Immune Properties of Human Umbilical Cord Wharton's Jelly-Derived Cells

Abstract

Cells isolated from Wharton's jelly, referred to as umbilical cord matrix stromal (UCMS) cells, adhere to a tissue-culture plastic substrate, express mesenchymal stromal cell (MSC) surface markers, self-renew, and are multipotent (differentiate into bone, fat, cartilage, etc.) in vitro. These properties support the notion that UCMS cells are a member of the MSC family. Here, the immune properties of UCMS cells are characterized in vitro. The overall hypothesis is that UCMS cells possess immune properties that would be permissive to allogeneic transplantation. For example, UCMS cells will suppress of the proliferation of "stimulated" lymphocytes (immune suppression) and have reduced immunogenicity (e.g., would be poor stimulators of allogeneic lymphocyte proliferation). Hypothesis testing was as follows: first, the effect on proliferation of coculture of mitotically inactivated human UCMS cells with concanavalin-A-stimulated rat splenocytes was assessed in three different assays. Second, the effect of human UCMS cells on one-way and two-way mixed lymphocyte reaction (MLR) assays was determined. Third, the expression of human leukocyte antigen (HLA)-G was examined in human UCMS cells using reverse transcription-polymerase chain reaction, since HLA-G expression conveys immune regulatory properties at the maternal-fetal interface. Fourth, the expression of CD40, CD80, and CD86 was determined by flow cytometry. Fifth, the cytokine expression of UCMS cells was evaluated by focused gene array. The results indicate that human UCMS cells inhibit splenocyte proliferation response to concanavalin A stimulation, that they do not stimulate T-cell proliferation in a one-way MLR, and that they inhibit the proliferation of stimulated T cells in a two-way MLR. Human UCMS cells do not inhibit nonstimulated splenocyte proliferation, suggesting specificity of the response. UCMS cells express mRNA for pan-HLA-G. UCMS cells do not express the costimulatory surface antigens CD40, CD80, and CD86. UCMS cells express vascular endothelial growth factor and interleukin-6, molecules previously implicated in the immune modulation observed in MSCs. In addition, the array data indicate that UCMS cells make a cytokine and other factors that may support hematopoiesis. Together, these results support previous observations made following xenotransplantation; for example, there was no evidence of frank immune rejection of undifferentiated UCMS cells. The results suggest that human UCMS will be tolerated in allogeneic transplantation.

Isolation of Mesenchymal Stem Cells from Wharton’s Jelly in Comparison with Bone Marrow and Their Endothelial Differentiation

“…These results were in agreement with Li et al, [24]. The differences between adult-derived MSCs and UC-MSCs are that UC-MSCs have the potential for faster expansion ex vivo, and UC-MSCs have telomerase activity and the umbilical cord is relatively enriched for CFU-F compared with bone marrow [26].…”

Umbilical cord-derived stem cells (ModulatistTM) show strong immunomodulation capacity compared to adipose tissue-derived or bone marrow-derived mesenchymal stem cells

“…This also means that Modulatists are a heterogenous MSC population that exhibits properties of both UCMSCs and Wharton's jelly-derived MSCs (WJMSCs). As suggested in some previous studies, both UCMSCs and WJMSCs are great prototypes of MSCs with strong immune modulation and low immunogenicity (Barcia et al, 2015;Li et al, 2014;Weiss et al, 2008). Barcia et al (2015) demonstrated that UCMSCs were less immunogenic and showed higher immunosuppressive activity than BMMSCs (Barcia et al, 2015).…”

“…In fact, Barcia et al showed that UCMSCs, compared to BMMSCs, show decreased expression of HLA-DRA, HO-1, IGFBP-1, -4 and -6, ILR1, IL6R, and PTGES; however, they show increased expression of CD200, CD273, CD274, IL1B, IL-8, LIF and TGFB2 (Barcia et al, 2015). WJMSCs are also a great source of MSCs; several previous publications have shown that WJMSCs exert strong suppression on lymphocyte proliferation and have low immunogenicity (Weiss et al, 2008;Zhou et al, 2011). In a recent study by , the immune modulation of 4 cell populations (BMMSCs, ADSCs, placenta-derived MSCs and WJMSCs) were compared .…”

Transplantation of umbilical cord–derived mesenchymal stem cells as a novel strategy to protect the central nervous system: technical aspects, preclinical studies, and clinical perspectives

“…Thus, they display immune-privilege properties (52)(53)(54)(55), have been shown to be well tolerated in allogeneic transplantation experiments (56,57), and can be differentiated into cells of mesodermal origin such as bone, cartilage, and adipose tissue (58). Moreover, hUC-MSCs cultured in neural induction medium develop neural morphologies and express neural markers such as Nestin, glial fibrillary acidic protein, and NeuN (5,46,59,60), suggesting that they have great potential for cell-based therapies in the context of central nervous system diseases.…”