1.Influence of adult bone marrow mesenchymal stem cells on solid organ transplantation: Significant candidate cells during tolerance induction
Chinese Journal of Tissue Engineering Research 2010;14(1):147-151
BACKGROUND: Mesenchymal stem cells (MSCs) from adult bone marrow can alter alloimmune response in vitro and vivo. Their potentiality is great in solid organ transplantation.OBJECTIVE: To develop MSC antirejection therapy and identify behind mechanishm of MSCs immunomodulation ability. METHODS: We searched Pubmed (1994-Mar.2009) with the key words of "mesenchymal stem cells, solid organ transplantation, tolerance, immunosuppression, animal model". RESULTS AND CONCLUSION: Totally 262 English articles about influence and mechanism of action of adult bone marrow mesenchymal stem cells on solid organ transplantation were collected. The 49 suitable articles were included without earlier publication time, repeated and analogous study. Human mesenchymal stem cells did not express MHC2 Ⅱ antigen and T cell costimulatory molecules B7. Coculture with allogenic T lymphocytes could not induce T cell proliferation, but inhibited mixed lymphocyte reaction and mitogenstimulated T cell proliferation. Inhibitory effects of mesenchymal stem cells on T cell proliferation were not limited by major histocompatibility complex. Mesenchymal stem cells no matter from donors or recipients had similar immunoloregulation effects. Allogene mesenchymal stem cells could cause immunereaction in vivo, no complete immune privilege. The in vivo effects of mesenchymal stem cells will strongly depend on their localization and migration pattern after injection. Therefore, MSCs are interesting candidate cells for tolerance induction in clinical organ transplantation.
2.Isolation and biological characteristics of rat umbilical cord mesenchymal stem cells
Kuili LIU ; Bingyi SHI ; Dezhong LIU ; Jiangang JIN ; Haibin LI ; Yingchang SHI ; Kai FENG ; Li XIAO
Chinese Journal of Tissue Engineering Research 2010;14(10):1743-1748
BACKGROUND:There are many studies concerning rat bone marrow mesenchymal stem cells for immune tolerance following transplantation and tissue repair.However,there are no reports on umbilical cord mesenchymal stem cells(UCMSCs).OBJECTIVE:To establish a method of separating mesenchymal stem cells(MSCs)from rat umbilical cord,and to study its biological characteristics.METHODS:MSCs were separated from rat umbilical cord with enzyme method and tissue mass method,and then incubated in DMEM-LG medium.Cell morphology was observed under an inverted microscope.Growth curves of cells were drawn using cell counting.Cell cycle and surface antigen were detected with flow cytometry.Adipogenic differentiation and osteogenic differentiation were tested by immunohistochemistry.RESULTS AND CONCLUSION:Both of the two methods could obtain plenty of MSCs from rat umbilical cord.Primary culture showed that the efficiency of enzyme method was higher than tissue mass method.Passage time of the former was about 10 days and the latter was 14 days.The passage time of latter except primary culture was the same.Immunophenotype analysis showed that MSCs from rat umbilical cord expressed adhesion molecule and stromal cell markers,CD90 and CD106,but did not express hematopoietic cell markers,CD34 and CD45.In vitro induction test verified that rat UCMSCs have the potentials of adipogenic and osteogenic differentiation.
3.Immunomodulatory effects of xenogenous umbilical cord mesenchymal stem cells on rat heart transplantation
Kuili LIU ; Dezhong LIU ; Jiangang JIN ; Haibin LI ; Yingchang SHI ; Li LI ; Yong HAN ; Xiaoguang XU ; Bingyi SHI
Chinese Journal of Tissue Engineering Research 2010;14(6):1048-1052
BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) can prolong the survival time of mice and baboons' alloskin graft and degrade acute and chronic graft-versus-host disease (GVHD) incidence after hematopoietic stem cell transplantation. But, at present there is no report that rat umbilical cord mesenchymal stem cells (UC-MSCs) reduced rejection response following heart transplantation. OBJECTIVE: To study the immunomodulatory effects of rat UC-MSCs on a model of allogeneic heart transplantation. METHODS: A total of 20 DA rats served as donors, and 20 Lewis rats as recipients. They were equally and randomly assigned to 2 groups: drug intervention and control groups (n=10). Using double cannulation, the left pulmonary artery and innominate artery of rat donors and external jugular vein and common carotid artery of rat recipients received end-to-end anastomosis under a microscope to establish heterotopic cardiac transplantation. One Wistar pregnant rat was selected to harvest UC-MSCs by collagenase digestion method. Following model establishment, rats in the cell transplantation group received UC-MSCs via caudal vein. Rats in the control group received sodium chloride. Survival time of the transplanted heart was determined. The transplanted heart received histopathology score using the acute rejection diagnosis criteria. Lymphocyte infiltration of transplanted heart was observed using hematoxylin-eosin staining. RESULTS AND CONCLUSION: Compared with the control group, the survival time of the transplanted heart was significantly longer in the cell transplantation group (P = 0.001), and the pathological score of acute rejection was significantly reduced (P = 0.000 4). There were lots of lymphocyte and monocyte infiltration in the myocardium in the control group. Little lymphocyte infiltration was detected in the myocardium in the cell transplantation group, with the presence of mild edema of myocardial interstitial substance. Results verified that rat UC-MSCs can induce immune tolerance of heart transplantation, soften immunological rejection and prolong xenograft survival.
4.Rnf20 deficiency in adipocyte impairs adipose tissue development and thermogenesis.
Xiaojuan LIANG ; Cong TAO ; Jianfei PAN ; Lilan ZHANG ; Lulu LIU ; Ying ZHAO ; Yiping FAN ; Chunwei CAO ; Jiali LIU ; Jin ZHANG ; Sin Man LAM ; Guanghou SHUI ; Wanzhu JIN ; Wei LI ; Jianguo ZHAO ; Kui LI ; Yanfang WANG
Protein & Cell 2021;12(6):475-492
RNF20, an E3 ligase critical for monoubiquitination of histone H2B at lysine 120 (H2Bub), has been implicated in the regulation of various cellar processes; however, its physiological roles in adipocytes remain poorly characterized. Here, we report that the adipocyte-specific knockout of Rnf20 (ASKO) in mice led to progressive fat loss, organomegaly and hyperinsulinemia. Despite signs of hyperinsulinemia, normal insulin sensitivity and improved glucose tolerance were observed in the young and aged CD-fed ASKO mice. In addition, high-fat diet-fed ASKO mice developed severe liver steatosis. Moreover, we observed that the ASKO mice were extremely sensitive to a cold environment due to decreased expression levels of brown adipose tissue (BAT) selective genes, including uncoupling protein 1 (Ucp1), and impaired mitochondrial functions. Significantly decreased levels of peroxisome proliferator-activated receptor gamma (Pparγ) were observed in the gonadal white adipose tissues (gWAT) from the ASKO mice, suggesting that Rnf20 regulates adipogenesis, at least in part, through Pparγ. Rosiglitazone-treated ASKO mice exhibited increased fat mass compared to that of the non-treated ASKO mice. Collectively, our results illustrate the critical role of RNF20 in control of white and brown adipose tissue development and physiological function.