The effects of allogenic stem cells in a murine model of hind limb diabetic ischemic tissue

Abstract

BackgroundDiabetes is one of the major risk factors for peripheral arterial disease. In patients in whom surgery cannot be performed, cell therapy may be an alternative treatment. Since time is crucial for these patients, we propose the use of allogenic mesenchymal cells.MethodsWe obtained mesenchymal cells derived from the fat tissue of a healthy Sprague-Dawley rat. Previous diabetic induction with streptozotocin in 40 male Sprague-Dawley rats, ligation plus left iliac and femoral artery sections were performed as a previously described model of ischemia. After 10 days of follow-up, macroscopic and histo-pathological analysis was performed to evaluate angiogenic and inflammatory parameters in the repair of the injured limb. All samples were evaluated by the same blind researcher. Statistical analysis was performed using the SPSS v.11.5 program (P < 0.05).ResultsSeventy percent of the rats treated with streptozotocin met the criteria for diabetes. Macroscopically, cell-treated rats presented better general and lower ischemic clinical status, and histologically, a better trend towards angiogenesis, greater infiltration of type 2 macrophages and a shortening of the inflammatory process. However, only the inflammatory variables were statistically significant. No immunological reaction was observed with the use of allogeneic cells.DiscussionThe application of allogeneic ASCs in a hind limb ischemic model in diabetic animals shows no rejection reactions and a reduction in inflammatory parameters in favor of better repair of damaged tissue. These results are consistent with other lines of research in allogeneic cell therapy. This approach might be a safe, effective treatment option that makes it feasible to avoid the time involved in the process of isolation, expansion and production of the use of autologous cells.

Analysis of Biological Properties of Human Adult Mesenchymal Stem Cells and Their Effect on Mouse Hind Limb Ischemia

“…In accordance with other reported preclinical studies [2, 19, 59, 63], in our experiments, AMSC injection was followed by an increase in neovascularization. We have been able to assess the significant increase as early as 1 week after treatment.…”

Secreted Factors from Stem Cells of Human Exfoliated Deciduous Teeth Directly Activate Endothelial Cells to Promote All Processes of Angiogenesis

“…The TACT (Therapeutic Angiogenesis using Cell Transplantation) study first demonstrated the efficacy and safety of autologous BM-MNC transplantation for critical limb ischemia (CLI) [49], but subsequent meta-analysis of 10 randomized controlled trials showed no significant differences in major amputation rates, survival, or amputation-free survival between patients treated with BM-MNCs or placebos [50]. In recent clinical studies, transplantation of MSCs has gained interest and is the most widely examined as a new strategy for vascular diseases in both humans and animal models [51]. According to ClinicalTrials.gov, to date (March 2020), 23 clinical trials were registered to investigate therapeutic effects of MSC transplantation on CLI.…”

Cost-Effective, Safe, and Personalized Cell Therapy for Critical Limb Ischemia in Type 2 Diabetes Mellitus

“…There were no differences among functional parameters in patients undergoing intramuscular vs. intraarterial cell supply. Preclinical (66) and clinical (67) data from our group substantiate these remarks; nevertheless, our humble experience indicates that the route of administration depends on the type and the dose of cell to be administered. Deciphering how stem cells manage the countless signals required for revascularization will improve CLI recovery, Qadura et al (31) proposed a combination delivery of multiple cell types within supportive bioengineered matrices as a new therapeutic strategy to target CLI.…”

“…Regarding the use of MSCs as a cell-based therapy for CLI, recent data suggest that the therapeutic effects of these cells in ischemic pathologies are due to the secretion of angiogenic molecules to bioactive levels and their ability to restore the microenvironment of the damaged area (70). In preclinical studies, the administration of autologous, allogeneic, and xenogeneic MSCs derived from various sources such as bone marrow, umbilical cord blood, fetal membrane and adipose tissue have been shown to be beneficial in rat and mouse models with lower limb ischemia (66). Subsequently, several phase I/IIa clinical trials have been assayed in a limited number of patients to demonstrate the safety and feasibility of MSCs obtained from different sources (71–75).…”