Localization of human mesenchymal stem cells from umbilical cord blood and their role in repair of diabetic foot ulcers in rats

• Published in: International journal of biological sciences 2013-12, Vol.10 (1), p.80-89
• Main Authors: Zhao, Qing-Song, Xia, Nan, Zhao, Nan, Li, Ming, Bi, Chang-Long, Zhu, Qing, Qiao, Guo-Fen, Cheng, Zhi-Feng
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Collagen - metabolism; Diabetic Foot - therapy; DNA Primers; Fetal Blood - cytology; Keratins - metabolism; Male; Mesenchymal Stromal Cells - cytology; Rats; Rats, Sprague-Dawley; Research Paper; Reverse Transcriptase Polymerase Chain Reaction; Streptozocin; Umbilical Cord - cytology
• ISSN: 1449-2288; 1449-2288
• DOI: 10.7150/ijbs.7237

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.