Tudy. Information Availability Statement: The data presented within this study are available from the corresponding authors upon affordable request. Conflicts of Interest: The authors declare no conflict of interest.J. Pers. Med. 2021, 11,8 ofJournal ofPersonalized MedicineReviewCell and Cell-Free Therapies to Counteract Human Premature and Physiological Aging: MSCs Come to Light2-Thiouracil Data Sheet arantza Infante and Clara I. Rodr uez Stem Cells and Cell Therapy Laboratory, Biocruces Bizkaia Health Research Institute, Cruces University Hospital, 48903 Barakaldo, Spain; [email protected] Correspondence: [email protected]: Infante, A.; Rodr uez, C.I. Cell and Cell-Free Therapies to Counteract Human Premature and Physiological Aging: MSCs Come to Light. J. Pers. Med. 2021, 11, 1043. ten.3390/ jpm11101043 Academic Editor: Drenka CGS 21680 Autophagy Trivanovic Received: 3 September 2021 Accepted: 14 October 2021 Published: 18 OctoberAbstract: The progressive loss from the regenerative potential of tissues is among the most apparent consequences of aging, driven by altered intercellular communication, cell senescence and nichespecific stem cell exhaustion, amongst other drivers. Mesenchymal tissues, including bone, cartilage and fat, which originate from mesenchymal stem cell (MSC) differentiation, are in particular impacted by aging. Senescent MSCs show restricted proliferative capacity and impairment in key defining features: their multipotent differentiation and secretory abilities, major to diminished function and deleterious consequences for tissue homeostasis. Inside the past few years, several interventions to enhance human healthspan by counteracting the cellular and molecular consequences of aging have moved closer to the clinic. Taking into account the MSC exhaustion occurring in aging, advanced therapies determined by the potential use of young allogeneic MSCs and derivatives, such as extracellular vesicles (EVs), are gaining consideration. According to encouraging pre-clinical and clinical information, this overview assesses the robust prospective of MSC-based (cell and cell-free) therapies to counteract age-related consequences in both physiological and premature aging scenarios. We also discuss the mechanisms of action of these therapies plus the possibility of enhancing their clinical potential by exposing MSCs to niche-relevant signals. Key phrases: MSCs; cell therapies; cell-free therapies; extracellular vesicles; physiological aging; premature aging; paracrine mechanism; inflammation; stem cell exhaustion1. Introduction Aging, an inexorable consequence of life, might be defined by a time-dependent loss of cellular and molecular homeostasis, top to impaired function of tissues and organs which might be unable to activate appropriate compensatory mechanisms to restore the lost functionality [1]. Affecting practically all tissues, organs and systems in an organism, aging itself will be the stronger risk for the improvement of age-related pathologies [2]. The consequences of aging are specifically visible in tissues of mesenchymal origin, for example connective tissues (bone, cartilage and fat) plus the cardiovascular method. Hence, musculoskeletal issues, which include osteoporosis and osteoarthritis and body fat redistribution and loss, along with cardiovascular pathologies, are among the most prevalent pathological features shared by the elderly, instigating chronic disability, and in consequence, long-term healthcare needs [3]. Mesenchymal stem cells (MSCs) are adult stem cells with all the abilities of self-r.
