Clinical parameters of leukogram and weight were analyzed in animal models before and after seven days of 5-FU infusions. A comparison of leukograms before and after 5-FU administrations was analyzed. The results showed a significant difference (p = 0,004), confirming immunosuppression. There was a decrease in the weight of the animals after 7 days of 5-FU infusions (p = 0.02). After immunosuppression occurred, oral mucositis (OM) ulcerative lesions were observed. Two of the animals were selected to receive PLGA dressings. Then, electrospun PLGA membranes, with or without autologous cells, were applied to the ulcerative lesions, aiming to accelerate the regeneration process. Although this therapeutic innovation for OM lesions was still not tested in the bioengineering area, morphological analysis presented promising results. Lesions covered by cell-free PLGA, exhibited areas of inflammation persistence and angiogenesis. The cell-seeded cell-seeded PLGA membrane exhibited complete reepithelialization after 6 days, with minor inflammatory infiltrate. Interestingly, the present work showed preclinical parameters of cachexia induced by chemotherapy for cancer treatment. Moreover, it showed an innovative approach by applying dressings consisting of electrospun PLGA with the addition of autologous mesenchymal cells for OM ulcerative lesions. This promising innovation will pave the way for future applications in oral mucosa lesions.