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Allogeneic mesenchymal stem cells as induction therapy are safe and feasible in renal allografts: pilot results of a multicenter randomized controlled trial.
J Transl Med. 2018 03 07; 16(1):52.JT

Abstract

BACKGROUND

Kidneys from deceased donors are being used to meet the growing need for grafts. However, delayed graft function (DGF) and acute rejection incidences are high, leading to adverse effects on graft outcomes. Optimal induction intervention should include both renal structure injury repair and immune response suppression. Mesenchymal stem cells (MSCs) with potent anti-inflammatory, regenerative, and immune-modulatory properties are considered a candidate to prevent DGF and acute rejection in renal transplantation. Thus, this prospective multicenter paired study aimed to assess the clinical value of allogeneic MSCs as induction therapy to prevent both DGF and acute rejection in deceased donor renal transplantation.

METHODS

Forty-two renal allograft recipients were recruited and divided into trial and control groups. The trial group (21 cases) received 2 × 106/kg human umbilical-cord-derived MSCs (UC-MSCs) via the peripheral vein before renal transplantation, and 5 × 106 cells via the renal artery during the surgical procedure. All recipients received standard induction therapy. Incidences of DGF and biopsy-proven acute rejection were recorded postoperatively and severe postoperative complications were assessed. Graft and recipient survivals were also evaluated.

RESULTS

Treatment with UC-MSCs achieved comparable graft and recipient survivals with non-MSC treatment (P = 0.97 and 0.15, respectively). No increase in postoperative complications, including DGF and acute rejection, were observed (incidence of DGF: 9.5% in the MSC group versus 33.3% in the non-MSC group, P = 0.13; Incidence of acute rejection: 14.3% versus 4.8%, P = 0.61). Equal postoperative estimated glomerular filtration rates were found between the two groups (P = 0.88). All patients tolerated the MSCs infusion without adverse clinical effects. Additionally, a multiprobe fluorescence in situ hybridization assay revealed that UC-MSCs administered via the renal artery were absent from the recipient's biopsy sample.

CONCLUSIONS

Umbilical-cord-derived MSCs can be used as clinically feasible and safe induction therapy. Adequate timing and frequency of UC-MSCs administration may have a significant effect on graft and recipient outcomes. Trial registration NCT02490020 . Registered on June 29 2015.

Authors+Show Affiliations

Department of Renal Transplantation, The Third Affiliated Hospital, Sun Yat-sen University, Kaichuang Road 2693, Huangpu District, Guangzhou, 510530, People's Republic of China.Department of Renal Transplantation, The Third Affiliated Hospital, Sun Yat-sen University, Kaichuang Road 2693, Huangpu District, Guangzhou, 510530, People's Republic of China.Department of Renal Transplantation, The Third Affiliated Hospital, Sun Yat-sen University, Kaichuang Road 2693, Huangpu District, Guangzhou, 510530, People's Republic of China.Department of Renal Transplantation, Zhujiang Hospital, Southern Medical University, Gongye Road 253, Guangzhou, 510280, People's Republic of China.Department of Renal Transplantation, The Second Affiliated Hospital, Guangzhou Traditional Chinese Medicine University, Inner Ring Road 55, University City, Guangzhou, 510280, People's Republic of China.Department of Renal Transplantation, The Third Affiliated Hospital, Sun Yat-sen University, Kaichuang Road 2693, Huangpu District, Guangzhou, 510530, People's Republic of China.Department of Renal Transplantation, The Third Affiliated Hospital, Sun Yat-sen University, Kaichuang Road 2693, Huangpu District, Guangzhou, 510530, People's Republic of China.Department of Renal Transplantation, The Third Affiliated Hospital, Sun Yat-sen University, Kaichuang Road 2693, Huangpu District, Guangzhou, 510530, People's Republic of China.Department of Renal Transplantation, The Third Affiliated Hospital, Sun Yat-sen University, Kaichuang Road 2693, Huangpu District, Guangzhou, 510530, People's Republic of China.Department of Renal Transplantation, The Third Affiliated Hospital, Sun Yat-sen University, Kaichuang Road 2693, Huangpu District, Guangzhou, 510530, People's Republic of China.Department of Renal Transplantation, Zhujiang Hospital, Southern Medical University, Gongye Road 253, Guangzhou, 510280, People's Republic of China.Department of Renal Transplantation, The Second Affiliated Hospital, Guangzhou Traditional Chinese Medicine University, Inner Ring Road 55, University City, Guangzhou, 510280, People's Republic of China.Cell-gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital, Sun Yat-sen University, Tianhe Road 600, Guangzhou, 510630, People's Republic of China.Department of Renal Transplantation, The Third Affiliated Hospital, Sun Yat-sen University, Kaichuang Road 2693, Huangpu District, Guangzhou, 510530, People's Republic of China. sunqiq@mail.sysu.edu.cn.

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29514693

Citation

Sun, Qipeng, et al. "Allogeneic Mesenchymal Stem Cells as Induction Therapy Are Safe and Feasible in Renal Allografts: Pilot Results of a Multicenter Randomized Controlled Trial." Journal of Translational Medicine, vol. 16, no. 1, 2018, p. 52.
Sun Q, Huang Z, Han F, et al. Allogeneic mesenchymal stem cells as induction therapy are safe and feasible in renal allografts: pilot results of a multicenter randomized controlled trial. J Transl Med. 2018;16(1):52.
Sun, Q., Huang, Z., Han, F., Zhao, M., Cao, R., Zhao, D., Hong, L., Na, N., Li, H., Miao, B., Hu, J., Meng, F., Peng, Y., & Sun, Q. (2018). Allogeneic mesenchymal stem cells as induction therapy are safe and feasible in renal allografts: pilot results of a multicenter randomized controlled trial. Journal of Translational Medicine, 16(1), 52. https://doi.org/10.1186/s12967-018-1422-x
Sun Q, et al. Allogeneic Mesenchymal Stem Cells as Induction Therapy Are Safe and Feasible in Renal Allografts: Pilot Results of a Multicenter Randomized Controlled Trial. J Transl Med. 2018 03 7;16(1):52. PubMed PMID: 29514693.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Allogeneic mesenchymal stem cells as induction therapy are safe and feasible in renal allografts: pilot results of a multicenter randomized controlled trial. AU - Sun,Qipeng, AU - Huang,Zhengyu, AU - Han,Fei, AU - Zhao,Ming, AU - Cao,Ronghua, AU - Zhao,Daqiang, AU - Hong,Liangqing, AU - Na,Ning, AU - Li,Heng, AU - Miao,Bin, AU - Hu,Jianmin, AU - Meng,Fanhang, AU - Peng,Yanwen, AU - Sun,Qiquan, Y1 - 2018/03/07/ PY - 2017/11/27/received PY - 2018/02/20/accepted PY - 2018/3/9/entrez PY - 2018/3/9/pubmed PY - 2019/7/10/medline KW - Acute rejection KW - DGF KW - Delayed graft function KW - MSC KW - Mesenchymal stem cell KW - Renal transplantation SP - 52 EP - 52 JF - Journal of translational medicine JO - J Transl Med VL - 16 IS - 1 N2 - BACKGROUND: Kidneys from deceased donors are being used to meet the growing need for grafts. However, delayed graft function (DGF) and acute rejection incidences are high, leading to adverse effects on graft outcomes. Optimal induction intervention should include both renal structure injury repair and immune response suppression. Mesenchymal stem cells (MSCs) with potent anti-inflammatory, regenerative, and immune-modulatory properties are considered a candidate to prevent DGF and acute rejection in renal transplantation. Thus, this prospective multicenter paired study aimed to assess the clinical value of allogeneic MSCs as induction therapy to prevent both DGF and acute rejection in deceased donor renal transplantation. METHODS: Forty-two renal allograft recipients were recruited and divided into trial and control groups. The trial group (21 cases) received 2 × 106/kg human umbilical-cord-derived MSCs (UC-MSCs) via the peripheral vein before renal transplantation, and 5 × 106 cells via the renal artery during the surgical procedure. All recipients received standard induction therapy. Incidences of DGF and biopsy-proven acute rejection were recorded postoperatively and severe postoperative complications were assessed. Graft and recipient survivals were also evaluated. RESULTS: Treatment with UC-MSCs achieved comparable graft and recipient survivals with non-MSC treatment (P = 0.97 and 0.15, respectively). No increase in postoperative complications, including DGF and acute rejection, were observed (incidence of DGF: 9.5% in the MSC group versus 33.3% in the non-MSC group, P = 0.13; Incidence of acute rejection: 14.3% versus 4.8%, P = 0.61). Equal postoperative estimated glomerular filtration rates were found between the two groups (P = 0.88). All patients tolerated the MSCs infusion without adverse clinical effects. Additionally, a multiprobe fluorescence in situ hybridization assay revealed that UC-MSCs administered via the renal artery were absent from the recipient's biopsy sample. CONCLUSIONS: Umbilical-cord-derived MSCs can be used as clinically feasible and safe induction therapy. Adequate timing and frequency of UC-MSCs administration may have a significant effect on graft and recipient outcomes. Trial registration NCT02490020 . Registered on June 29 2015. SN - 1479-5876 UR - https://www.unboundmedicine.com/medline/citation/29514693/Allogeneic_mesenchymal_stem_cells_as_induction_therapy_are_safe_and_feasible_in_renal_allografts:_pilot_results_of_a_multicenter_randomized_controlled_trial_ L2 - https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1422-x DB - PRIME DP - Unbound Medicine ER -