Cellular microenvironment: a key for tuning mesenchymal stem cell senescence

Abstract

Mesenchymal stem cells (MSCs) possess the ability to self-renew and differentiate into multiple cell types, making them highly suitable for use as seed cells in tissue engineering. These can be derived from various sources and have been found to play crucial roles in several physiological processes, such as tissue repair, immune regulation, and intercellular communication. However, the limited capacity for cell proliferation and the secretion of senescence-associated secreted phenotypes (SASPs) pose challenges for the clinical application of MSCs. In this review, we provide a comprehensive summary of the senescence characteristics of MSCs and examine the different features of cellular microenvironments studied thus far. Additionally, we discuss the mechanisms by which cellular microenvironments regulate the senescence process of MSCs, offering insights into preserving their functionality and enhancing their effectiveness.

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

“…Numerous studies demonstrate a strong correlation between p65 and its paracrine effects. Comparable levels of p65, IL-6, and IL-8 are observed in both DNA damage-induced MSC senescence, indicating p65 pathway activation in MSCs …”

“…Comparable levels of p65, IL-6, and IL-8 are observed in both DNA damage-induced MSC senescence, indicating p65 pathway activation in MSCs. 57 2.2.2. Extrinsic Microenvironment Effect on MSCs Senescence.…”

Regulation of bone homeostasis: signaling pathways and therapeutic targets

“… 298 An increase in bone marrow adipocytes further exacerbates the development of osteoporosis, which not only impedes osteoblastogenesis but also favors osteoclastogenesis through the activation of PPARγ by free fatty acids (FFAs). 299 Palmitic acid, a specific FFA, notably hinders osteoblast development and mineralization by suppressing the Wnt/β‐catenin and BMP2/RUNX2/SMAD pathways and induces apoptosis and autophagy dysfunction in osteoblasts. 300 In addition, the interaction of PPARγ with specific promoter elements in hematopoietic stem cells promotes osteoclastogenesis, 301 highlighting the complex interplay between factors that drive the progression of osteoporosis.…”