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STESSUK, T. Cell therapy in chronic ulcers with implant of mesenchymal stem cells associated with platelet-rich plasma.2016. 142 p. Ph. D. thesis (Biotechnology) – Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, 2016. The economic and social burden related to treatment of chronic cutaneous ulcers are significant in Brazil and worldwide, as well as it is increasing the number of patients with systemic chronic diseases, i.e. diabetes mellitus, which favor the emergence and continuity of dermal-epidermal lesions. Cutaneous ulcers with difficult or lack of wound healing are subjected to several physiological and biochemical defects which contribute to the chronicity of the lesions and consequently the low effectiveness of conventional treatments and risk of amputation. In the context of the regenerative medicine for treatment of cutaneous chronic wounds, the clinical use of tissue bioengineering and cell therapy with adult stem cells has been considered as a new and promising therapeutic alternative. Regarding the physiological importance of the platelets factors during wound healing, the platelet-rich plasma (PRP) has been used for tissue regeneration and can act as a cellular scaffold. It is attributed to mesenchymal stem cells (MSC) immunomodulatory, anti-inflammatory, proliferative, anti-apoptotic and anti-fibrotic properties, which makes those cells extremely interesting to work in skin regenerative processes. In this context, the present study aims to evaluate the therapeutic efficiency, using adipose-derived mesenchymal stem cells (ADSC) associated with PRP obtained from autologous blood, for the treatment of cutaneous ulcers from diabetic patients. A preliminary in vitro component of the study provided the standardization of the production and gelation of PRP in accordance with cutaneous purpose. It has been further verified the positive and stimulatory influence of the PRP and conditioned medium from ADSC on the proliferation and migration of fibroblasts and keratinocytes, considered as crucial phases and key cell types during the skin healing process. Subsequently, the applied research was composed of six diabetic patients with chronic skin ulcers in the lower limbs, without significant healing for at least six months. Autologous PRP was produced and, after association with cultured ADSC, the final product was gelatinized in a shape of flexible membrane with dimensions of each lesion size. The photographic and clinical follow up showed the formation of granulation tissue starting from the first week after implantation. The total re-epithelialization occurred in 5 of the 10 lesions treated, and the average wound healing index was greater than 70% after 3 months of application. In this context, it can be concluded that ADSC therapy associated with PRP provides a reduction in ulcer area of chronic skin lesions in diabetic patients. First steps given in this work collaborate to the evolution of the cell therapy on the treatment of chronic cutaneous ulcers.

Terapia celular em úlceras crônicas com implante de células tronco mesenquimais associadas a plasma rico em plaquetas.