Neuro-immune-vascular-stem cell crosstalk in bone/cartilage regeneration: mechanisms, technological advances, and clinical perspectives.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Functional regeneration of bone and cartilage remains an urgent clinical challenge in orthopedics, as its repair process involves the synergistic participation of multiple systems and cell types. Traditional studies have mostly focused on the regulatory roles of individual cells or signaling pathways, while recent research has confirmed that bone/cartilage regeneration is governed by a regulatory mechanism centered on the neuro-immune-vascular axis. In this mechanism, mesenchymal stem cells (MSCs), bone marrow mesenchymal stem cells (BMSCs), adipose-derived mesenchymal stem cells (ADSCs), and cartilage progenitor cells (CPCs) serve as key functional cells, interacting sequentially and transcellularly with immune cells and endothelial cells through multiple core signaling pathways. This review systematically summarizes these core signaling pathways, including neurosignal-mediated pathways (CGRP/ CRLR , NGF / TrkA , SP/ NK1R ), immune signal-mediated pathways ( IL-4 / IL-4R , TGF-β /Smad, TNF-α / NF-κB ), endothelial cell-mediated pathways ( VEGF / VEGF R, Notch, PDGF / PDGF R), and cross-regulatory pathways ( PI3K / Akt , MAPK ). These pathways collectively mediate the sequential crosstalk and functional coordination among the four cellular components. Additionally, the review highlights the application achievements of cutting-edge technologies in this field, such as single-cell

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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