Mesenchymal stem cell-derived peptides (MSC-DPs) are increasingly recognized as pivotal mediators of MSC paracrine activity, providing a strictly defined, cell-free alternative to conventional whole-cell therapies. Current evidence, largely derived from in vitro and preclinical animal models, indicates that these low-molecular-weight peptides exert potent immunomodulatory, angiogenic, cytoprotective, and metabolic effects facilitating tissue repair. Peptidomic analyses of both human and xenogenic MSC sources have identified conserved peptide motifs enriched in cysteine-, glycine-, and proline-rich sequences, indicating robust potential for cross-species biological activity. Experimental data support the efficacy of MSC-DPs in enhancing epithelial repair, modulating macrophage polarization, and improving vascular responses; however, early translational observations remain limited and largely exploratory. Despite growing interest, progress toward clinical translation is constrained by substantial heterogeneity in MSC sources, isolation protocols, culture conditions, and peptide characterization methods, which complicate systematic comparisons across studies. Furthermore, a limited understanding of sequence–function relationships, coupled with challenges in peptide stability and in vivo delivery, further restricts therapeutic development. Continued advances in proteomics, computational prediction, and biomaterial-based delivery systems are expected to significantly improve the identification, standardization, and formulation of MSC-DPs. Overall, MSC-DPs represent a rapidly developing frontier in regenerative medicine with robust mechanistic foundations, yet their clinical translation will require rigorous validation and the harmonization of methodological approaches.
Agha et al. (Thu,) studied this question.