间充质干细胞在器官移植中的应用研究进展

曲泽澎; 贾兆锋; 黄曦; 蔡志明; 牟丽莎

doi:10.3969/j.issn.1674-7445.2018.05.005

间充质干细胞在器官移植中的应用研究进展

doi: 10.3969/j.issn.1674-7445.2018.05.005

510275　广州，中山大学中山医学院（曲泽澎、黄曦、牟丽莎）；深圳市第二人民医院（曲泽澎、贾兆锋、蔡志明、牟丽莎）

基金项目:

国家重点研发计划 2017YFC1103704

深圳市医疗卫生三名工程 SZSM201412020

深圳市医学高水平学科建设 2016031638

深圳市科技计划 JCJY20160229204849975

深圳市科技计划 GJHZ20170314171357556

深圳市科技计划 JCYJ20170818103626421

深圳市卫生计生系统科研项目 SZXJ2017021

深圳市卫生计生系统科研项目 SZXJ2018059

详细信息

作者简介:
曲泽澎, 男, 1983年生, 博士, 助理研究员, 研究方向为MSC在异种胰岛移植中的应用, Email:zepengqu@gmail.com

牟丽莎, 深圳市高层次领军人才, 博士后合作导师。现任中华医学会器官移植学分会第七届委员会异种移植学组委员, 国家自然科学基金、广东省自然科学基金、深圳市科技评审专家。兼任《器官移植》杂志通讯编委。主持参与各级科研项目10余项, 其中主持国家重点研发计划子课题1项、国家自然科学基金1项、广东省自然科学基金1项、广东省医学科学基金1项、中国博士后基金1项、深圳市学科布局项目1项、深圳市国际合作项目2项、深圳市基础研究计划1项、深圳市科技计划项目1项。在《Cell Research》、《Human Genetics》等杂志上发表SCI论文34篇。成功申请国际和国内发明专利30余项

通讯作者:
牟丽莎, 女, 1983年生, 博士, 副研究员, 研究方向为异种胰岛移植, Email:lishamou@gmail.com

中图分类号: R617, R392.4
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- HTML全文浏览量: 82
- PDF下载量: 19
- 被引次数: 0
出版历程
- 收稿日期: 2018-07-10
- 网络出版日期: 2021-01-19
- 刊出日期: 2018-09-15

Application and research progress on mesenchymal stem cell in organ transplantation

摘要

摘要: 器官移植是终末期器官功能衰竭的有效治疗方法。然而, 移植受体需长期使用免疫抑制剂以降低器官移植免疫排斥反应。间充质干细胞(MSC)具有独特的免疫学特性, 有望在器官移植中发挥重要作用。本文总结了MSC的免疫学特性, 并就其在器官移植中减轻免疫排斥反应、诱导免疫耐受、促进组织修复、诱导新生血管形成以及在异种器官移植中的作用等方面的研究进展进行了简述, 以期为MSC应用于器官移植提供参考。
- 间充质干细胞 /
- 器官移植 /
- 移植免疫 /
- 免疫调节 /
- 免疫耐受 /
- 新生血管 /
- 异种器官移植

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参考文献(37)

[1]	ZANGI L, MARGALIT R, REICH-ZELIGER S, et al.Direct imaging of immune rejection and memory induction by allogeneic mesenchymal stromal cells[J].Stem Cells, 2009, 27(11):2865-2874.DOI: 10.1002/stem.217.
[2]	SCHMUCK EG, KOCH JM, CENTANNI JM, et al.Biodistribution and clearance of human mesenchymal stem cells by quantitative three-dimensional cryo-imaging after intravenous infusion in a rat lung injury model[J].Stem Cells Transl Med, 2016, 5(12):1668-1675. doi: 10.5966/sctm.2015-0379
[3]	BARTHOLOMEW A, STURGEON C, SIATSKAS M, et al.Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo[J].Exp Hematol, 2002, 30(1):42-48. doi: 10.1016/S0301-472X(01)00769-X
[4]	WU SM, ZHANG WX, WANG MH, et al.Proteomic analysis of the immunosuppressive effects of mesenchymal stem cells in a rat heart transplantation model[J].Adv Clin Exp Med, 2013, 22(6):785-794. https://www.ncbi.nlm.nih.gov/pubmed/24431306
[5]	WANG Y, CHEN X, CAO W, et al.Plasticity of mesenchymal stem cells in immunomodulation:pathological and therapeutic implications[J].Nat Immunol, 2014, 15(11):1009-1016.DOI: 10.1038/ni.3002.
[6]	BARHANPURKAR-NAIK A, MHASKE ST, POTE ST, et al.Interleukin-3 enhances the migration of human mesenchymal stem cells by regulating expression of CXCR4[J].Stem Cell Res Ther, 2017, 8(1):168.DOI: 10.1186/s13287-017-0618-y.
[7]	TEO GS, YANG Z, CARMAN CV, et al.Intravital imaging of mesenchymal stem cell trafficking and association with platelets and neutrophils[J].Stem Cells, 2015, 33(1):265-277.DOI: 10.1002/stem.1848.
[8]	PAN GH, CHEN Z, XU L, et al.Low-dose tacrolimus combined with donor-derived mesenchymal stem cells after renal transplantation:a prospective, non-randomized study[J].Oncotarget, 2016, 7(11):12089-12101.DOI: 10.18632/oncotarget.7725.
[9]	REN G, ZHANG L, ZHAO X, et al.Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide[J].Cell Stem Cell, 2008, 2(2):141-150.DOI: 10.1016/j.stem.2007.11.014.
[10]	SOARES MA, MASSIE JP, RIFKIN WJ, et al.Ex vivo allotransplantation engineering:delivery of mesenchymal stem cells prolongs rejection-free allograft survival[J].Am J Transplant, 2018, 18(7):1657-1667.DOI: 10.1111/ajt.14668.
[11]	HAN X, YANG Q, LIN L, et al.Interleukin-17 enhances immunosuppression by mesenchymal stem cells[J].Cell Death Differ, 2014, 21(11):1758-1768.DOI: 10.1038/cdd.2014.85.
[12]	BAUER TM, JIGA LP, CHUANG JJ, et al.Studying the immunosuppressive role of indoleamine 2, 3-dioxygenase:tryptophan metabolites suppress rat allogeneic T-cell responses in vitro and in vivo[J].Transpl Int, 2005, 18(1):95-100. doi: 10.1111/tri.2005.18.issue-1
[13]	OH JY, LEE RH, YU JM, et al.Intravenous mesenchymal stem cells prevented rejection of allogeneic corneal transplants by aborting the early inflammatory response[J].Mol Ther, 2012, 20(11):2143-2152.DOI: 10.1038/mt.2012.165.
[14]	KO JH, LEE HJ, JEONG HJ, et al.Mesenchymal stem/stromal cells precondition lung monocytes/macrophages to produce tolerance against allo- and autoimmunity in the eye[J].Proc Natl Acad Sci U S A, 2016, 113(1):158-163.DOI: 10.1073/pnas.1522905113.
[15]	TIAN Y, WANG J, WANG W, et al.Mesenchymal stem cells improve mouse non-heart-beating liver graft survival by inhibiting Kupffer cell apoptosis via TLR4-ERK1/2-Fas/FasL-caspase3 pathway regulation[J].Stem Cell Res Ther, 2016, 7(1):157. doi: 10.1186/s13287-016-0416-y
[16]	WU XQ, YAN TZ, WANG ZW, et al.BM-MSCs-derived microvesicles promote allogeneic kidney graft survival through enhancing micro-146a expression of dendritic cells[J].Immunol Lett, 2017, 191:55-62.DOI: 10.1016/j.imlet.2017.09.010.
[17]	WESTENFELDER C, GOOCH A, HU Z, et al.Durable control of autoimmune diabetes in mice achieved by intraperitoneal transplantation of " neo-islets, " three-dimensional aggregates of allogeneic islet and " mesenchymal stem cells" [J].Stem Cells Transl Med, 2017, 6(7):1631-1643.DOI: 10.1002/sctm.17-0005.
[18]	PLOCK JA, SCHNIDER JT, ZHANG W, et al.Adipose- and bone marrow-derived mesenchymal stem cells prolong graft survival in vascularized composite allotransplantation[J].Transplantation, 2015, 99(9):1765-1773.DOI: 10.1097/TP.0000000000000731.
[19]	OBERMAJER N, POPP FC, SOEDER Y, et al.Conversion of Th17 into IL-17A(neg) regulatory T cells:a novel mechanism in prolonged allograft survival promoted by mesenchymal stem cell-supported minimized immunosuppressive therapy[J].J Immunol, 2014, 193(10):4988-4999.DOI: 10.4049/jimmunol.1401776.
[20]	RAJESHKUMAR B, AGRAWAL P, RASHIGHI M, et al.Mesenchymal stem cells and co-stimulation blockade enhance bone marrow engraftment and induce immunological tolerance[J].Int J Organ Transplant Med, 2015, 6(2):55-60. http://europepmc.org/abstract/MED/26082829
[21]	MUDRABETTU C, KUMAR V, RAKHA A, et al.Safety and efficacy of autologous mesenchymal stromal cells transplantation in patients undergoing living donor kidney transplantation:a pilot study[J].Nephrology (Carlton), 2015, 20(1):25-33.DOI: 10.1111/nep.12338.
[22]	ZHANG B, YIN Y, LAI RC, et al.Mesenchymal stem cells secrete immunologically active exosomes[J].Stem Cells Dev, 2014, 23(11):1233-1244.DOI: 10.1089/scd.2013.0479.
[23]	GREGORINI M, BOSIO F, ROCCA C, et al.Mesenchymal stromal cells reset the scatter factor system and cytokine network in experimental kidney transplantation[J].BMC Immunol, 2014, 15:44.DOI: 10.1186/s12865-014-0044-1.
[24]	MERINO A, RIPOLL E, DE RAMON L, et al.The timing of immunomodulation induced by mesenchymal stromal cells determines the outcome of the graft in experimental renal allotransplantation[J].Cell Transplant, 2017, 26(6):1017-1030.DOI: 10.3727/096368917X695010.
[25]	QI H, CHEN G, HUANG Y, et al.Foxp3-modified bone marrow mesenchymal stem cells promotes liver allograft tolerance through the generation of regulatory T cells in rats[J].J Transl Med, 2015, 13:274.DOI: 10.1186/s12967-015-0638-2.
[26]	JIANG X, LIU C, HAO J, et al.CD4(+)CD25 (+) regulatory T cells are not required for mesenchymal stem cell function in fully MHC-mismatched mouse cardiac transplantation[J].Cell Tissue Res, 2014, 358(2):503-514.DOI: 10.1007/s00441-014-1956-z.
[27]	谭建明, 王萍.间充质干细胞改善实体器官移植效果的临床研究[J/CD].中华细胞与干细胞杂志(电子版), 2016, 6(5): 263-269.DOI: 10.3877/cma.j.issn.2095-1221.2016.05.001. TAN JM, WANG P.Mesenchymal stem cells to improve solid organ transplant outcome: clinical trials[J/CD].Chin J Cell Stem Cell(Electr Edit), 2016, 6(5): 263-269.DOI: 10.3877/cma.j.issn.2095-1221.2016.05.001.
[28]	MONTANARI S, DAYAN V, YANNARELLI G, et al.Mesenchymal stromal cells improve cardiac function and left ventricular remodeling in a heart transplantation model[J].J Heart Lung Transplant, 2015, 34(11):1481-1488.DOI: 10.1016/j.healun.2015.05.008.
[29]	BAULIER E, FAVREAU F, LE CORF A, et al.Amniotic fluid-derived mesenchymal stem cells prevent fibrosis and preserve renal function in a preclinical porcine model of kidney transplantation[J].Stem Cells Transl Med, 2014, 3(7):809-820.DOI: 10.5966/sctm.2013-0186.
[30]	WATANABE T, HOSHIKAWA Y, ISHIBASHI N, et al.Mesenchymal stem cells attenuate ischemia-reperfusion injury after prolonged cold ischemia in a mouse model of lung transplantation:a preliminary study[J].Surg Today, 2017, 47(4):425-431.DOI: 10.1007/s00595-016-1391-8.
[31]	TIAN W, LIU Y, ZHANG B, et al.Infusion of mesenchymal stem cells protects lung transplants from cold ischemia-reperfusion injury in mice[J].Lung, 2015, 193(1):85-95.DOI: 10.1007/s00408-014-9654-x.
[32]	YU P, WANG Z, LIU Y, et al.Marrow mesenchymal stem cells effectively reduce histologic changes in a rat model of chronic renal allograft rejection[J].Transplant Proc, 2017, 49(9):2194-2203.DOI: 10.1016/j.transproceed.2017.09.038.
[33]	YIP HK, LEE MS, SUN CK, et al.Therapeutic effects of adipose-derived mesenchymal stem cells against brain death-induced remote organ damage and post-heart transplant acute rejection[J].Oncotarget, 2017, 8(65):108692-108711.DOI: 10.18632/oncotarget.21433.
[34]	CHAMBERS DC, ENEVER D, LAWRENCE S, et al.Mesenchymal stromal cell therapy for chronic lung allograft dysfunction:results of a first-in-man study[J].Stem Cells Transl Med, 2017, 6(4):1152-1157.DOI: 10.1002/sctm.16-0372.
[35]	MA S, XIE N, LI W, et al.Immunobiology of mesenchymal stem cells[J].Cell Death Differ, 2014, 21(2):216-225.DOI: 10.1038/cdd.2013.158.
[36]	李睿, 董红丽, 刘汝斌, 等.骨髓间充质干细胞移植可促进移植胰岛周围新生血管形成[J].器官移植, 2017, 8(2):149-153.DOI: 10.3969/j.issn.1674-7445.2017.02.011. LI R, DONG HL, LIU RB, et al.Effect of bone mesenchymal stem cell transplantation on accelerating the vascularization surrounding transplant pancreatic islet[J].Organ Transplant, 2017, 8(2):149-153.DOI: 10.3969/j.issn.1674-7445.2017.02.011.
[37]	CORRADI-PERINI C, SANTOS TM, CAMARA NOS, et al.Co-transplantation of xenogeneic bone marrow-derived mesenchymal stem cells alleviates rejection of pancreatic islets in non-obese diabetic mice[J].Transplant Proc, 2017, 49(4):902-905.DOI: 10.1016/j.transproceed.2017.01.064.