دورية أكاديمية
Efficacy and Safety of Bone Marrow-Derived Mesenchymal Stem Cells for Chronic Antibody-Mediated Rejection After Kidney Transplantation- A Single-Arm, Two-Dosing-Regimen, Phase I/II Study.
| العنوان: | Efficacy and Safety of Bone Marrow-Derived Mesenchymal Stem Cells for Chronic Antibody-Mediated Rejection After Kidney Transplantation- A Single-Arm, Two-Dosing-Regimen, Phase I/II Study. |
|---|---|
| المؤلفون: | Wei Y; Organ Transplant Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Chen X; Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China., Zhang H; Organ Transplant Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Su Q; Organ Transplant Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Peng Y; The Biotherapy Center, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Fu Q; Organ Transplant Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Li J; Organ Transplant Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Gao Y; Organ Transplant Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Li X; Organ Transplant Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Yang S; Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Ye Q; Organ Transplant Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Huang H; Organ Transplant Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Deng R; Organ Transplant Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Li G; Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China., Xu B; Organ Transplant Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Wu C; Organ Transplant Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Wang J; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Zhang X; Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China., Su X; Organ Transplant Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Liu L; Organ Transplant Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Xiang AP; Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China., Wang C; Organ Transplant Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. |
| المصدر: | Frontiers in immunology [Front Immunol] 2021 Jun 25; Vol. 12, pp. 662441. Date of Electronic Publication: 2021 Jun 25 (Print Publication: 2021). |
| نوع المنشور: | Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
| مواضيع طبية MeSH: | Cell- and Tissue-Based Therapy/*methods , Graft Rejection/*immunology , Graft Rejection/*prevention & control , Kidney Transplantation/*adverse effects , Mesenchymal Stem Cell Transplantation/*methods , Transplantation, Homologous/*adverse effects, Adolescent ; Adult ; Aged ; Antibodies ; Bone Marrow Cells/immunology ; Female ; Humans ; Immunomodulation ; Immunosuppressive Agents/therapeutic use ; Kidney/pathology ; Male ; Middle Aged ; Retrospective Studies ; Young Adult |
| مستخلص: | Objective: To investigate the efficacy and safety of bone marrow-derived mesenchymal stem cells (BM-MSCs) on chronic active antibody-mediated rejection (cABMR) in the kidney allograft. Methods: Kidney recipients with biopsy-proven cABMR were treated with allogeneic third-party BM-MSCs in this open-label, single-arm, single-center, two-dosing-regimen phase I/II clinical trial. In Regimen 1 (n=8), BM-MSCs were administered intravenously at a dose of 1.0×10 6 cells/kg monthly for four consecutive months, while in Regimen 2 (n=15), the BM-MSCs dose was 1.0×10 6 cells/kg weekly during four consecutive weeks. The primary endpoints were the absolute change of estimated glomerular filtration rate (eGFR) from baseline (delta eGFR) and the incidence of adverse events associated with BM-MSCs administration 24 months after the treatment. Contemporaneous cABMR patients who did not receive BM-MSCs were retrospectively analyzed as the control group (n =30). Results: Twenty-three recipients with cABMR received BM-MSCs. The median delta eGFR of the total BM-MSCs treated patients was -4.3 ml/min per 1.73m 2 (interquartile range, IQR -11.2 to 1.2) 2 years after BM-MSCs treatment (P=0.0233). The median delta maximum donor-specific antibody (maxDSA) was -4310 (IQR -9187 to 1129) at 2 years (P=0.0040). The median delta eGFR of the control group was -12.7 ml/min per 1.73 m 2 (IQR -22.2 to -3.5) 2 years after the diagnosis, which was greater than that of the BM-MSCs treated group (P=0.0342). The incidence of hepatic enzyme elevation, BK polyomaviruses (BKV) infection, cytomegalovirus (CMV) infection was 17.4%, 17.4%, 8.7%, respectively. There was no fever, anaphylaxis, phlebitis or venous thrombosis, cardiovascular complications, or malignancy after BM-MSCs administration. Flow cytometry analysis showed a significant decreasing trend of CD27 - IgD - double negative B cells subsets and trend towards the increase of CD3 + CD4 + PD-1 + /lymphocyte population after MSCs therapy. Multiplex analysis found TNF-α, CXCL10, CCL4, CCL11 and RANTES decreased after MSCs treatment. Conclusion: Kidney allograft recipients with cABMR are tolerable to BM-MSCs. Immunosuppressive drugs combined with intravenous BM-MSCs can delay the deterioration of allograft function, probably by decreasing DSA level and reducing DSA-induced injury. The underlying mechanism may involve immunomodulatory effect of MSCs on peripheral B and T cells subsets. Competing Interests: The authors declare this study was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Wei, Chen, Zhang, Su, Peng, Fu, Li, Gao, Li, Yang, Ye, Huang, Deng, Li, Xu, Wu, Wang, Zhang, Su, Liu, Xiang and Wang.) |
| References: | J Exp Med. 1998 Nov 2;188(9):1679-89. (PMID: 9802980) Theranostics. 2019 Jun 24;9(16):4633-4647. (PMID: 31367246) Lancet. 2004 May 1;363(9419):1439-41. (PMID: 15121408) Stem Cells Int. 2021 Feb 10;2021:6672644. (PMID: 33628269) Stem Cells Transl Med. 2013 Feb;2(2):107-11. (PMID: 23349326) Transplantation. 2011 May 15;91(9):1010-8. (PMID: 21403590) Front Immunol. 2019 Oct 18;10:2458. (PMID: 31681331) Cell Stem Cell. 2018 Jun 01;22(6):824-833. (PMID: 29859173) Cell Stem Cell. 2008 Feb 7;2(2):141-50. (PMID: 18371435) Clin J Am Soc Nephrol. 2011 Feb;6(2):412-22. (PMID: 20930086) Am J Transplant. 2018 Feb;18(2):293-307. (PMID: 29243394) Front Cell Dev Biol. 2020 Jan 29;8:10. (PMID: 32064259) Leukemia. 2015 Mar;29(3):636-46. (PMID: 25034146) Kidney Int. 2019 Mar;95(3):693-707. (PMID: 30528263) J Transl Med. 2018 Feb 15;16(1):30. (PMID: 29448960) Lupus. 2018 Nov;27(13):2161-2165. (PMID: 30290717) Transplant Res. 2013 Oct 25;2(1):17. (PMID: 24160259) Nat Commun. 2020 Jul 6;11(1):3434. (PMID: 32632085) J Transl Med. 2015 Nov 04;13:344. (PMID: 26537851) Front Immunol. 2018 Dec 21;9:3053. (PMID: 30622539) Front Immunol. 2019 Jun 06;10:1288. (PMID: 31244839) Immunol Cell Biol. 2013 Jan;91(1):40-51. (PMID: 23207278) Transpl Immunol. 2014 Aug;31(2):65-74. (PMID: 24978830) J Transl Med. 2018 Mar 7;16(1):52. (PMID: 29514693) Transplantation. 2021 Mar 1;105(3):648-659. (PMID: 33617203) Stem Cells Dev. 2015 Jan 1;24(1):93-103. (PMID: 25036865) Front Immunol. 2019 Jun 04;10:1287. (PMID: 31231393) Arthritis Res Ther. 2015 Mar 14;17:61. (PMID: 25888920) Curr Opin Organ Transplant. 2014 Feb;19(1):65-72. (PMID: 24370985) Clin Immunol. 2008 Feb;126(2):189-201. (PMID: 18077220) Nat Commun. 2018 May 1;9(1):1758. (PMID: 29717110) N Engl J Med. 2018 Sep 20;379(12):1150-1160. (PMID: 30231232) J Immunol. 2009 May 15;182(10):5994-6002. (PMID: 19414750) Nat Rev Nephrol. 2016 Apr;12(4):241-53. (PMID: 26853275) N Engl J Med. 2013 Sep 26;369(13):1215-26. (PMID: 24066742) Nat Rev Nephrol. 2018 Aug;14(8):493-507. (PMID: 29895977) Front Med (Lausanne). 2020 Apr 07;7:85. (PMID: 32318574) JAMA. 2012 Mar 21;307(11):1169-77. (PMID: 22436957) Immunity. 2018 Oct 16;49(4):725-739.e6. (PMID: 30314758) Transplantation. 2013 Jan 15;95(1):161-8. (PMID: 23263506) Am J Transplant. 2015 Jan;15 Suppl 2:1-34. (PMID: 25626344) Am J Transplant. 2020 Sep;20(9):2318-2331. (PMID: 32463180) Arthritis Res Ther. 2014 Mar 25;16(2):R79. (PMID: 24661633) Science. 2016 Dec 2;354(6316):1165-1169. (PMID: 27789799) Pediatr Nephrol. 2016 Jun;31(6):1001-10. (PMID: 26692023) Stem Cells Dev. 2012 Nov 20;21(17):3125-35. (PMID: 22494435) Stem Cells Transl Med. 2020 Apr;9(4):427-432. (PMID: 31872574) J Immunol. 2007 May 15;178(10):6624-33. (PMID: 17475894) Nat Rev Immunol. 2018 Mar;18(3):153-167. (PMID: 28990585) Transplantation. 2020 May;104(5):911-922. (PMID: 31895348) Front Immunol. 2020 Dec 03;11:611004. (PMID: 33343585) |
| فهرسة مساهمة: | Keywords: alloimmunity; antibody-mediated allograft rejection; kidney transplantation; mesenchymal stem cells; stem cell therapy |
| المشرفين على المادة: | 0 (Antibodies) 0 (Immunosuppressive Agents) |
| تواريخ الأحداث: | Date Created: 20210712 Date Completed: 20211014 Latest Revision: 20211014 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC8267917 |
| DOI: | 10.3389/fimmu.2021.662441 |
| PMID: | 34248942 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1664-3224 |
|---|---|
| DOI: | 10.3389/fimmu.2021.662441 |