Proposta científica teórica para o isolamento, caracterização e aplicação de células-tronco mesenquimais derivadas da urina (USCs) na terapia regenerativa da doença renal crônica felina

Abstract

Chronic kidney disease is among the most prevalent conditions in elderly domestic cats and still lacks a therapeutic approach capable of promoting repair of the renal parenchyma, which has driven the investigation of strategies based on mesenchymal stem cells. In this context, urine-derived stem cells (USCs) emerge as a source of interest that remains poorly explored in feline medicine. The present study aimed to critically analyze whether current scientific evidence supports USCs as a theoretically more suitable, feasible and biologically coherent source than traditional sources for the isolation, characterization and future therapeutic application in this disease, and to propose, based on this analysis, an integrated laboratory protocol. A theoretical-propositional approach was adopted, conducted through a review of the contemporary scientific literature published between 2015 and 2026, retrieved from national and international databases, with previously defined inclusion and exclusion criteria and data extraction into a comparative thematic matrix. The analysis evidenced the shift from the paradigm based on cellular differentiation towards the predominance of biological modulation mediated by the secretome and by extracellular vesicles, and demonstrated that tissue origin conditions the repertoire of released mediators. Limitations of conventional sources were identified, such as bone marrow, adipose tissue and perinatal tissues, particularly regarding the invasiveness of collection, biological heterogeneity and difficulties in standardization. USCs stood out for their minimally invasive collection, the possibility of serial sampling and cryopreservation, and their potential biological affinity with the nephrourological system, associated with the elevated expression of α-Klotho, a protein whose reduction accompanies the progression of nephropathy. The main mechanisms proposed for their action in chronic kidney disease were discussed, including immunomodulation, paracrine activity, tubular preservation, microvascular protection and attenuation of renal fibrosis. Furthermore, the absence of studies that have isolated or characterised USCs in the feline species was verified. From the comparison of the divergent parameters described in the literature, an operational protocol was developed, classifying each technical decision according to the degree of available support, distinguishing what can be extrapolated from human protocols, what required adaptation to the species, and what remains dependent on experimental validation. It was concluded that there is sufficient biological plausibility to justify the experimental investigation of USCs in feline chronic kidney disease, although current evidence does not allow efficacy or safety to be asserted, which is why the proposal is presented as a scientifically grounded hypothesis rather than as a validated therapy.