Aging populations are increasing the incidence of age-related diseases, resulting in problems at the individual and socioeconomic level. The need for effective strategies in regenerative medicine for the elderly is more important than ever. Previous studies have shown that the number and function of stem cells decline with age, thereby undermining endogenous repair processes.
Stem Cells for Anti-Aging and Rejuvenation
Aging-related tissue changes and stem cell depletion in mammals lead to imbalances in tissue homeostasis and decreased organ regenerative capacity. The mediation of aging by complex cellular and physiological processes is driven by various acquired and genetic factors. The physiological processes of aging often lead to destructive diseases, such as dementia, autoimmunity, arthritis, cardiovascular disease, cancer, tissue degeneration, neuropathy, stroke, obesity, and depression . The effects of aging are particularly noticeable in retarded eyesight, hearing, muscle strength, and bone strength. Regenerative medicine can reverse or inhibit many of these health problems through the use of endogenous stem cells or exogenous replacement cells derived from stem or progenitor cells to restore or rejuvenate tissue and maintain homeostasis.
Stem cells are characterized by their multiple-efficacy and self-renewal capabilities, resulting in progenitor or mature cells that can repair tissue and retain the characteristics of stem cells to ensure long-term maintenance of the stem cell pool. As stem cells age, their renewal ability deteriorates, and their ability to differentiate into various cell types is depleted. Based on current understanding of stem cells, it is feasible to design and test interventions to slow aging and improve health and longevity. It is believed that stem cell failure contributes to a decline in health during aging; therefore, the development of effective methods to induce and differentiate pluripotent stem cells via cell replacement therapy provides an exciting avenue for the treatment of degenerative age-related diseases. It is believed that the regenerative potential of these cells is due to their high proliferation and differentiation capabilities, paracrine activity, and immune privilege . Somatic stem cell populations differ according to the regenerative needs of the host tissue. In high turnover tissue, such as the gut or hematopoietic system, most stem cell or progenitor cell populations are active throughout life . In organs lacking stem cells, inducing pluripotent stem cell (iPSC) to replace cells is a promising therapeutic approach for functional recovery. iPSCs restore the same developmental potential of embryonic stem cells, which means that they can then differentiate into any type of tissue. Stem cells play a key role in organogenesis and maintaining homeostasis throughout life, possess the ability to migrate long distances and target pathological conditions, express therapeutic genes, and respond to cues that redirect their differentiation into defective lineages . This means that stem cells can be used for cell replacement as a therapeutic intervention aimed at mitigating the effects of aging.
For decades, research proceeded on the assumption that the nervous system of adult mammals is unable to produce new neurons. However, the identification of neurogenic regions in the adult brain has prompted intense activity in the field of adult neurogenesis. Most neurons are mitotic, and slow-cycle neural stem cells (NSC) maintain neural regeneration in specific areas of the mammalian brain during adulthood. Age-induced reduction in the number of satellite cells and neural stem cells undermines nerve regeneration. Aging of the central nervous system is associated with the progressive loss of function, which can be exacerbated by neurodegenerative diseases, such as Alzheimer’s disease, dementia, stroke, and Parkinson’s disease. At the cellular level, senescence of the central nervous system is accompanied by a number of changes that impair cell function, including elevated levels of oxidative stress and oxidative damage associated with proteins and DNA. It has also been linked to impaired cellular metabolism, lipid and protein by-products, and the accumulation of advanced glycation end products. The most notable age-related changes in the brain are associated with cognition and plasticity. Even in the absence of disease, aging can negatively affect nerve function. Recent data suggest that age-related defects in neural stem cells can be reversed through the reactivation of telomerase, suggesting that aged oligodendrocyte precursor cells can theoretically be used to preserve the regeneration of myelin sheaths. In the adult central nervous system, remyelination is a spontaneous regenerative process that restores skip conduction, prevents axonal degeneration, and promotes functional recovery.
Nerve System Rejuvenation
Most previous studies reported that cell therapy may be able to replenish lost cells and promote neuronal regeneration, protect neuron survival as well as play a role in overcoming permanent paralysis and sensory loss and restoring neurological function. Unfortunately, mechanisms for determining treatment capacity have yet to be identified. Previously researches implied that possible mechanisms may include the following:
1) the promotion of angiogenesis
2) induced neuronal differentiation and neurogenesis
3) reduced reactive gliosis
4) the inhibition of apoptosis
5) the expression of neurotrophic factors
6) immunomodulatory functions
7) the promotion of neuronal integration.
The two primary cell replacement strategies involve
1) the transplantation of exogenous tissue and
2) the endogenous activation of cell proliferation. Tissue can be transplanted directly in order to replace lost tissue. Genetically engineered cells can also be implanted for the secretion of factors that promote survival and/or proliferation
The specialized microenvironment of the neural niche ensures that neural stem cells (NSCs) self-renew and differentiate but mainly enter the neurons. Thus, understanding the physiological characteristics of NSCs and how they are affected by changes in pathological conditions could open the door to exploiting the plasticity of NSCs for the prevention and/or treatment of degenerative diseases.
Articular Cartilage Rejuvenation
Articular cartilage injury is a debilitating disease that can result in fibrillation and the subsequent deterioration of the peripheral articular surface and may also involve the subchondral bone, thereby facilitating the development of osteoarthritis. The special composition of the ECM gives it viscoelastic properties, which facilitate the normal function of the ECM. Collagen is hyaline cartilage composed of 60% (by dry weight) chondrocytes. Fibrocartilage and elastic cartilage are two other types of cartilage differing in ECM and cell components. Age-induced changes in articular cartilage include chondrocytes acquiring a secretory phenotype, chondrocyte sensitivity to growth factors, the destructive effects of chronic ROS, and glycosylation of end products. This disturbs the balance between anabolic activity and the destructive processes of chondrocytes. As the matrix decreases, articular cartilage becomes increasingly thin, the hydration of cartilage decreases, and the number of cartilage cells also decreases. It appears that the bioactive paracrine factors secreted by mesenchymal stem cells (MSC) can have beneficial effects in regulating the microenvironment of damaged tissue, leading to more favorable conditions for tissue regeneration. MSCs secrete a range of paracrine factors, collectively referred to as se-creted proteomes, which perform a variety of biological functions, including immune regulation, angiogenesis, anti-apoptosis, anti-oxidation, cell homing, and the promotion of cell differentiation. Most previous studies have focused on the clinical benefits of MSC treatment, regardless of the source of the cells, the indications, or the mode of administration. MSCs have been used in cell therapy to promote the repair of cartilage, muscle, or bone. These cells are typically harvested from bone marrow and are characterized according to the stimulatory factors they provide. Elucidating the mechanism that promotes the aging of articular cartilage could lead to treatments aimed at slowing aging-related changes or promoting the regeneration of articular cartilage.
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