This review examines the synergistic effects and mechanisms of Traditional Chinese Medicine (TCM) and its extracts on mesenchymal stem cells (MSCs), with a focus on enhancing MSC proliferation, differentiation, and immunomodulation for therapeutic applications. A comprehensive analysis of studies from the past five years was conducted, evaluating interactions between TCM/extracts and MSC types (bone marrow-, adipose-, and umbilical cord-derived MSCs) through molecular pathways (e.g., PI3K/Akt, Wnt/β- catenin, TGF-β/Smad) and microRNA regulation. In vitro, in vivo, and clinical trial data were synthesized. TCM and extracts significantly upregulated osteogenic/adipogenic differentiation in bone marrow mesenchymal stem cells via miR-335-5p/PTEN and Runx2 pathways, enhanced the viability of adipose-derived mesenchymal stem cells under oxidative stress via Sirt1/Akt activation, and improved the immunomodulation of umbilical cord mesenchymal stem cells by increasing anti-inflammatory factors (HGF, PGE2). Combined MSC-TCM therapies accelerated diabetic ulcer healing (via the miR-146A-NF-κB axis), reduced liver fibrosis (via miR-19b-3p), and mitigated stroke/arthritis symptoms. TCM synergizes with MSCs through multipathway crosstalk and miRNA regulation, amplifying therapeutic efficacy in degenerative, inflammatory, and ischemic diseases. Clinical translation requires standardized TCM dosing and large-scale trials to validate safety and the durability of mechanistic effects. Specifically, the combination of Icariin and BMSCs for bone disorders, and resveratrol combined with ADSCs for diabetic complications, has demonstrated remarkable synergistic effects, thus highlighting their potential as priorities for future clinical translation.
Fang et al. (2026) studied this question.