Bioimaging assessment and effect of skin wound healing using bone-marrow-derived mesenchymal stromal cells with the artificial dermis in diabetic rats

Abstract

We investigate the relationship between the fate and healing effect of transplanted mesenchymal stromal cells (MSCs) in a rat diabetic skin wound model. Rats are treated with streptozotocin to induce diabetic conditions. A full-thickness skin defect is surgically made on the head of diabetic rats, and covered with an artificial dermis impregnated with either bone marrow cells (BMCs) or bone-marrow-derived MSCs from firefly luciferase (luc) transgenic (Tg) rats. Wound healing is evaluated using planimetry and immunohistochemistry, and the fate of transplanted MSCs is determined using in-vivo luminescent imaging. The diabetic wound treated with MSCs-impregnated artificial dermis is significantly smaller than that treated with artificial dermis alone at 1 week postoperation. Photons of luc+ MSCs are detected at the transplanted site during healing (3 weeks), whereas those of luc+ MSCs are depleted only after 1 week postimplantation. Immunohistochemistry at the healing site treated with MSCs demonstrates that CD31+ vessels increase with expression of vascular endothelial growth factor, suggesting that MSCs accelerate angiogenesis. These findings suggest that transplanted MSCs could be retained at wound sites during the healing process in a diabetic rat model, and subsequently promote wound healing through angiogenesis.

Role of the autologous mesenchymal stem cells compared with platelet rich plasma on cicatrization of cutaneous wounds in diabetic mice

“…The persistent fasting hyperglycemia associated to the manifestation of emaciation and polidipsia, proves the induction of DM, which experimental model has already been successfully described in rats, mice and dogs (Volpato et al 2006, Inoue et al 2008, Kwon et al 2008, Buschard 2011, Maharlooei et al 2011. The persistance of hyperglycemia, during the insulin treatment, observed in the present study, was also described in recent researches (Delfino et al 2002, Spadella et al 2005.…”

“…The characteristic morphology and the molecular level by flow cytometry of MSC cultivated in this study was the same described by other studies for identifying murine MSC (Badillo et al 2007, Falanga et al 2007, Inoue et al 2008, Kwon et al 2008, Mehta et al 2010, Jiang et al 2011, Kim et al 2011.…”

“…One of the main anti-inflammatory soluble factors produced by the MSC is the indoleamine 2,3-dioxygenase (IDO) (Kim et al 2011, Inoue et al 2008. It is possible that the used MSC in this study have contributed positively in the reduction of the inflammatory phase of cicatrization in mice of the GSC by means of the IDO secretion.…”

“…Furthermore, the hyperglycemia could have been the responsible for the higher values found for the LA variables between the mice in the witness and polyurethane groups (Table 1), since it is incriminated as the main responsible for the chronicity of cutaneous lesions in diabetic humans and rodents treated with STZ (Volpato et al 2006, Inoue et al 2008, Kwon et al 2008, Buschard 2011, Maharlooei et al 2011.…”

Therapeutic Potential of Canine Bone Marrow Derived Mesenchymal Stem Cells and its Conditioned Media in Diabetic Rat Wound Healing

“…Stem cell application is a new hope to treat difficult to heal wounds or chronic wounds [8] as diabetic wounds. Transplanted BMSCs could be retained at the wound sites during the healing process and subsequently promote wound healing through angiogenesis [9]. MSC conditioned (MSC-CM) media having a variety of growth factors; cytokines etc.…”