PDGFRβ in Stem Cell Microenvironments: Cross-Tissue Evidence and Hypotheses for the Limbal Stem Cell Niche

Stem cells reside within specialized microenvironments, termed niches, composed of vascular networks, stromal cells, extracellular matrix (ECM), immune components, and neural elements, which collectively regulate quiescence, self-renewal, and lineage commitment of stem cells. Platelet-derived growth factor receptor-β (PDGFRβ), a class III receptor tyrosine kinase (RTK) predominantly expressed in perivascular and mesenchymal stromal cells, has been associated with vascular-stromal organization across multiple stem cell systems. Rather than acting mainly as a direct determinant of stemness-associated transcriptional programs, PDGFRβ may influence stem cell behavior indirectly by modulating vascular stability, matrix remodeling, metabolic gradients, and biomechanical signaling. Evidence from hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), neural stem cells (NSCs), tumor stem cells (TSCs), renal glomerular cells, and limbal stem cells (LSCs) indicates that PDGFRβ⁺ stromal or perivascular cells contribute to niche architecture and function in a context-dependent manner. Through interactions with platelet-derived growth factor-B (PDGF-B), vascular endothelial growth factor (VEGF), hypoxia-related signaling, inflammatory mediators, and integrin-dependent mechanotransduction, PDGFRβ is linked to angiogenesis, stromal cell activation, ECM remodeling, and niche biomechanics. Under physiological conditions, such regulation may support tissue maintenance, repair, and regeneration, whereas persistent or dysregulated activation may contribute to fibrosis, vascular dysfunction, tumor progression, and disruption of stem cell equilibrium. This review summarizes the current understanding of PDGFRβ as a vascular-stromal component associated with stem cell niche regulation, with emphasis on cross-tissue mechanisms and context-dependent differences. Particular attention is given to the LSC niche, where PDGFRβ⁺ limbal niche cells (LNCs) are discussed in relation to the Palisades of Vogt, limbal vessels, basement membrane/ECM organization, and epithelial progenitor maintenance. We distinguish established evidence for PDGFRβ expression and LNC-associated stromal identity from proposed mechanisms involving vascular-stromal support, ECM remodeling, biomechanical regulation, and LSC repair. Because receptor-specific functional evidence for PDGFRβ in limbal microenvironmental cells remains limited, the limbal component of this review is presented as a hypothesis-generating framework rather than as established evidence that PDGFRβ functionally regulates the limbal niche. Collectively, available evidence supports PDGFRβ as a candidate link between vascular-stromal organization and stem cell functional states, while underscoring the need for direct PDGFRβ perturbation studies in LNCs to define its functional relevance in limbal niche stability and corneal epithelial regeneration. This framework may guide future studies of PDGFRβ-associated stromal regulation in corneal epithelial regeneration and LSC niche dysfunction.