Are the Immune Properties of Mesenchymal Stem Cells from Wharton’s Jelly Maintained during Chondrogenic Differentiation?

Abstract

Background: Umbilical mesenchymal stem/stromal cells (MSCs), and especially those derived from Wharton’s jelly (WJ), are a promising engineering tool for tissue repair in an allogeneic context. This is due to their differentiation capacity and immunological properties, like their immunomodulatory potential and paracrine activity. Hence, these cells may be considered an Advanced Therapy Medicinal Product (ATMP). The purpose of this work was to differentiate MSCs from WJ (WJ-MSCs) into chondrocytes using a scaffold and to evaluate, in vitro, the immunomodulatory capacities of WJ-MSCs in an allogeneic and inflammatory context, mimicked by IFN-γ and TNF-α priming during the chondrogenic differentiation. Methods: Scaffolds were made from hydrogel composed by alginate enriched in hyaluronic acid (Alg/HA). Chondrogenic differentiation, immunological function, phenotype expression, but also secreted soluble factors were the different parameters followed during 28 days of culture. Results: During chondrocyte differentiation, even in an allogeneic context, WJ-MSCs remained unable to establish the immunological synapse or to induce T cell alloproliferation. Moreover, interestingly, paracrine activity and functional immunomodulation were maintained during cell differentiation. Conclusion: These results show that WJ-MSCs remained hypoimmunogenic and retained immunomodulatory properties even when they had undergone chondrocyte differentiation.

Melatonin Synergizes With Mesenchymal Stromal Cells Attenuates Chronic Allograft Vasculopathy

“…Mesenchymal stromal cells (MSCs) are considered as “immune privileged cells” due to low expression of MHC-II as well as the absence of costimulatory molecules such as B7-1, B7-2, CD40, and CD40L on the cell surface ( 17 , 18 ). They have been proposed as the promising “live” drugs being able to target the anti-donor immune response and prolong allograft survival in human and rodent studies, which may offer new insights for the prevention of CAV ( 19 – 21 ).…”

Mesenchymal Stem/Stromal Cells in Immunity and Disease: A Better Understanding for an Improved Use

“…Buyl, K. et al pointed out the responses and characteristics of MSCs from adipose tissue, following expansion and inflammatory priming that substantially modulated the expression of 28 molecules implicated in immune regulation [5]. Consequently, Voisin, C. et al indicated that MSCs from the umbilical cord remained hypoimmunogenic, and retained their immunomodulatory properties during chondrocyte differentiation [6]. Further, Elango, J. et al noted that the parathyroid hormone-related protein (PTHrP) shows accelerated soluble receptor activator of nuclear factor (NF)-kB ligand (sRANKL) downregulation of osteogenesis of MSCs, by increasing RANK expression at the earlier stage of differentiation and by inhibiting ANK [7].…”

Macrophage migration inhibitory factor facilitates the therapeutic efficacy of mesenchymal stem cells derived exosomes in acute myocardial infarction through upregulating miR-133a-3p

“…through paracrine factors such as exosomes. [20][21][22][23] Recent studies have shown that exosomes derived from MSCs reduce myocardial ischemic injury and preserve cardiac function after MI. 24,25 Compared with conventional stem cell transplantation therapy, exosome therapy showed no teratoma development, minimum immunogenicity, and little potential for tumorigenesis.…”