Mesenchymal stem cells ameliorate impaired wound healing through enhancing keratinocyte functions in diabetic foot ulcerations on the plantar skin of rats

Jiro Kato, Hideki Kamiya, Tatsuhito Himeno, Taiga Shibata, Masaki Kondo, Tetsuji Okawa, Atsushi Fujiya, Ayako Fukami, Eita Uenishi, Yusuke Seino, Shin Tsunekawa, Yoji Hamada, Keiko Naruse, Yutaka Oiso, Jiro Nakamura

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

Aims/hypothesis Although the initial healing stage involves a re-epithelialization in humans, diabetic foot ulceration (DFU) has been investigated using rodent models with wounds on the thigh skin, in which a wound contraction is initiated. In this study, we established a rodent model of DFU on the plantar skin and evaluated the therapeutic efficacy of bone-marrow-derived mesenchymal stem cells (BM-MSCs) in this model. Methods The wounds made on the hind paws or thighs of streptozotocin induced diabetic or control rats were treated with BM-MSCs. Expression levels of phosphorylated focal adhesion kinase (pFAK), matrix metaroprotease (MMP)-2, EGF, and IGF-1, were evaluated in human keratinocytes, which were cultured in conditioned media of BM-MSCs (MSC-CM) with high glucose levels. Results Re-epithelialization initiated the healing process on the plantar, but not on the thigh, skin. The therapy utilizing BM-MSCs ameliorated the delayed healing in diabetic rats. In the keratinocytes cultured with MSC-CM, the decreased pFAK levels in the high glucose condition were restored, and the MMP2, EGF, and IGF-1 levels increased. Conclusions/interpretation Our study established a novel rat DFU model. The impaired healing process in diabetic rats was ameliorated by transplantation of BM-MSCs. This amelioration might be accounted for by the modification of keratinocyte functions.

Original languageEnglish
Pages (from-to)588-595
Number of pages8
JournalJournal of Diabetes and its Complications
Volume28
Issue number5
DOIs
Publication statusPublished - 01-01-2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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