Researchers here review the state of stem cell therapies for the treatment of age-related degenerative conditions, with particular attention to more recently emerged areas of the field such as efforts to rejuvenate old patient-derived stem cells before their use in therapy. Partial epigenetic reprogramming is not much mentioned in this context as, unlike the use of senolytics, it has not yet advanced to the point of ease of use for the average stem cell clinic. Treating a stem cell culture with cheap and well-established senolytic compounds is very much more feasible in comparison to the time, expertise, and expense needed to safely and reliably partially reprogram cells in that same culture.
Rejuvenation strategies for ageing stem cells focus on restoring their regenerative capabilities, which decline with age, to improve tissue homeostasis and potentially extend health and lifespan. Various pathways regulate the rejuvenation process in the body, but impairment of these pathways can lead to poor stem cell function. Although the body has various pathways, recent trends have new approaches to managing stem cells via new rejuvenation strategies. The primary methods for rejuvenation strategies for stem cells include (a) preconditioning and senolytics, and (b) biomaterials and engineered niches.
Environmental or chemical preconditioning can help in the regeneration of stem cells by increasing proliferation, differentiation, and stress resistance. Hypoxic culture, growth factor priming, and expansion on youth-mimicking matrices, such as decellularised extracellular matrix, are among the techniques to boost mesenchymal stem cells (MSCs) and other stem cell types for renewal. Senolytic drugs, for example, quercetin, fisetin, and dasatinib, selectively remove the senescent cells, and thus lower senescence-associated secretory phenotype (SASP) levels while restoring stem cell and their lineage potential. The drug quercetin showed the removal of senescent MSCs, leading to the enhancement of their proliferating and osteogenic capability, simultaneously inhibiting adipogenesis, adding other strong evidence to the senolytic approach of stem cell rejuvenation. Additionally, MSC exosomes exhibit immunomodulatory, antioxidant and reparative potential on senescent cells.
Engineered niches like scaffolds, decellularized matrices, and hydrogels, can replicate a juvenile extracellular environment to keep the stem cells viable. MSC-loaded chitosan hydrogels, along with MSC exosomes, enhanced fibroblast function, thereby increasing proliferation and collagen formation while reducing matrix metalloproteinases and SASP factors and rejuvenating skin in older mice. Biomaterial carriers enhance transplanted cell survival by mimicking extracellular matrix signals like adhesion ligands, sequestered growth factors, and mechanical stiffness that ultimately led to better engraftment and regenerative efficiency.
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