Secretome of Stem Cells: Roles of Extracellular Vesicles in Diseases, Stemness, Differentiation, and Reprogramming

Abstract

Increasing evidence suggests that stem cells or stem cell-derived cells may contribute to tissue repair, not only by replacing lost tissue but also by delivering complex sets of secretory molecules, called secretomes, into host injured tissues. In recent years, extracellular vesicles (EVs) have gained much attention for their diverse and important roles in a wide range of pathophysiological processes. EVs are released from most types of cells and mediates cell-cell communication by activating receptors on target cells or by being taken up by recipient cells. EVs, including microvesicles and exosomes, encapsulate and carry proteins, nucleic acids, and lipids in the lumen and on the cell surface. Thus, EV-mediated intercellular communication has been extensively studied across various biological processes. While a number of investigations has been conducted in different tissues and body fluids, the field lacks a systematic review on stem cell-derived EVs, especially regarding their roles in stemness and differentiation. Here, we provide an overview of the pathophysiological roles of EVs and summarize recent findings focusing on EVs released from various types of stem cells. We also highlight emerging evidence for the potential implication of EVs in self-renewal, differentiation, and reprograming and discuss the benefits and limitations in translational approaches.

Keywords: Differentiation; Extracellular vesicles; Secretome; Stem cell; Stemness.

Fig. 1

Schematic of the diverse roles of EVs modulating pathophysiological and cellular processes. A Biogenesis, potential cargos, and action modes of EVs (microvesicles, exosomes, and apoptotic bodies). Exosomes are formed in early endosomes, which subsequently produce MVBs. MVBs release exosomes into the extracellular space by exocytosis. Microvesicles are formed and released by outward budding and shedding of the plasma membrane. Apoptotic bodies are enclosed vesicles produced from apoptotic cells by membrane blebbing. EVs mediate cell–cell communications by activating receptors on target cells or being taken up by recipient cells, thus releasing their cargo inside the cells. EVs are also transported through systemic circulation and deliver their contents to distant tissues. B Pathophysiological implication of EVs in inflammation, adaptive immunity, cancer, aging, and degenerative diseases. C Potential roles of stem cell-derived EVs in early development of embryos, biological processes, and stemness/differentiation of stem cells. EVs extracellular vesicles, MVB multi-vesicular bodies, SC stem cell, ESCs embryonic stem cells, iPSCs induced pluripotent stem cells, MSC multipotent stem cells, TSCs tissue-specific stem cells, HSC hematopoietic stem cells, PSC, pluripotent stem cell, NPC neural progenitor cells