title: Localization of human mesenchymal stem cells from umbilical cord blood and their role in repair of diabetic foot ulcers in rats.
abstract: The aim of this study is to explore the localization of human mesenchymal stem cells from umbilical cord matrix (hMSCs-UC) and the role of these cells in the repair of foot ulcerate tissue in diabetic foot ulcers in rats. A diabetic rat model was established by administering Streptozotocin. Diabetic foot ulceration was defined as non-healing or delayed-healing of empyrosis on the dorsal hind foot after 14 weeks. hMSCs-UC were delivered through the left femoral artery. We evaluated the localization of hMSCs-UC and their role in tissue repair in diabetic foot ulcers by histological analysis, PCR, and immunohistochemical staining. A model for diabetes was established in 54 out of 60 rats (90% success rate) and 27 of these rats were treated with hMSCs-UC. The area of ulceration was significantly and progressively reduced at 7 and 14 days following treatment with hMSCs-UC. This gross observation was strongly supported by the histological changes, including newly developed blood vessels and proliferation of inflammatory cells at 3 days post-treatment, significant increase in granulation tissue at 7 days post-treatment and squamous epithelium or stratified squamous epithelium at 14 days post-treatment. Importantly, human leukocyte antigen type-I (HLA-1) was confirmed in ulcerated tissue by RT-PCR. The expression of cytokeratin 19 was significantly increased in diabetic model rats, with no detectable change in cytokeratin 10. Additionally, both collagens I and III increased in model rats treated with hMSCs-UC, but the ratio of collagen I/III was less significant in treated rats compared with control rats. These results suggest that hMSCs-UC specifically localize to the target ulcerated tissue and may promote the epithelialization of ulcerated tissue by stimulating the release of cytokeratin 19 from keratinocytes and extracellular matrix formation.
authors.affiliation: 1. Department of endocrinology and Metabolism, the Fourth affiliated Hospital of Harbin Medical University.
authors.forename: Qing-Song
authors.initials: QS
authors.lastname: Zhao
authors.affiliation: 1. Department of endocrinology and Metabolism, the Fourth affiliated Hospital of Harbin Medical University.
authors.forename: Nan
authors.initials: N
authors.lastname: Xia
authors.affiliation: 1. Department of endocrinology and Metabolism, the Fourth affiliated Hospital of Harbin Medical University.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhao
authors.affiliation: 1. Department of endocrinology and Metabolism, the Fourth affiliated Hospital of Harbin Medical University.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: 1. Department of endocrinology and Metabolism, the Fourth affiliated Hospital of Harbin Medical University.
authors.forename: Chang-Long
authors.initials: CL
authors.lastname: Bi
authors.affiliation: 1. Department of endocrinology and Metabolism, the Fourth affiliated Hospital of Harbin Medical University.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: 2. Department of Pharmacology, Harbin Medical University; Harbin, China.
authors.forename: Guo-Fen
authors.initials: GF
authors.lastname: Qiao
authors.affiliation: 1. Department of endocrinology and Metabolism, the Fourth affiliated Hospital of Harbin Medical University.
authors.forename: Zhi-Feng
authors.initials: ZF
authors.lastname: Cheng
mesh_terms: D000818:Animals; D001483:Base Sequence; D003094:Collagen / Q000378:metabolism; D017931:DNA Primers; D017719:Diabetic Foot / Q000628:therapy*; D005312:Fetal Blood / Q000166:cytology*; D007633:Keratins / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013311:Streptozocin; D014470:Umbilical Cord / Q000166:cytology*
chemical_list: D017931:DNA Primers; D013311:Streptozocin; D007633:Keratins; D003094:Collagen
keywords: diabetic foot; human leukocyte antigen; human mesenchymal stem cell from umbilical cord matrix; tissue repair