Morbid Cell Status and Donor Age Significantly Alter Mesenchymal Stem Cell Functionality and Reparability

Bone marrow (BM)-derived mesenchymal stem cells (MSCs) differentiate into specialized tissues, including cardiomyocytes, endothelial cells, and smooth muscle cells. Indeed, their demonstrated multi-lineage differentiation potential, lower immunoreactivity, paracrine activity, and availability from the autologous source make these cells superior candidates for myocardial repair and regeneration. Currently, BM-derived MSCs are being used in Phase-III pivotal trials in larger groups of patients to assess their myocardial reparability. However, these studies have reported less-than-optimal outcomes than preclinical and translational results. While reasoning out the modest clinical outcome, we hypothesized that autologous cells from elderly donors with comorbidities may be less efficacious than allogeneic cells from young, healthy donors due to chronological aging and disease-induced cellular stress and morbidity. This chapter primarily aims to provide an overview of the published data to highlight the factors responsible for the modest outcome observed in clinical settings, especially concerning the donors’ age and morbid health status.