Mesenchymal Stem Cell-Derived Secretome: A Potential Therapeutic Option for Autoimmune and Immune-Mediated Inflammatory Diseases

Abstract

Immune-mediated inflammatory diseases (IMIDs) encompass several entities such as “classic” autoimmune disorders or immune-mediated diseases with autoinflammatory characteristics. Adult stem cells including mesenchymal stem cells (MSCs) are by far the most commonly used type in clinical practice. However, due to the possible side effects of MSC-based treatments, there is an increase in interest in the MSC-secretome (containing large extracellular vesicles, microvesicles, and exosomes) as an alternative therapeutic option in IMIDs. A wide spectrum of MSC-secretome-related biological activities has been proven thus far including anti-inflammatory, anti-apoptotic, and immunomodulatory properties. In comparison with MSCs, the secretome is less immunogenic but exerts similar biological actions, so it can be considered as an ideal cell-free therapeutic alternative. Additionally, since the composition of the MSC-secretome can be engineered, for a future perspective, it could also be viewed as part of a potential delivery system within nanomedicine, allowing us to specifically target dysfunctional cells or tissues. Although many encouraging results from pre-clinical studies have recently been obtained that strongly support the application of the MSC-secretome in IMIDs, human studies with MSC-secretome administration are still in their infancy. This article reviews the immunomodulatory effects of the MSC-secretome in IMIDs and provides insight into the interpretation of its beneficial biological actions.

A novel therapeutic management for diabetes patients with chronic limb-threatening ischemia: comparison of autologous bone marrow mononuclear cells versus allogenic Wharton jelly-derived mesenchymal stem cells

“…Finally, stem cell treatment may sometimes encounter ethical obstacles or biological restrictions. Thus, in recent years, it has been thought that the released secretomes, composed of biologically active molecules (growth factors, cytokines and chemokines, angiogenic factors, extracellular matrix proteins, proteases, and genetic material secreted from stem cells), have revealed a considerable capacity for repair and regeneration of damaged cell membranes, or induce the secretion of surrounding tissues could reveal a new approach for the cell-free treatment [44][45][46].…”

Role of Mesenchymal Stem Cells and Their Paracrine Mediators in Macrophage Polarization: An Approach to Reduce Inflammation in Osteoarthritis

“…According to recent studies, EV density and load might also be modified by employing hypoxic preconditioning. However, hypoxia seemed to have no effect on the mean size, morphology, or surface biomarkers of MSC-derived EVs [ 183 ]. In response to hypoxia and serum deprivation, primed MSCs produced more dipeptides, suggesting that hypoxic MSCs augment their pool of free amino acids to meet energy requirements that cannot be properly met by the glycolytic process.…”

Mesenchyme Stem Cell-Derived Conditioned Medium as a Potential Therapeutic Tool in Idiopathic Pulmonary Fibrosis

“…Moreover, MSCs produce soluble proteins like chemokines and cytokines that enhance the cells’ pathological responses. The proteins include immunomodulatory impact due to the indirect and direct effects on different immune cells and response to cell or tissue injury [ 33 ]. Secretome contains cytokines and growth factors like hepatocyte growth factor (HGF), transforming growth factor-beta isoform 3 (TGF-b3), IL-10, and tumor necrosis factor-alpha (TNF-a), which moderate cell signaling and fibrogenesis processes [ 34 ].…”

“…Thus, the possibility of using MSCs-derived CM in clinical studies may have a wide range of advantages over the use of stem cell therapy [ 33 ]. Administration of CM derived from in vitro cultures of stem cells, containing their secretory products, has been shown to repair tissues, in a similar way to stem cell therapy, and their effects may be associated with the modulation of the immune responses [ 36 , 37 , 38 ].…”