Well, these interesting data seem to hold promise… at least in a rat model. Let’s see how things continue to translate.
JIRO KATO, HIDEKI KAMIYA, TATSUHITO HIMENO, TAIGA SHIBATA, TETSUJI OKAWA, MASAKI KONDO, ATSUSHI FUJIYA, YUSUKE SEINO, SHIN TSUNEKAWA, YOJI HAMADA, KEIKO NARUSE, YUTAKA OISO, JIRO NAKAMURA, Nagoya, Japan, Nagakute, Japan
Abstract: Aim: This study was conducted to evaluate the therapeutic effects of mesenchymal stem cells (MSCs) transplantation on the delayed foot ulcer healing under the diabetic condition using STZ-diabetic rats.
Methods: 1) MSCs were isolated from bone marrow of 5-week old SD rats, and their characters were analyzed by FACS and RT-PCR. 2) Human keratinocytes (HKCs) were cultured in 6 mM (NG), 12 mM (HG) or 25 mM (HHG) glucose concentrations with or without MSC-conditioned media (MSC-CM) for 72 hrs. Cell viabilities were evaluated by MTS assay. The abilities of migration and cytokine production were evaluated by RT-PCR. 3) Diabetic foot ulcer model: diabetes was induced by intraperitoneal injection of STZ to 6-week old SD rats. After 8 weeks of diabetes, a full thickness 4mm diameter punch holes were created in the hind paw of normal (N) and diabetic rats (D). MSCs (1×106) labeled with PKH were injected around the wounds. Wounds were photographed every other day. Wound tissues were excised and histological evaluations were performed.
Results:1) MSCs were positive for CD29/ CD90 and negative for CD34/ CD45. mRNA expressions of VEGF, bFGF, NGF, EGF and KGF were detected. 2) HKC viabilities were significantly impaired by HG or HHG, which was improved by MSC-CM. mRNA expression of MMP-2, MMP-9, EGF and IGF-1 were decreased by HG or HHG. And MSC-CM restored these HG-induced deficits. 3) MSCs survived in dermal and subcutaneous tissues even 2 weeks after transplantation. The duration of wound healing was significantly prolonged in D (N: 15.8±2.5 days, D: 21.2±1.9), which was significantly ameliorated by MSC transplantation (D+MSC: 18.3±2.1).
Conclusion:These observations indicate that MSC transplantation would be useful for treatment of diabetic foot ulcer through improving impaired keratinocyte functions.