesis. Additionally, NEHUCB-CD34. + cell-therapy decreases expression of pro-inflammatory cytokines, such as TNF-α, IL-1β, IL-6 and NOS2A in the wound bed, and concomitantly increases expression of IL-10 compared to vehicle-treated control. These findings were recapitulated in vitro using primary dermal fibroblasts and NEHUCB-CD34. + cells. Moreover, NEHUCB-CD34. + cells attenuate NF-κB activation and nuclear translocation in dermal fibroblasts through enhanced secretion of IL-10, which is known to bind to NF-κB and suppress transcriptional activity. Collectively, these data provide novel mechanistic evidence of NEHUCB-CD34. + cell-mediated accelerated wound healing.
UR - http://www.scopus.com/inward/record.url?scp=84890208547&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84890208547&partnerID=8YFLogxK
U2 - 10.1016/j.scr.2013.11.005
DO - 10.1016/j.scr.2013.11.005
M3 - Article
C2 - 24321844
AN - SCOPUS:84890208547
VL - 12
SP - 275
EP - 288
JO - Stem Cell Research
JF - Stem Cell Research
SN - 1873-5061
IS - 1
ER -