细胞治疗在肾脏移植中的应用前景*

doi:10.3969/j.issn.1671-2587.2022.06.002

临床输血与检验 ›› 2022, Vol. 24 ›› Issue (6): 687-692.DOI: 10.3969/j.issn.1671-2587.2022.06.002

细胞治疗在肾脏移植中的应用前景^*

李杨, 戎瑞明

200032 上海,复旦大学附属中山医院输血科（李杨,戎瑞明）; 复旦大学附属中山医院上海市器官移植重点实验室（戎瑞明）

收稿日期:2022-09-15 发布日期:2023-01-05
通讯作者: 戎瑞明,男,教授,博士,主要从事输血医学和器官移植研究工作,（E-mail）rong.ruiming@zs-hospital.sh.cn。
作者简介:李杨（1992-）,女,技师,硕士,主要从事输血医学研究工作,（E-mail）li.yang2@zs-hospital.sh.cn。
基金资助:
*本课题受国家重点研发计划项目（No.2018YFA0107501）和国家自然科学基金面上项目（No.81970646）资助

Application Prospect of Cell Therapy in Kidney Transplantation

LI Yang, RONG Rui-ming

Blood Transfusion Department of Zhongshan Hospital Affiliated to Fudan University, Shanghai 200032

Received:2022-09-15 Published:2023-01-05

摘要/Abstract

摘要： 当患者出现终末期器官衰竭时,可进行器官移植,延续患者生命。然而移植术后带来的器官结构功能损伤和免疫排斥反应,影响患者生存时长和质量。细胞治疗已被广泛接受为再生医学中有效的治疗方式,主要分为干细胞治疗和免疫细胞治疗。细胞治疗在器官移植中已取得显著的治疗效果。本文以肾脏移植为例,讨论如何利用细胞治疗调节器官移植免疫平衡,延长移植器官和患者的生命力,为器官移植耐受诱导和维持提供新的见解。

关键词: 细胞治疗, 肾脏移植, 免疫细胞

Abstract: Organ transplantation can be carried out to prolong their lives when patients get end-stage organ failure. However, organ structure and function damage and immune rejection after transplantation impair patients' survival time and quality. Cell therapy has been widely accepted as an effective way in regenerative medicine and it is mainly divided into stem cell therapy and immune cell therapy. Cell therapy has achieved significant therapeutic effect in organ transplantation. Taking kidney transplantation as an example, this paper will discuss how to regulate the immune balance of organ transplantation and prolong the vitality of transplanted organs and patients by cell therapy. These will provide new insights for the induction and maintenance of organ transplantation tolerance.

Key words: Cell therapy, Kidney transplantation, Immune cells

中图分类号:

R392.4

李杨, 戎瑞明. 细胞治疗在肾脏移植中的应用前景^*[J]. 临床输血与检验, 2022, 24(6): 687-692.

LI Yang, RONG Rui-ming. Application Prospect of Cell Therapy in Kidney Transplantation[J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2022, 24(6): 687-692.

参考文献

[1] PHILLIPS S,HEUBERGER R.Metabolic disorders following kidney transplantation[J].J Ren Nutr, 2012, 22(5): 451-460.e451.
[2] 赵海涛,刘致中.肾移植前免疫诱导治疗的进展[J].临床泌尿外科杂志,2013,28(03):233-238.
[3] ALLISON T L.Immunosuppressive therapy in transplantation[J].Nurs Clin North Am,2016,51(1):107-120.
[4] NI X H,WANG Q,GU J,et al.Clinical and basic research progress on treg-induced immune tolerance in liver transplantation[J]. Front Immunol,2021,12:535012.
[5] YANG F,LI Y,WU T T,et al.NFα-induced M-MDSCs promote transplant immune tolerance via nitric oxide[J]. J Mol Med (Berl),2016,94(8):911-920.
[6] ISSA F,STROBER S,LEVENTHAL J R,et al.The fourth international workshop on clinical transplant tolerance[J]. Am J Transplant,2021,21(1):21-31.
[7] PODESTÀ M A,REMUZZI G,CASIRAGHI F.Mesenchymal stromal cell therapy in solid organ transplantation[J]. Front Immunol,2021,11:618243.
[8] LAUKOVÁ L,WEISS R,SEMAK V,et al.Desialylation of platelet surface glycans enhances platelet adhesion to adsorbent polymers for lipoprotein apheresis[J]. Int J Artif Organs,2021,44(6):378-384.
[9] DONG C L,ZHAO C,WANG F.Clinical benefit of high tibial osteotomy combined with the intervention of platelet-rich plasma for severe knee osteoarthritis[J]. J Orthop Surg Res,2022,17(1):405.
[10] OBEROI S,ROBINSON P D,CATAUDELLA D,et al.Physical activity reduces fatigue in patients with cancer and hematopoietic stem cell transplant recipients:a systematic review and meta-analysis of randomized trials[J]. Crit Rev Oncol Hematol,2018,122:52-59.
[11] STAUDT R E,CARLSON R D,SNOOK A E.Targeting gastrointestinal cancers with chimeric antigen receptor (CAR)-T cell therapy[J]. Cancer Biol Ther,2022,23(1):127-133.
[12] MORATH C,SCHMITT A,ZEIER M,et al.Cell therapy for immunosuppression after kidney transplantation[J]. Langenbecks Arch Surg,2015,400(5):541-550.
[13] GOSWAMI T K,SINGH M,DHAWAN M,et al.Regulatory T cells (Tregs) and their therapeutic potential against autoimmune disorders-Advances and challenges[J].Hum Vaccin Immunother,2022,18(1):2035117.
[14] PEFANIS A,IERINO F L,MURPHY J M,et al.Regulated necrosis in kidney ischemia-reperfusion injury[J]. Kidney Int,2019,96(2):291-301.
[15] PERAZELLA M A.Drug-induced acute kidney injury:diverse mechanisms of tubular injury[J]. Curr Opin Crit Care,2019,25(6):550-557.
[16] CHANG Y M,CHOU Y T,KAN W C,et al.Sepsis and acute kidney injury:a review focusing on the bidirectional interplay[J]. Int J Mol Sci,2022,23(16):9159.
[17] CHÁVEZ-IÑIGUEZ J S,NAVARRO-GALLARDO G J,MEDINA-GONZÁLEZ R,et al.Acute kidney injury caused by obstructive nephropathy[J]. Int J Nephrol,2020,2020:8846622.
[18] 邱月,戚贵生,杨橙,等. 不同时间输注骨髓间充质干细胞对大鼠肾脏缺血再灌注损伤的影响[J]. 中华器官移植杂志,2012,33(4):246-249.
[19] CAO J Y,WANG B,TANG T T,et al.Exosomal miR-125b-5p deriving from mesenchymal stem cells promotes tubular repair by suppression of p53 in ischemic acute kidney injury[J]. Theranostics,2021,11(11):5248-5266.
[20] BUZHOR E,OMER D,HARARI-STEINBERG O,et al.Reactivation of NCAM1 defines a subpopulation of human adult kidney epithelial cells with clonogenic and stem/progenitor properties[J]. Am J Pathol,2013,183(5):1621-1633.
[21] TAKASATO M,ER P X,BECROFT M,et al.Directing human embryonic stem cell differentiation towards a renal lineage generates a self-organizing kidney[J]. Nat Cell Biol,2014,16(1):118-126.
[22] LAM A Q,FREEDMAN B S,MORIZANE R,et al.Rapid and efficient differentiation of human pluripotent stem cells into intermediate mesoderm that forms tubules expressing kidney proximal tubular markers[J]. J Am Soc Nephrol,2014,25(6):1211-1225.
[23] YAN J J,RYU J H,PIAO H L,et al.Granulocyte colony-stimulating factor attenuates renal ischemia-reperfusion injury by inducing myeloid-derived suppressor cells[J]. J Am Soc Nephrol,2020,31(4):731-746.
[24] GANDOLFO M T,JANG H R,BAGNASCO S M,et al.Foxp3+ regulatory T cells participate in repair of ischemic acute kidney injury[J]. Kidney Int,2009,76(7):717-729.
[25] CHEUK Y C,XU S H,ZHU D,et al.Monocytic myeloid-derived suppressor cells inhibit myofibroblastic differentiation in mesenchymal stem cells through IL-15 secretion[J]. Front Cell Dev Biol,2022,10:817402.
[26] LO SICCO C,REVERBERI D,BALBI C,et al.Mesenchymal stem cell-derived extracellular vesicles as mediators of anti-inflammatory effects:endorsement of macrophage polarization[J]. Stem Cells Transl Med,2017,6(3):1018-1028.
[27] TAN J M,WU W Z,XU X M,et al.Induction therapy with autologous mesenchymal stem cells in living-related kidney transplants:a randomized controlled trial[J]. JAMA,2012,307(11):1169-1177.
[28] CLARK F J,GREGG R,PIPER K,et al.Chronic graft-versus-host disease is associated with increased numbers of peripheral blood CD4+CD25high regulatory T cells[J]. Blood,2004,103(6):2410-2416.
[29] SAKAGUCHI S,MIYARA M,COSTANTINO C M,et al.FOXP3+ regulatory T cells in the human immune system[J]. Nat Rev Immunol,2010,10(7):490-500.
[30] CRELLIN N K,GARCIA R V,HADISFAR O,et al.Human CD4+ T cells express TLR5 and its ligand flagellin enhances the suppressive capacity and expression of FOXP3 in CD4+CD25+ T regulatory cells[J]. J Immunol,2005,175(12):8051-8059.
[31] ROEMHILD A,OTTO N M,MOLL G,et al.Regulatory T cells for minimising immune suppression in kidney transplantation:phase I/IIa clinical trial[J]. BMJ,2020:m3734.
[32] LIAO T, XUE Y, ZHAO D, et al.In Vivo Attenuation of Antibody-Mediated Acute Renal Allograft Rejection by Ex Vivo TGF-beta-Induced CD4(+)Foxp3(+) Regulatory T Cells[J]. Front Immunol, 2017, 8: 1334.
[33] BOARDMAN D A,PHILIPPEOS C,FRUHWIRTH G O,et al.Expression of a chimeric antigen receptor specific for donor HLA class I enhances the potency of human regulatory T cells in preventing human skin transplant rejection[J]. Am J Transplant,2017,17(4):931-943.
[34] NOYAN F,ZIMMERMANN K,HARDTKE-WOLENSKI M,et al.Prevention of allograft rejection by use of regulatory T cells with an MHC-specific chimeric antigen receptor[J]. Am J Transplant,2017,17(4):917-930.
[35] GABRILOVICH D I,NAGARAJ S.Myeloid-derived suppressor cells as regulators of the immune system[J]. Nat Rev Immunol,2009,9(3):162-174.
[36] PAN P Y,MA G,WEBER K J,et al.Immune stimulatory receptor CD40 is required for T-cell suppression and T regulatory cell activation mediated by myeloid-derived suppressor cells in cancer[J]. Cancer Res,2010,70(1):99-108.
[37] DE WILDE V,VAN ROMPAEY N,HILL M,et al.Endotoxin-induced myeloid-derived suppressor cells inhibit alloimmune responses via heme oxygenase-1[J]. Am J Transplant,2009,9(9):2034-2047.
[38] KOEHN B H,APOSTOLOVA P,HAVERKAMP J M,et al.GVHD-associated,inflammasome-mediated loss of function in adoptively transferred myeloid-derived suppressor cells[J]. Blood,2015,126(13):1621-1628.
[39] DUGAST A S,HAUDEBOURG T,COULON F,et al.Myeloid-derived suppressor cells accumulate in kidney allograft tolerance and specifically suppress effector T cell expansion[J]. J Immunol,2008,180(12):7898-7906.
[40] LUAN Y,MOSHEIR E,MENON M C,et al.Monocytic myeloid-derived suppressor cells accumulate in renal transplant patients and mediate CD4(+) Foxp3(+) Treg expansion[J]. Am J Transplant,2013,13(12):3123-3131.
[41] BOTTOMLEY M J,HARDEN P N,WOOD K J,et al.Dampened inflammatory signalling and myeloid-derived suppressor-like cell accumulation reduces circulating monocytic HLA-DR density and may associate with malignancy risk in long-term renal transplant recipients[J]. Front Immunol,2022,13:901273.
[42] HOCK B D,MACKENZIE K A,CROSS N B,et al.Renal transplant recipients have elevated frequencies of circulating myeloid-derived suppressor cells[J]. Nephrol Dial Transplant,2012,27(1):402-410.
[43] STARZL T E,DEMETRIS A J,MURASE N,et al.Cell migration,chimerism,and graft acceptance[J]. Lancet,1992,339(8809):1579-1582.
[44] REISNER Y,GUR H,REICH-ZELIGER S,et al.Hematopoietic stem cell transplantation across major genetic barriers:tolerance induction by megadose CD34 cells and other veto cells[J]. Ann N Y Acad Sci,2005,1044:70-83.
[45] LEVENTHAL J,ABECASSIS M,MILLER J,et al. Chimerism and tolerance without GVHD or engraftment syndrome in HLA-mismatched combined kidney and hematopoietic stem cell transplantation[J]. Sci Transl Med,2012,4(124):124ra28.
[46] ZHAO Y,ZHU X Y,SONG T R,et al.Mesenchymal stem cells protect renal tubular cells via TSG-6 regulating macrophage function and phenotype switching[J]. Am J Physiol Renal Physiol,2021,320(3):F454-F463.
[47] LUIZ R,RAMPASO R R,DOS SANTOS A A C,et al. BM-MSC-derived small extracellular vesicles (sEV) from trained animals presented nephroprotective potential in unilateralureteral obstruction model[J]. J Venom Anim Toxins Incl Trop Dis,2021,27:e20200187.
[48] YANG C C,SUNG P H,CHEN K H,et al.Valsartan-and melatonin-supported adipose-derived mesenchymal stem cells preserve renal function in chronic kidney disease rat through upregulation of prion protein participated in promoting PI3K-Akt-mTOR signaling and cell proliferation[J]. Biomed Pharmacother,2022,146:112551.
[49] Siddiqi S,Klomjit N,Jiang K,et al. Efficacy of human embryonic stem cells compared to adipose tissue-derived human mesenchymal stem/stromal cells for repair of murine post-stenotic kidneys[J]. Stem Cell Rev Rep,2022:2022 Sep 1.
[50] IMAFUKU A,OKA M,MIYABE Y,et al.Rat mesenchymal stromal cell sheets suppress renal fibrosis via microvascular protection[J]. Stem Cells Transl Med,2019,8(12):1330-1341.
[51] HUUSKES B M,WISE A F,COX A J,et al.Combination therapy of mesenchymal stem cells and serelaxin effectively attenuates renal fibrosis in obstructive nephropathy[J]. FASEB J,2015,29(2):540-553.
[52] QIU Y,CAO Y R,TU G W,et al.Myeloid-derived suppressor cells alleviate renal fibrosis progression via regulation of CCL5-CCR5 axis[J]. Front Immunol,2021,12:698894.

细胞治疗在肾脏移植中的应用前景^*

Application Prospect of Cell Therapy in Kidney Transplantation

RichHTML

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 2

编辑推荐

Metrics

本文评价

关于本刊

作者中心

在线期刊

访问统计

联系我们

[1]	詹林盛. 输血及细胞治疗的可视化评价技术研究^*[J]. 临床输血与检验, 2017, 19(6): 537-539.
[2]	刘强, 肖莉, 李国良. 江西地区终末期肾功能衰竭患者HLA基因多态性分析[J]. 临床输血与检验, 2016, 18(5): 430-434.