No abstract

Umbilical cord (UC) is a discarded product from the operating theatre and a ready source of mesenchymal stromal cells (MSCs). MSCs from UC express both embryonic and adult mesenchymal stem cell markers and are known to be hypoimmunogenic and non-tumorigenic and thus suitable for allogeneic cell transplantation. Our study aimed to determine the degree of immunotolerance and bone-forming capacity of osteodifferentiated human Wharton's jelly-derived mesenchymal stromal cells (hWJ-MSCs) from different segments of UC in an allogenic setting. UCs were obtained from healthy donors delivering a full-term infant by elective Caesarean section. hWJ-MSCs were isolated from 3 cm length segment from the maternal and foetal ends of UCs. Three-dimensional fibrin constructs were formed and implanted intramuscularly into immunocompetent mice. The mice were implanted with 1) fibrin construct with maternal hWJ-MSCs, 2) fibrin construct with foetal hWJ-MSCs, or 3) fibrin without cells; the control group received sham surgery. After 1 month, the lymphoid organs were analysed to determine the degree of immune rejection and bone constructs were analysed to determine the amount of bone formed. A pronounced immune reaction was noted in the fibrin group. The maternal segment constructs demonstrated greater osteogenesis than the foetal segment constructs. Both maternal and foetal segment constructs caused minimal immune reaction and thus appear to be safe for allogeneic bone transplant. The suppression of inflammation may be a result of increased anti-inflammatory cytokine production mediated by the hWJ-MSC. In summary, this study demonstrates the feasibility of using bone constructs derived from hWJ-MSCs in an allogenic setting.

No abstract

Supplementation of the progestogen, dydrogesterone, in the first trimester to primigravidae has shown great potential in reducing or preventing the incidence of gestational hypertension.

Mesenchymal stem cells (MSCs) are multipotent progenitor cells that are reported to be immune-privileged and immune-evasive. MSCs are capable of differentiating into specific cell types for subsequent use in cell-based therapy. They express low levels of human leucocyte antigen (HLA)-ABC and no HLA-DR. Wharton’s jelly-derived MSCs (WJ-MSCs) were also found to express human leukocyte antigen G (HLA-G), which renders them immunosuppressive. This study aimed to determine whether cultured WJ-MSCs retain their immune-privileged and immune-evasive properties after cell differentiation, and whether these properties differ among MSCs derived from different anatomical segments of the umbilical cord. Umbilical cords of healthy pregnant mothers undergoing caesarean section were obtained and grouped by three anatomical segments: fetal, middle, and maternal segments. WJ-MSCs were isolated, culture-expanded, and differentiated into osteogenic cells. Expression of HLA-DR, HLA-ABC, and HLA-G were quantified using flow cytometry. Both undifferentiated and osteodifferentiated WJ-MSCs were subsequently co-cultured with allogeneic peripheral blood mononuclear cells with/without lipopolysaccharide (LPS) stimulation for five days. Lymphocyte proliferation assay was performed using carboxyfluorescein succinimidyl ester (CFSE) as a tracker. Our results showed no significant difference existed in the HLA profiles among WJ-MSCs from different segments and between WJ-MSCs with and without osteogenic differentiation. Mean levels for HLA-G, HLABC, and HLA-DR were 24.82±17.64, 52.50±18.41, and 1.00±1.68%, respectively. Stimulation with LPS and WJ-MSCs increased peripheral blooc mononuclear cells (PBMC) proliferation. However, PBMC proliferation was significantly lower when PBMCs were co-cultured with osteodifferentiated WJ-MSCs (p < .05; with LPS stimulation and p < .001 without LPS stimulation) than when they were co-cultured with undifferentiated WJ-MSCs. These findings suggest that cultured WJ-MSCs stimulate lymphocyte proliferation and are not immune-privileged. Osteodifferentiated WJ-MSCs reduced the immunogenicity of WJ-MSCs, and this reduction in PBMC proliferation was even more pronounced in the presence of LPS (p < .05). In conclusion, cultured WJ-MSCs are not immune-privileged. Osteodifferentiated WJ-MSCs are less immunogenic than undifferentiated WJ-MSCs, in which case hypoimmunogenicity is more profound under LPS-stimulated conditions.