Diabetes 2013 July-8

 

The regenerative potential of fibroblasts in a new diabetes-induced delayed humanised wound healing model.

Exp Dermatol. 2013 Mar;22(3):195-201.

Martínez-Santamaría L, Conti CJ, Llames S, García E, Retamosa L, Holguín A, Illera N, Duarte B, Camblor L, Llaneza JM, Jorcano JL, Larcher F, Meana Á, Escámez MJ, Del Río M.

Department of Bioengineering, Carlos III University, Madrid, Spain.

Abstract

Cutaneous diabetic wounds greatly affect the quality of life of patients, causing a substantial economic impact on the healthcare system. The limited clinical success of conventional treatments is mainly attributed to the lack of knowledge of the pathogenic mechanisms related to chronic ulceration. Therefore, management of diabetic ulcers remains a challenging clinical issue. Within this context, reliable animal models that recapitulate situations of impaired wound healing have become essential. In this study, we established a new in vivo humanised model of delayed wound healing in a diabetic context that reproduces the main features of the human disease. Diabetes was induced by multiple low doses of streptozotocin in bioengineered human-skin-engrafted immunodeficient mice. The significant delay in wound closure exhibited in diabetic wounds was mainly attributed to alterations in the granulation tissue formation and resolution, involving defects in wound bed maturation, vascularisation, inflammatory response and collagen deposition. In the new model, a cell-based wound therapy consisting of the application of plasma-derived fibrin dermal scaffolds containing fibroblasts consistently improved the healing response by triggering granulation tissue maturation and further providing a suitable matrix for migrating keratinocytes during wound re-epithelialisation. The present preclinical wound healing model was able to shed light on the biological processes responsible for the improvement achieved, and these findings can be extended for designing new therapeutic approaches with clinical relevance. © 2013 John Wiley & Sons A/S.

PMID: 23489422

Supplementary figure:

MªJosé Escámez Toledano

Treatment of diabetic wounds with bioengineered dermal equivalents in the skin-humanized mouse model. (A) The skin-umanized mouse model is based on the permanent engraftment of ex vivo bioengineered human skin onto the back of immunodeficient mice. The bioengineered human skin equivalent consists of a fibrin-based matrix containing live fibroblasts as a dermal component and keratinocytes as the epidermal component. Cells and fibrin are obtained respectively from skin biopsies and plasma of healthy donors. (B) Schematic representation of the grafting protocol and the induction of experimental diabetes by streptozotocin (STZ) in the skin-humanized mice. Diabetic skinhumanized mice underwent full-thickness cutaneous wounding and were treated with bioengineered dermal equivalents containing human fibroblasts.

 

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