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Immunomodulatory properties of Wharton’s jelly-derived mesenchymal stem cells from three anatomical segments of umbilical cord
Lim, Jezamine1, Sue, Ping Eng2, Yeoh, Wei Yen3, Low, Yik Wan4, Nur Mohd Shafwan Jusoh5, Ain Syahirah Rahmat6, Amirah Shahrani7, Faiq Bahrani Yahya8, Rushda Adiba Abdul Rahman9, Zainul Rashid Mohamad Razi10, Leong, Chooi Fun11, Jose, Shinsmon12, Min, Hwei Ng13.
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.
Affiliation:
- Universiti Kebangsaan Malaysia Medical Centre, Malaysia
- Universiti Kebangsaan Malaysia Medical Centre, Malaysia
- Universiti Kebangsaan Malaysia Medical Centre, Malaysia
- Universiti Kebangsaan Malaysia Medical Centre, Malaysia
- Universiti Kebangsaan Malaysia Medical Centre, Malaysia
- Universiti Kebangsaan Malaysia Medical Centre, Malaysia
- Universiti Kebangsaan Malaysia Medical Centre, Malaysia
- Universiti Kebangsaan Malaysia Medical Centre, Malaysia
- Universiti Kebangsaan Malaysia Medical Centre, Malaysia
- Universiti Kebangsaan Malaysia Medical Centre, Malaysia
- Universiti Kebangsaan Malaysia Medical Centre, Malaysia
- Universiti Kebangsaan Malaysia Medical Centre, Malaysia
- Universiti Kebangsaan Malaysia Medical Centre, Malaysia
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Indexation |
Indexed by |
MyJurnal (2021) |
H-Index
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6 |
Immediacy Index
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0.000 |
Rank |
0 |
Indexed by |
Web of Science (SCIE - Science Citation Index Expanded) |
Impact Factor
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JCR (1.009) |
Rank |
Q4 (Multidisciplinary Sciences) |
Additional Information |
JCI (0.15) |
Indexed by |
Scopus 2020 |
Impact Factor
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CiteScore (1.4) |
Rank |
Q2 (Multidisciplinary) |
Additional Information |
SJR (0.251) |
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