Machine learning reveals the rules governing the efficacy of mesenchymal stromal cells in septic preclinical models.

BACKGROUND: Mesenchymal Stromal Cells (MSCs) are the preferred candidates for therapeutics as they possess multi-directional differentiation potential, exhibit potent immunomodulatory activity, are anti-inflammatory, and can function like antimicrobials. These capabilities have therefore encouraged scientists to undertake numerous preclinical as well as a few clinical trials to access the translational potential of MSCs in disease therapeutics. In spite of these efforts, the efficacy of MSCs has not been consistent-as is reflected in the large variation in the values of outcome measures like survival rates. Survival rate is a resultant of complex cascading interactions that not only depends upon upstream experimental factors like dosage, time of infusion, type of transplant, etc.; but is also dictated, post-infusion, by intrinsic host specific attributes like inflammatory microniche including proinflammatory cytokines and alarmins released by the damaged host cells. These complex interdependencies make a researcher's task of designing MSC transfusion experiments challenging. METHODS: In order to identify the rules and associated attributes that influence the final outcome (survival rates) of MSC transfusion experiments, we decided to apply machine learning techniques on manually curated data collected from available literature. As sepsis is a multi-faceted condition that involves highly dysregulated immune response, inflammatory environment and microbial invasion, sepsis can be an efficient model to verify the therapeutic effects of MSCs. We therefore decided to implement rule-based classification models on data obtained from studies involving interventions of MSCs in sepsis preclinical models. RESULTS: The rules from the generated graph models indicated that survival rates, post-MSC-infusion, are influenced by factors like source, dosage, time of infusion, pre-Interleukin-6 (IL-6)/ Tumour Necrosis Factor- alpha (TNF-α levels, etc. CONCLUSION: This approach provides important information for optimization of MSCs based treatment strategies that may help the researchers design their experiments.

Fine Tuning Mesenchymal Stromal Cells - Code For Mitigating Kidney Diseases.

Kidney Disease (KD), has a high global prevalence and accounts for one of the most prominent causes of morbidity and mortality in the twenty-first century. Despite the advances in our understanding of its pathophysiology, the only available therapy options are dialysis and kidney transplantation. Mesenchymal stem cells (MSCs) have proven to be a viable choice for KD therapy due to their antiapoptotic, immunomodulatory, antioxidative, and pro-angiogenic activities. However, the low engraftment, low survival rate, diminished paracrine ability, and delayed delivery of MSCs are the major causes of the low clinical efficacy. A number of preconditioning regimens are being tested to increase the therapeutic capabilities of MSCs. In this review, we highlight the various strategies to prime MSCs and their protective effects in kidney diseases.