title: Nanofiber-expanded human umbilical cord blood-derived CD34+ cell therapy accelerates murine cutaneous wound closure by attenuating pro-inflammatory factors and secreting IL-10.
abstract: 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.
authors: Stem Cell Research Laboratory, Cardiovascular Medicine, Davis Heart and Lung Research Institute, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA.
authors: Suman
authors: S
authors: Kanji
authors: Stem Cell Research Laboratory, Cardiovascular Medicine, Davis Heart and Lung Research Institute, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA.
authors: Manjusri
authors: M
authors: Das
authors: Stem Cell Research Laboratory, Cardiovascular Medicine, Davis Heart and Lung Research Institute, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA.
authors: Reeva
authors: R
authors: Aggarwal
authors: Stem Cell Research Laboratory, Cardiovascular Medicine, Davis Heart and Lung Research Institute, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA.
authors: Jingwei
authors: J
authors: Lu
authors: Stem Cell Research Laboratory, Cardiovascular Medicine, Davis Heart and Lung Research Institute, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA.
authors: Matthew
authors: M
authors: Joseph
authors: Department of Pathology, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA.
authors: Sujit
authors: S
authors: Basu
authors: Stem Cell Research Laboratory, Cardiovascular Medicine, Davis Heart and Lung Research Institute, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA.
authors: Vincent J
authors: VJ
authors: Pompili
authors: Stem Cell Research Laboratory, Cardiovascular Medicine, Davis Heart and Lung Research Institute, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA. Electronic address: hiranmoy.das@osumc.edu.
authors: Hiranmoy
authors: H
authors: Das
mesh_terms: D000818:Animals; D064987:Cell- and Tissue-Based Therapy; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D057139:Nanofibers / Q000737:chemistry; D011485:Protein Binding; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D012871:Skin Diseases / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology*; D014157:Transcription Factors / Q000378:metabolism; D014945:Wound Healing
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D011994:Recombinant Proteins; D014157:Transcription Factors; D016753:Interleukin-10
keywords: 4′,6-diamidino-2-phenyl indole; DAPI; ELISA; GFP; H & E; IL-10; IL-1β; IL-6; NEHUCB; NF-κB; NOD/SCID; PBS; RT-PCR; SFEM; TNF-α; WB; enzyme-linked immunosorbent assay; green fluorescent protein; hematoxylin and eosin; iNOS/NOS2A; inducible nitric oxide synthase; interleukin-10; interleukin-1β; interleukin-6; nanofiber-expanded human umbilical cord blood-derived; non-obese diabetes severe combined immune deficiency; nuclear factor kappa-light-chain-enhancer of activated B cells; phosphate-buffered saline; real-time polymerase chain reaction; serum-free expansion medium; tumor necrosis factor-α; vWF; von Willebrand factor; western blot