Novel Immunomodulatory Markers Expressed by Human WJ-MSC: an Updated Review in Regenerative and Reparative Medicine

Abstract

Mesenchymal (stromal) stem cells (MSC) are a broad class of stromal populations which are able to differentiate towards mature cell types, and do express molecules involved in immune modulation, tolerance induction and inflammation dampening. MSC can be virtually isolated from each adult organ, as well as from foetus-associated perinatal tissues. In particular, Wharton's jelly-derived MSC (WJ-MSC) bear all of these key properties, together with their ease of sourcing and lack of ethical issues.Cellular therapy is a key technique in regenerative medicine approaches, in particular for the treatment of diseases in which physiological processes of cellular repopulation are blocked by the underlying pathological conditions. Recent data enlightened the ability of administered cells to act also in a repopulation-independent fashion in target organs, since their peculiar immunomodulatory and anti-inflammatory features may favor organ self-repair by reactivating local progenitors by both cell-mediated or paracrine mechanisms. Translating classical regenerative medicine to "reparative medicine" or "support medicine" should represent a further therapeutic strategy independent from the differentiation capacity of MSC populations.Recent data further highlighted that WJ-MSC outperform BM-MSC (which are now being applied clinically) both in terms of immune modulation and lack of tumorigenesis (or tumor-promoting activities) in vivo. Starting from these premises, this paper analyzes the recent data on the biology of WJ-MSC, considering the role of both naïve and differentiated cells in immune modulation. In particular, the role of tolerance promoting pathways via non-classical B7 costimulators or class Ib MHC molecules are examined. In addition, we also analyzed the interconnections with other mechanicistic pathways (as those driven by matrix degrading metalloproteinases) in immune modulation. Our observations strongly support the notion that WJ-MSC may constitute a new tool in regenerative and reparative medicine applications.

Human Wharton's Jelly Mesenchymal Stem Cells Maintain the Expression of Key Immunomodulatory Molecules When Subjected to Osteogenic, Adipogenic and Chondrogenic Differentiation In Vitro: New Perspectives for Cellular Therapy

“…T-cell anergy is mechanism by which MSCs induce immunosuppression: some authors demonstrated that the lack expression of two co-stimulatory molecules such as CD80 (B7-1) and CD86 (B7-2) by MSCs could induce an anergy state in T cells [68]. In our report, we showed by immunohistochemistry analysis that both undifferentiated and differentiated WJ-MSCs do not express the two B7 molecules.…”

New Frontiers in Regenerative Medicine in Cardiology: The Potential of Wharton’s Jelly Mesenchymal Stem Cells

“…As summarized by Pourrajab and co-workers, it was also supposed that the mechanisms by which BM-MSCs can reach the site of injury and exert their regulation in cardioprotection is related to the modification of extracellular matrix (ECM) under the stressed cardiac cells releasing of proteinases, such as metalloproteinases (MMPs), on the different collagen molecules [60]. MMPs constitute a broad family of extracellular proteinases which are involved in the development, function and pathogensis of several tissues and organs [62][63][64] as well as in immunomodulation by mesenchymal stem cells (reviewd in [65]). ECM fragments seem to be involved in BM-MSCs chemotaxis and were also associated to the subsequent downregulation of collagen synthesis by resident cardiac fibroblasts [60].…”

Recent Advances in Derivation of Functional Hepatocytes from Placental Stem Cells

“…Another recent report on the use of MSCs in alleviating fibrosis showed that exosomes, released by human umbilical cord MSCs, reduced liver fibrosis, inflammation and collagen deposition in CCl4-induced fibrosis [32]. In addition, also matrix metalloproteinases, which have multiple roles in physiology and pathophysiology [33][34][35], have been suggested as key players in overcoming fibrosis effects [36].…”

“…Several reports indicate that MSCs express non classical type I HLAs such as HLA-G (as well as its soluble form HLA-G5) [60,63,64], HLA-F and HLA-E [36]. To date, HLA-E expression has been observed in BM-MSC and WJMSCs, as well as in heart-resident MSCs [36,[65][66][67][68].…”

“…To date, HLA-E expression has been observed in BM-MSC and WJMSCs, as well as in heart-resident MSCs [36,[65][66][67][68]. It has been also demonstrated that these class Ib MHC molecules are involved in the instauration of tolerance of the mother's immune system toward the semi-allogeneic embryo and in the induction of tolerance of NK cells toward self cells [69,70], acting coordinately with other key molecules as Early Pregnancy Factor [71,72].…”