PriMera Scientific Surgical Research and Practice (ISSN: 2836-0028)

Research Article

Volume 7 Issue 1

Age-Related Decline in Mesenchymal Stem Cells: Implications for Degenerative Disease Burden and Regenerative Medicine Strategies

Connor Wu and Gordon Slater*

December 18, 2025

DOI : 10.56831/PSSRP-07-234

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Abstract

Mesenchymal stem/stromal cells (MSCs) exhibit the most dramatic age-related decline among adult stem cell populations, decreasing 100-to 1,000-fold in frequency and suffering profound functional impairment in proliferation, differentiation, immunomodulation, and paracrine activity. Normalized epidemiological data reveal a striking inverse relationship across the human lifespan: as MSC levels plummet between the third and sixth decades, the incidence and prevalence of major degenerative diseases; osteoarthritis requiring total knee/hip replacement, cardiovascular disease, and cancer, rise exponentially (Figure 1). Unlike hematopoietic, neural, muscle, or intestinal stem cells, which primarily undergo qualitative deterioration or protective quiescence while preserving cell numbers, MSCs experience both quantitative depletion and senescence without compensatory mechanisms. Their primary physiological role is not direct lineage replenishment but orchestration of tissue repair through secreted growth factors, anti-inflammatory mediators, and extracellular vesicles that support resident progenitor cells and resolve chronic inflammation. Many clinical trials now demonstrate that administration of culture-expanded autologous or allogeneic MSCs, particularly from younger donors, safely reduces pain and improves function in knee osteoarthritis, modestly enhances cardiac performance post-infarction, and induces remission in steroid-refractory inflammatory diseases, with effect size correlating with donor age and cell dose. These findings strongly suggest that the precipitous loss of functional MSCs constitutes a pivotal, upstream bottleneck in endogenous regenerative capacity and a rational cross-disease therapeutic target. Strategies to restore youthful MSC activity via allogeneic cells from perinatal sources, pharmacological mobilisation, exosome-based therapeutics, or rejuvenation of autologous cells hold promise for mitigating the escalating burden of age-related degenerative pathology and warrant prioritisation in late-stage clinical investigation.

Keywords: Regenerative Medicine; Osteoarthritis; Stem Cells; Mesenchymal Stem Cells

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