Publications (2)1.55 Total impact
- [Show abstract] [Hide abstract]
ABSTRACT: Objective To compare the immunosuppressive effects of maternal and fetal placental mesenchymal stem cells (mPMSCs and fPMSCs, respectively) on the rejection of allogenic skin transplants in mice, and further to investigate the mechanism underlying this suppression. Methods The mPMSCs and fPMSCs were isolated from human term placentas. The expressions of cell surface markers were detected by flow cytometry. Cell proliferation capacity was characterized by MTT colorimetric assay. CD200 protein expressed on fPMSCs was neutralized with streaming monoclonal antibodies, and mPMSCs were infected with adenovirus expression vector carrying CD200 cDNA. For skin transplantation, 60 C57BL/6 mice were randomly divided into 6 groups as skin transplant recipients, and ICR mice served as skin donors. After establishment of the allogenic skin transplants, recipient mice of the 6 groups were intravenous injected respectively with PBS, mPMSCs, fPMSCs, fPMSCs combined with anti-CD200 antibodies, mPMSCs with CD200 expressing vectors, and mPMSCs with empty vectors. The conditions and survival time of the skin grafts were inspected daily, and the expressions of interleukin 17 (IL-17), interferon γ (IFN-γ), tumor necrosis factor α (TNF-α) and interleukin 12 (IL-12) in blood and spleen were measured at the end of the study by ELISA and reverse transcription PCR. Results The majority (>70%) of fPMSCs were detected CD200 positive, while only a minor fraction (about 2%) of CD-200 positive cells were seen in mPMSCs. In the allogenic skin graft mice, the graft survival time in both mPMSCs- and fPMSCs-treated groups were significantly longer than that in PBS group [(5.6±1.17) days], while the fPMSCs group [(10.6±1.43) days] was more dominant than mPMSCs group [(7.7±1.42) days]. Neutralizing anti-CD200 antibody reduced the graft survival [(8.2±1.14) days] of the fPMSCs group to the level of that in mPMSCs group, while enforced expression of CD200 increased the graft survival [(10.7±1.34) days] of the mPMSCs group to the level of the fPMSCs group. The empty vector-transfected mPMSCs showed a similar effect on graft survival [(7.8±1.32) days] as that in mPMSCs group, longer than PBS group but shorter than fPMSCs and mPMSCs combined with CD200 groups. Comparing with PBS group, the expressions of IL-17, IFN-γ and TNF-α were significantly reduced in mPMSCs and fPMSCs groups. The reduction of these cytokine expressions in the fPMSCs group was neutralized when anti-CD200 antibody was applied, while this reduction in the mPMSCs-treated mice was further enhanced when the mPMSCs were enforced to express CD200. Conclusion The immunosuppressive effect of fPMSCs on the rejection of allogenic skin transplantation was higher than that of mPMSCs, and this difference was partially contributed by CD200 signaling pathway. The mechanism of this suppression may mediate the inhibition of IL-17, IFN-γ, TNF-α and IL-12 expressions. The fPMSCs may be a suitable choice for immunosuppression on skin transplantation.
- [Show abstract] [Hide abstract]
ABSTRACT: Human placenta-derived mesenchymal stem cells (P-MSCs) have drawn increasing attention in the field of stem cell research due to their potential in clinical applications as well as their rich and easy to procure cell source. While studies demonstrating the potential of P-MSCs for therapeutic transplantations have been documented, a clinically compliant procedure for P-MSC expansion in vitro has yet to be established. To this end, previous studies have demonstrated that MSCs of bone marrow and cord blood origins cultured in human cord blood serum (hCBS) are comparable to those cultured in fetal bovine serum (FBS), indicating that hCBS may be an alternative to FBS for the development of in vitro cell expansion procedures free of animal components. However, stem cells from origins other than bone marrow or cord blood, particularly from human placental tissues, which have demonstrated a good potential for clinical applications, have not been characterized under similar conditions. In this study, in an attempt to define a clinically compliant protocol for P-MSC expansion in vitro, we examined the effects of human hCBS as a replacement for FBS on cell proliferation capacity, differentiation potential, MSC-specific phenotypic expression and the genetic stability of P-MSCs in cultures. P-MSCs expanded in vitro in autologous hCBS maintained the capacity of self‑renewal and expressed surface antigens characteristic of bone marrow-derived mesenchymal stem cells. Under differentiation conditions, the P-MSCs expanded in hCBS developed into adipogenic, osteogenic and neurogenic cell phenotypes. Chromosomal karyotyping and single cell gel electrophoresis analysis demonstrated that P-MSCs cultured in autologous hCBS were genetically stable. These results suggest that autologous hCBS may be used as an alternative to FBS for the in vitro expansion of P-MSCs for clinical applications.
Ningxia Medical UniversityNing-hsia, Ningxia Huizu Zizhiqu, China