TY - JOUR
T1 - Autologous bone marrow-derived mesenchymal stromal cell therapy with early tacrolimus withdrawal: The randomized prospective, single-center, open-label TRITON study
AU - Reinders, Marlies E. J.
AU - Groeneweg, Koen E.
AU - Hendriks, Sanne H.
AU - Bank, Jonna R.
AU - Dreyer, Geertje J.
AU - de Vries, Aiko P. J.
AU - van Pel, Melissa
AU - Roelofs, Helene
AU - Huurman, Volkert A. L.
AU - Meij, Paula
AU - Moes, Dirk J. A. R.
AU - Fibbe, Willem E.
AU - Claas, Frans H. J.
AU - Roelen, Dave L.
AU - van Kooten, Cees
AU - Kers, Jesper
AU - Heidt, Sebastiaan
AU - Rabelink, Ton J.
AU - de Fijter, Johan W.
N1 - Funding Information: We thank the research department of internal medicine of the Leiden University Medical Center for their help with the study visits. We thank the research technicians from the Transplant Immunology lab for technical assistance with the immune monitoring. This investigator-initiated study was partially funded by unrestricted research grants from Astellas and Novartis. The funders had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. Part of this work was supported by a grant from ZonMW-TAS program nr 116004104. Publisher Copyright: © 2021 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.
PY - 2021/9
Y1 - 2021/9
N2 - After renal transplantation, there is a need for immunosuppressive regimens which effectively prevent allograft rejection, while preserving renal function and minimizing side effects. From this perspective, mesenchymal stromal cell (MSC) therapy is of interest. In this randomized prospective, single-center, open-label trial, we compared MSCs infused 6 and 7 weeks after renal transplantation and early tacrolimus withdrawal with a control tacrolimus group. Primary end point was quantitative evaluation of interstitial fibrosis in protocol biopsies at 4 and 24 weeks posttransplant. Secondary end points included acute rejection, graft loss, death, renal function, adverse events, and immunological responses. Seventy patients were randomly assigned of which 57 patients were included in the final analysis (29 MSC; 28 controls). Quantitative progression of fibrosis failed to show benefit in the MSC group and GFR remained stable in both groups. One acute rejection was documented (MSC group), while subclinical rejection in week 24 protocol biopsies occurred in seven patients (four MSC; three controls). In the MSC group, regulatory T cell numbers were significantly higher compared to controls (p =.014, week 24). In conclusion, early tacrolimus withdrawal with MSC therapy was safe and feasible without increased rejection and with preserved renal function. MSC therapy is a potentially useful approach after renal transplantation.
AB - After renal transplantation, there is a need for immunosuppressive regimens which effectively prevent allograft rejection, while preserving renal function and minimizing side effects. From this perspective, mesenchymal stromal cell (MSC) therapy is of interest. In this randomized prospective, single-center, open-label trial, we compared MSCs infused 6 and 7 weeks after renal transplantation and early tacrolimus withdrawal with a control tacrolimus group. Primary end point was quantitative evaluation of interstitial fibrosis in protocol biopsies at 4 and 24 weeks posttransplant. Secondary end points included acute rejection, graft loss, death, renal function, adverse events, and immunological responses. Seventy patients were randomly assigned of which 57 patients were included in the final analysis (29 MSC; 28 controls). Quantitative progression of fibrosis failed to show benefit in the MSC group and GFR remained stable in both groups. One acute rejection was documented (MSC group), while subclinical rejection in week 24 protocol biopsies occurred in seven patients (four MSC; three controls). In the MSC group, regulatory T cell numbers were significantly higher compared to controls (p =.014, week 24). In conclusion, early tacrolimus withdrawal with MSC therapy was safe and feasible without increased rejection and with preserved renal function. MSC therapy is a potentially useful approach after renal transplantation.
KW - clinical research/practice
KW - clinical trial
KW - immune regulation
KW - immunosuppression/immune modulation
KW - immunosuppressive regimens – minimization/withdrawal
KW - kidney transplantation/nephrology
KW - kidney transplantation: living donor
KW - stem cells
UR - http://www.scopus.com/inward/record.url?scp=85102623593&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/ajt.16528
DO - https://doi.org/10.1111/ajt.16528
M3 - Article
C2 - 33565206
SN - 1600-6135
VL - 21
SP - 3055
EP - 3065
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 9
ER -