Transplante de células-tronco mesenquimais: revisão sistemática, meta-análise e aplicações clínicas

Abstract

Acute kidney injury (AKI) and chronic kidney disease (CKD) are diseases which affect the urinary tract characterized by the loss of renal function. Even having different characteristics, they can present in similar ways in moments of crisis. However, the therapy for AKI usually aims the complete renal regeneration, as well as the management of CKD looks for slowing down their progression and give quality of life to the patient. Mesenchymal stem cells (MSC) transplantation has spread over the years as a treatment for many diseases. In the urinary tract, studies involving animal models report anti-inflammatory, antiapoptotic, antifibrotic, antioxidant and angiogenic effects, slowing down the progression of CKD and accelerating the kidney regeneration in AKI situation. Although there are studies in dogs and cats involving the MSC therapy in the urinary tract affections, no systematic reviews with metaanalysis have been conducted until this moment. Thereby, this work reports the results of a meta-analysis regarding the effects of the MSC application in serum levels of creatinine in dogs and cats with AKI and CKD. The work followed the methodologic guidelines entitled “Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)”. The bibliographic search involved the following search mechanisms: PubMed, Embase, Cinahl, Cochrane, Scopus and Web of Science and used three sets of terms: stem cells, kidney injury, and the species involved in the research. Data were screened, selected, and extracted for a spreadsheet with characteristics about the studies. The degree of injures were classified according to their identification and the risk of bias was calculated by the system Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE). Data underwent a descriptive analysis. The results of each group were combined by the inverse variance method. The representation happened as a forest plot. The heterogeneity was evaluated by the I 2 test. For the mean of creatinine, a meta-analysis was performed according to the study group and number of transplants, and separately for the control and treatment groups according to the kind of injury, dose, application route, and moment. We found, 4742 articles. Of these, 40 were selected for eligibility evaluation, 16 of which were sent to qualitative analysis and nine to the quantitative. The obtained results denote a better outcome in dogs and cats treated with mesenchymal stem cells over those which received placebo. A statistical difference could be observed both in combined analysis and in the subgroups division, when stratifications regarding the kind of injury, route of administration, dose, and measurement moment. However, a high heterogeneity was found, which indicates considerable variation in the results between the studies. The reasons can be due to differences in protocols of treatment, patient characteristics, or in the methodological quality. The great variation between the studies suggest caution to interpret the results and does not allow a definitive conclusion. In addition, this work presents two articles accepted for publication which involve results regarding the bone marrow mononuclear cells transplantation in two dogs, one with immune mediated thrombocytopenia and a second with chronic hepatopathy.