Abstract
The progressive loss of the regenerative potential of tissues is one of the most obvious consequences of aging, driven by altered intercellular communication, cell senescence and niche-specific stem cell exhaustion, among other drivers. Mesenchymal tissues, such as bone, cartilage and fat, which originate from mesenchymal stem cell (MSC) differentiation, are especially affected by aging. Senescent MSCs show limited proliferative capacity and impairment in key defining features: their multipotent differentiation and secretory abilities, leading to diminished function and deleterious consequences for tissue homeostasis. In the past few years, several interventions to improve 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 based on the potential use of young allogeneic MSCs and derivatives, such as extracellular vesicles (EVs), are gaining attention. Based on encouraging pre-clinical and clinical data, this review assesses the strong potential 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 and the possibility of enhancing their clinical potential by exposing MSCs to niche-relevant signals.
Highlights
Aging, an inexorable consequence of life, can be defined by a time-dependent loss of cellular and molecular homeostasis, leading to impaired function of tissues and organs that are unable to activate proper compensatory mechanisms to restore the lost functionality [1]
The personal, social and economic burden of age-related pathologies have long been an increasing public health concern, a fact dramatically revealed with the current COVID-19 pandemic especially affecting the elderly
mesenchymal stem cell (MSC)-based therapies emerge as quite a compelling option to counteract aging, one that deserves further research
Summary
An inexorable consequence of life, can be defined by a time-dependent loss of cellular and molecular homeostasis, leading to impaired function of tissues and organs that are unable to activate proper compensatory mechanisms to restore the lost functionality [1]. MSCs can migrate to the injured tissue and differentiate into specific cell types, their main therapeutic effect is thought to be paracrine, by secreting bioactive factors depending on the microenvironment they face, known as a hit-andrun mechanism [4,9,10]. Along these lines, the first studies using MSCs as a therapy in pediatric patients affected by the rare bone disorder, osteogenesis imperfecta, showed that after in vivo administration, the engraftment of MSCs in target tissues such as bone was anecdotal, beneficial effects were found [11]. We shed light on the coming advanced therapeutic avenues to prevent age-related pathologies and extend the healthspan, that is, the diseasefree period, in a human lifetime
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