Wharton’s jelly mesenchymal stem cells: a concise review of their secretome and prospective clinical applications

Abstract

Accumulating evidence indicates that most primary Wharton’s jelly mesenchymal stem cells (WJ-MSCs) therapeutic potential is due to their paracrine activity, i.e., their ability to modulate their microenvironment by releasing bioactive molecules and factors collectively known as secretome. These bioactive molecules and factors can either be released directly into the surrounding microenvironment or can be embedded within the membrane-bound extracellular bioactive nano-sized (usually 30–150 nm) messenger particles or vesicles of endosomal origin with specific route of biogenesis, known as exosomes or carried by relatively larger particles (100 nm–1 μm) formed by outward blebbing of plasma membrane called microvesicles (MVs); exosomes and MVs are collectively known as extracellular vesicles (EVs). The bioactive molecules and factors found in secretome are of various types, including cytokines, chemokines, cytoskeletal proteins, integrins, growth factors, angiogenic mediators, hormones, metabolites, and regulatory nucleic acid molecules. As expected, the secretome performs different biological functions, such as immunomodulation, tissue replenishment, cellular homeostasis, besides possessing anti-inflammatory and anti-fibrotic effects. This review highlights the current advances in research on the WJ-MSCs’ secretome and its prospective clinical applications.

Extracellular Vesicles and Hydrogels: An Innovative Approach to Tissue Regeneration

“…However, there is some size overlap between these two types of vesicles. The generation of MVs is an intricate process that involves the redistribution of phospholipids and the contraction of cytoskeletal proteins . The distribution of phospholipids in the plasma membrane is asymmetrical and rigorously controlled by aminophospholipid translocases, such as flippases and floppases.…”

Regulation of immune responses to infection through interaction between stem cell-derived exosomes and toll-like receptors mediated by microRNA cargoes

“…Consequently, examination of miRNAs expression in T-MSCs revealed that the significant downregulation of inflammatory cytokines in treated HMC-1 cells in the presence of T-MSC exosomes may be associated with the overexpression of miR-214-3p, miR-424-5p, miR-126-5p, and miR-302c-3p ( Cho et al., 2022 ). Apart from these findings, it is noteworthy that WJ-MSCs and their exosomes are the most attractive source of stem cells when immunosuppression is needed in inflammatory or infectious conditions ( Drobiova et al., 2023 ). Research suggests that TLR3 and TLR4 ligation may cause a pro-inflammatory phenotype in bone marrow (BM)- and adipose (AD)-MSCs.…”

A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome

“…Several proteomic studies have been performed to clarify the composition of the secretome of MSCs [ 580 , 581 , 582 ]. The complex secretome of MSCs consists, among others, of cytokines, chemokines, growth factors, extracellular matrix components, and extracellular vesicles [ 379 , 413 , 434 , 439 , 463 , 491 , 555 , 580 , 583 , 584 , 585 , 586 , 587 , 588 , 589 , 590 , 591 , 592 , 593 , 594 ] ( Table 5 , Figure 1 and Figure 2 , and Supplementary Figure S1 ). Some of these factors are expressed in sub-population of MSCs, and their expression levels can be affected by interaction with other cell types, by cytokines, and by hypoxia [ 424 , 595 , 596 , 597 , 598 , 599 , 600 ].…”