Treatment with bone marrow‐derived stromal cells accelerates wound healing in diabetic rats

Abstract

Bone marrow stem cells participate in tissue repair processes and may have a role in wound healing. Diabetes is characterised by delayed and poor wound healing. We investigated the potential of bone marrow-derived mesenchymal stromal cells (BMSCs) to promote healing of fascial wounds in diabetic rats. After manifestation of streptozotocin (STZ)-induced diabetic state for 5 weeks in male adult Sprague-Dawley rats, healing of fascial wounds was severely compromised. Compromised wound healing in diabetic rats was characterised by excessive polymorphonuclear cell infiltration, lack of granulation tissue formation, deficit of collagen and growth factor [transforming growth factor (TGF-beta), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor PDGF-BB and keratinocyte growth factor (KGF)] expression in the wound tissue and significant decrease in biomechanical strength of wounds. Treatment with BMSC systemically or locally at the wound site improved the wound-breaking strength (WBS) of fascial wounds. The improvement in WBS was associated with an immediate and significant increase in collagen levels (types I-V) in the wound bed. In addition, treatment with BMSCs increased the expression of growth factors critical to proper repair and regeneration of the damaged tissue moderately (TGF-beta, KGF) to markedly (EGF, VEGF, PDGF-BB). These data suggest that cell therapy with BMSCs has the potential to augment healing of the diabetic wounds.

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

“…Furthermore, in our experiment, quality of wound healing (in terms of epithelization, neovascularization and collagen deposition characteristics) on 28 th day post surgery was found to be better in stem cell and CM groups than control groups. Kwon et al [5] reported that allogenic stem cell treatment resulted in thicker, denser and well arranged collagen deposition in diabetic wound healing in rabbits though, did not correlated it with conditioned media (no study available regarding treatment with stem cell conditioned media). No significant difference in stem cell treatment and CM treatment may be due to treatment with these two in small intervals (about 7 day interval).…”

“…Group I, II and III were non-diabetic while group IV, V and VI were diabetic with six animals in each group (Table 1). Group II and V received stem cells (2x10 5 per dose) in culture media and group III and VI received conditioned media (1ml dose) while group I and IV were kept as respective controls given only stem cell culture media (1 ml dose). Stem cells and its conditioned media were injected at the periphery of wounds.…”

“…The sequence of cellular and molecular events, are disturbed in diabetes resulting impaired wound healing. MSCs improve healing of diabetic wounds in rats and significantly increase collagen levels in diabetic wounds and wound breaking strength [5] but the mechanisms of impaired wound healing in diabetes are not completely understood. The function of neutrophils and macrophages, including cell adherence, chemotaxis, phagocytosis, cytokine production and secretion are inhibited in diabetes [6,7].…”

Effect of diabetic osteoblasts on osteogenic differentiation of human umbilical cord mesenchymal stem cells

“…Recently, cell therapy with bone marrow mesenchymal stem cells (MSCs) has been trialed to treat chronic wounds in diabetics [5][6][7] . The main functional characteristics of MSCs are their immunomodulatory ability, capacity for self-renewal, and differentiation into mesodermal tissues, such as bone cells 8 .…”

Early Experiences with Stem Cells in Treating Chronic Wounds

“…In addition, direct injection of cultured BMMSC into the wound area in normal diabetic mice promoted wound healing through release of proangiogenic factors upon differentiation (39). ; In streptozocin (STX)-induced diabetic rats, BMMSC double-system injections through the tail vein and local injection at the wound site augmented growth factors such as EGF, VEGF, PDGF-BB markedly and TGF-β and KGF moderately (40). BMMSC induce potent differentiation and proliferation under low oxygen tension with cell morphological and cell cycle changes and differentiation capacity towards bone and fat (42).…”