Abstract
Diabetes mellitus is associated with neural and micro- and macrovascular complications. Therapeutic options for these complications are limited and the delivery of mesenchymal stem cells into lesions have been reported to improve the healing process. In this work, the effects of the administration of a lineage of human bone marrow mesenchymal stem cells immortalized by the expression of telomerase (hBMSC-TERT) as a potential therapeutic tool for wound healing in diabetic rats were investigated. This is the first description of the use of these cells in diabetic wounds. Dorsal cutaneous lesions were made in streptozotocin-induced diabetic rats and hBMSC-TERT were subcutaneously administered around the lesions. The healing process was evaluated macroscopically, histologically, and by birefringence analysis. Diabetic wounded rats infused with hBMSC-TERT (DM-TERT group) and the non-diabetic wounded rats not infused with hBMSC-TERT (CW group) had very similar patterns of fibroblastic response and collagen proliferation indicating improvement of wound healing. The result obtained by birefringence analysis was in accordance with that obtained by the histological analysis. The results indicated that local administration of hBMSC-TERT in diabetic wounds improved the wound healing process and may become a therapeutic option for wounds in individuals with diabetes.
Highlights
Chronic hyperglycemia due to diabetes mellitus (DM) causes neural and micro- and macro-vascular complications
More than 100 abnormalities have been described in the diabetic wound healing process and their combined actions result in the disruption of the finely ordered sequence of events leading to the reconstitution of cutaneous integrity
For the semi-quantitative analyses, a qualified pathologist used the following scale proposed by De Mayo et al [26] to estimate the degree of leukocyte infiltration, fibroblastic response, and collagen proliferation: 0) absent; 1) mild inflammatory response or proliferation findings (o10% of the area covered by inflammatory cells, fibroblastic response, or collagen proliferation); 2) moderate inflammatory response or proliferation findings (10 to 50% of the area covered by inflammatory cells, fibroblastic response, or collagen proliferation); and 3) severe inflammatory response
Summary
Chronic hyperglycemia due to diabetes mellitus (DM) causes neural and micro- and macro-vascular complications. More than 100 abnormalities have been described in the diabetic wound healing process and their combined actions result in the disruption of the finely ordered sequence of events leading to the reconstitution of cutaneous integrity. Such changes involve angiogenic responses [3], quantity of granulation tissue, keratinocytes, fibroblast, and macrophage activation, migration and proliferation [3,4], accumulation of extracellular matrix components and their remodeling [5,6], and the complex interaction between the wound and the organism mediated by cytokines, chemokines, and other signaling proteins [7,8].
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