Mesenchymal stem cell-derived exosome: The likely game-changer in stem cell research DICKSON KOFI WIREDU OCANSEY 1,2, *;XINWEI XU 1 ;LU ZHANG 1 ;FEI MAO 1, * 1 Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, China 2 Directorate of University Health Services, University of Cape Coast, Cape Coast, Ghana Key words: Mesenchymal stem cell, Exosome, Cell-free therapy, Regenerative medicine Abstract: Stem cell research is a promising area of transplantation and regenerative medicine with tremendous potential for improving the clinical treatment and diagnostic options across a variety of conditions and enhancing understanding of human development. Over the past few decades, mesenchymal stem cell (MSCs) studies have exponentially increased with a promising outcome. However, regardless of the huge investment and the research attention given to stem cell research, FDA approval for clinical use is still lacking. Amid the challenges confronting stem cell research as a cell- based product, there appears to be evidence of superior effect and heightened potential success in its expressed vesicles, exosomes, as cell-free products. In addition to their highly desirable intrinsic biologically unique structural, compositional, and morphological characteristics, as well as predominant physiochemical stability and biocompatibility properties, exosomes can also be altered to enhance their therapeutic capability or diagnostic imaging potential via physical, chemical, and biological modification approaches. More importantly, the powerful therapeutic potential and superior biological functions of exosomes, particularly, regarding engineered exosomes as cell-free products, and their utilization in a new generation of nanomedicine treatment, vaccination, and diagnosis platforms, brings hope of a change in the near future. This viewpoint discusses the trend of stem cell research and why stem cell-derived exosomes could be the game-changer. Introduction The concept of stem cells emanated in the 19th century as a theoretical postulate that accounted for the ability of certain tissues including, blood and skin to self-renew for the lifetime of an organism. The discovery of stem cells as individually separate and distinct cellular entities followed many years later as a result of developed methods for their prospective isolation, in addition to rigorous bioassays designed to test their potency (Bianco et al., 2008). The currently popular concept of mesenchymal stem cells (MSCs), a term first coined by Caplan, is traced to classical experiments of bone marrow transplantation that caused de novo formation of ectopic bone and marrow (Caplan, 1991). Over the past 20 years, research on MSCs has exponentially increased (Fig. 1) due to the promising treatment outcome for a variety of human diseases including, cardiovascular diseases, blood malignancies, metabolic diseases (diabetes, obesity), bone regeneration and arthritis, neurodegenerative disease, and several inflammatory diseases, as they potently differentiate into osteoblasts, adipocytes, and chondrocytes and exhibit the potential to regenerate damaged tissues (Farahzadi et al., 2020; Fu et al., 2019). Moreover, the therapeutic potentials of MSCs are maintained and even further enhanced via modifications against the inhospitable microenvironment during culture and transplantation, resulting in improved migration, homing to target site, adhesion, survival, and reduced premature senescence (Nie et al., 2020; Ocansey et al., 2020a). There are several completed and ongoing clinical trials at different phases, involving therapeutics of MSCs across many human diseases. However, irrespective of the huge investment and the attention given to stem cell research, approval for clinical use is still lacking. Amidst the challenges confronted by stem cell research as a cell-based product, there appears to be a gradual paradigm shift from stem cell-based research to its derived exosomes and exosomes from other sources as a cell-free product. After the discovery that exosomes are responsible for the therapeutic effects of MSCs, huge attention has been shifted towards these extracellular *Address correspondence to: Fei Mao, maofei2003@ujs.edu.cn; Dickson Kofi Wiredu Ocansey, dickson.ocansey@ucc.edu.gh Received: 26 July 2021; Accepted: 26 September 2021 BIOCELL ech T Press Science 2022 46(5): 1169-1172 Doi: 10.32604/biocell.2022.018470 www.techscience.com/journal/biocell This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.