The Use of PRP, Exosomes, and Stem Cells in Testicular Rejuvenation: Mechanisms, Evidence and Clinical Translation

Panayiotis Zavos.

Abstract

This comprehensive review examines autologous platelet-rich plasma (PRP), mesenchymal stem cells (MSCs) and their derivatives (including exosomes), and spermatogonial stem cells (SSCs) as regenerative therapies for the human testes. We analyze mechanistic pathways (PI3K/Akt, Wnt/β-catenin, TGF-β/SMAD, JAK/STAT, MAPK, oxidative stress, autophagy) by which these therapies may enhance Sertoli cell support, Leydig cell function, and germ cell survival. Preclinical evidence is summarized in tables: for example, in a rat ischemia–reperfusion model, PRP post conditioning markedly reduced oxidative markers and preserved seminiferous tubule histology [1]. Another table compares animal studies (species, injury model, intervention, outcomes). We detail how exosomes (nanovesicles from PRP or MSCs) deliver miRNAs and proteins to testicular cells, noting that MSC-derived exosomes outperformed PRP in restoring spermatogenesis in busulfan-induced azoospermia [2]. Stem cell therapies are evaluated: MSCs can differentiate into germ?like cells and secrete trophic factors, while SSC transplantation (experimental) may directly replenish spermatogenesis. We compare modalities: PRP is autologous and easy to administer but variable, MSC/exosomes offer potent paracrine effects but face standardization and safety hurdles. Clinical evidence is still early: one study reported that testicular PRP injections in oligoasthenoteratozoospermia improved sperm count and motility [3]. However, human data are limited and heterogeneous. We discuss limitations (tumorigenicity, regulatory issues, lack of long?term data) and conclude that these therapies show promise but cannot yet fully restore fertility. Exosome therapy may be most promising long-term. Key gaps include standardized protocols, clarity on mechanisms, and randomized trials. Future research should focus on rigorous clinical studies, combination approaches, and detailed mechanistic understanding.