TY - JOUR
T1 - Mesenchymal stem cells ameliorate impaired wound healing through enhancing keratinocyte functions in diabetic foot ulcerations on the plantar skin of rats
AU - Kato, Jiro
AU - Kamiya, Hideki
AU - Himeno, Tatsuhito
AU - Shibata, Taiga
AU - Kondo, Masaki
AU - Okawa, Tetsuji
AU - Fujiya, Atsushi
AU - Fukami, Ayako
AU - Uenishi, Eita
AU - Seino, Yusuke
AU - Tsunekawa, Shin
AU - Hamada, Yoji
AU - Naruse, Keiko
AU - Oiso, Yutaka
AU - Nakamura, Jiro
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.jdiacomp.2014.05.003
DO - 10.1016/j.jdiacomp.2014.05.003
M3 - Article
C2 - 25027388
AN - SCOPUS:84906794546
VL - 28
SP - 588
EP - 595
JO - Journal of Diabetes and its Complications
JF - Journal of Diabetes and its Complications
SN - 1056-8727
IS - 5
ER -