Cell membrane and bioactive factors derived from mesenchymal stromal cells: Cell-free based therapy for inflammatory bowel diseases

Abstract

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract associated with multifactorial conditions such as ulcerative colitis and Crohn's disease. Although the underlying mechanisms of IBD remain unclear, growing evidence has shown that dysregulated immune system reactions in genetically susceptible individuals contribute to mucosal inflammation. However, conventional treatments have been effective in inducing remission of IBD but not in preventing the relapse of them. In this way, mesenchymal stromal cells (MSC) therapy has been recognized as a promising treatment for IBD due to their immunomodulatory properties, ability to differentiate into several tissues, and homing to inflammatory sites. Even so, literature is conflicted regarding the location and persistence of MSC in the body after transplantation. For this reason, recent studies have focused on the paracrine effect of the biofactors secreted by MSC, especially in relation to the immunomodulatory potential of soluble factors (cytokines, chemokines, and growth factors) and extracellular vehicles that are involved in cell communication and in the transfer of cellular material, such as proteins, lipids, and nucleic acids. Moreover, treatment with interferon-γ, tumor necrosis factor-α, and interleukin-1β causes MSC to express immunomodulatory molecules that mediate the suppression via cell-contact dependent mechanisms. Taken together, we present an overview of the role of bioactive factors and cell membrane proteins derived from MSC as a cell-free therapy that can improve IBD treatment.

Stem Cell Membrane‐Coated Microribbon Scaffolds Induce Regenerative Innate and Adaptive Immune Responses in a Critical‐Size Cranial Bone Defect Model

“…PD‐L1 and TNFL6 are two well‐known immunomodulatory ligands on MSCs that are known to inhibit adaptive T cell immune response through cell‐cell contact. [ 18,28 ] We first confirmed the presence of PD‐L1 and TNFL6 on intact MSCs using flow cytometry (Figure 1d). Consistent with our hypothesis, IFN‐γ priming significantly increased the expression level of PD‐L1 and TNFL6, compared to naïve MSCs.…”

The Enigmatic Regulators of Central Nervous System Diseases- Extracellular Vesicles Derived from Mesenchymal Stem Cell

“…Recent studies have shown that MSC-EVs can improve the recovery of damaged tissues [84], and identified 730 proteins by LC coupled MS/MS analysis, 43 surface receptors as well as signaling molecules are characterized, which is responsible for self-renewal and differentiation. Some other analysis indicated that MSCs-EVs proteins contributed to cell proliferation, migration, adhesion, and morphogenesis [88,89]. Self-renewal ability and differentiation potentiality of MSCs can be associated with the therapeutic effects, which is regulated by the integration of related genes, including signaling molecules (CDC42, VAV2); surface receptors (PDGFRB, EGFR, and PLAUR); antigens (CD109, CD248, CD151 and CD276) [84].…”

Colon-targeted EMSCs conditional medium hydrogel for treatment of ulcerative colitis in mice

“…However, their poor post-transplant cell survival rate, complications, and other ethical issues hinder clinical application [11,12]. Recent studies reported that the efficacy of MSCs is mainly attributed to their paracrine action on the improvement of the local microenvironment [13][14][15]. Previous findings also indicated that ecto-mesenchymal stem cells-conditional medium (EMSCs-CM) with potent anti-inflammation potential has therapeutic effects on colitis [16].…”