Targeting the stem cell niche micro-environment as therapeutic strategies in aging

Abstract

Adult stem cells (ASCs) reside throughout the body and support various tissue. Owing to their self-renewal capacity and differentiation potential, ASCs have the potential to be used in regenerative medicine. Their survival, quiescence, and activation are influenced by specific signals within their microenvironment or niche. In better words, the stem cell function is significantly influenced by various extrinsic signals derived from the niche. The stem cell niche is a complex and dynamic network surrounding stem cells that plays a crucial role in maintaining stemness. Studies on stem cell niche have suggested that aged niche contributes to the decline in stem cell function. Notably, functional loss of stem cells is highly associated with aging and age-related disorders. The stem cell niche is comprised of complex interactions between multiple cell types. Over the years, essential aspects of the stem cell niche have been revealed, including cell-cell contact, extracellular matrix interaction, soluble signaling factors, and biochemical and biophysical signals. Any alteration in the stem cell niche causes cell damage and affects the regenerative properties of the stem cells. A pristine stem cell niche might be essential for the proper functioning of stem cells and the maintenance of tissue homeostasis. In this regard, niche-targeted interventions may alleviate problems associated with aging in stem cell behavior. The purpose of this perspective is to discuss recent findings in the field of stem cell aging, heterogeneity of stem cell niches, and impact of age-related changes on stem cell behavior. We further focused on how the niche affects stem cells in homeostasis, aging, and the progression of malignant diseases. Finally, we detail the therapeutic strategies for tissue repair, with a particular emphasis on aging.

Fructose vs. Glucose: Modulating Stem Cell Growth and Function Through Sugar Supplementation

“…They greatly vary not only in their origins but also in their potency 6 . This can be attributed partially to the special microenvironment surrounding them that contains the required nutrient, oxygen level, and cytokines suitable for survival and differentiation 4,6 . Any change in the pericellular environment will consequently modulate cell signals, cytokines, that will act directly on the cell itself (autocrine effect) or neighboring cells (paracrine effect) 3,4,6 .…”

“…However, the acessibility of these resources in the pericellular environment greatly varies from organ to organ 3–5 . This divergence in resource availability leads to variations in the potency and differentiation potential of stem cells 4,6 . Moreover, hexose and oxygen levels modulate cytokine production which is crucial for cell-cell communication 7,8 as well as growth, and differentiation of stem cell 9,10 . Hence, this study aims to explore the distinct effects of glucose and fructose, as well as different oxygen tensions, on the growth dynamics, cytokine production, and differentiation of stem cells.…”

Emerging Landscape of Mesenchymal Stem Cell Senescence Mechanisms and Implications on Therapeutic Strategies

“…By regulating the stem cell niche, we can create a favorable microenvironment for mesenchymal stem cells, thus potentially attenuating agingrelated changes and enhancing their regenerative capacity for therapeutic use. 98 Further research is crucial to optimize niche modulation strategies and translate them into clinically applicable therapies for age-related ailments and tissue injuries. Combining these approaches can address weaknesses and deficiencies, ultimately rejuvenating mesenchymal stem cells (see Figure 7).…”

Skeletal Muscle Stem Cells Modulate Niche Function in Duchenne Muscular Dystrophy through YY1-CCL5 Axis

“…In fact, it is safe to state that in general our understanding about if and how tissue adult stem cells impact their niches is very limited. Across a variety of well-studied adult stem cells such as mesenchymal stem cells (MSCs), hematopoietic stem cells (HSs) and neural stem cells (NSCs) etc., we have learnt plenty about the essential roles of the stem cell niche in regulating stem cell behavior and functionality( 24 ), including how alteration in the stem cell niche causes cellular damage and impairs the regenerative capacity of stem cells. In principle the stem cells are perceived as the passive recipient of niche signals and impact.…”