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Infusion of third-party mesenchymal stromal cells after kidney transplantation: a phase I-II, open-label, clinical study.
Kidney Int. 2019 03; 95(3):693-707.KI

Abstract

Mesenchymal stromal cells (MSCs) exhibit anti-inflammatory and immune-regulatory properties, and preclinical studies suggest a potential benefit in solid organ transplantation. We report on the 1-year follow-up of an open-label phase I-II trial of a single infusion of third-party MSC post-kidney transplantation, in addition to standard immunosuppression. Ten kidney transplant recipients from deceased donors received third-party bone marrow MSCs (∼2 × 106/kg) on day 3 ± 2 post-transplant and were compared to 10 concurrent controls. No adverse effects were noted at MSC injection. One participant with a history of cardiac disease had a non-ST-elevation myocardial infarction approximately 3 hours after MSC infusion. Incidences of opportunistic infections and acute rejection were similar. At day 7 post-transplant, estimated glomerular filtration rate (eGFR) in MSC-treated recipients reached 48.6 ml/min/1.73m2, compared to 32.5 ml/min/1.73m2 in controls and 29.3 ml/min/1.73m2 in our overall cohort of kidney transplant recipients. No difference in eGFR was found at 1 year. MSC-treated recipients showed increased frequencies of regulatory T cells at day 30, with no significant change in B cell frequencies compared to concurrent controls. Four MSC-treated participants developed antibodies against MSC or shared kidney-MSC HLA, with only 1 with MFI >1500. A single infusion of third-party MSC following kidney transplantation appears to be safe, with one cardiac event of unclear relationship to the intervention. MSC therapy is associated with increased regulatory T cell proportion and with improved early allograft function. Long-term effects, including potential immunization against MSC, remain to be studied.

Authors+Show Affiliations

Division of Nephrology, CHU of Liège, University of Liège (CHU ULiège), Liège, Belgium; Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA), Cardiovascular Sciences, University of Liège (ULiège), Liège, Belgium.Division of Nephrology, CHU of Liège, University of Liège (CHU ULiège), Liège, Belgium.Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA), Cardiovascular Sciences, University of Liège (ULiège), Liège, Belgium; Division of Abdominal Surgery and Transplantation, CHU of Liège, University of Liège (CHU ULiège), Liège, Belgium.Division of Nephrology, CHU of Liège, University of Liège (CHU ULiège), Liège, Belgium.Division of Abdominal Surgery and Transplantation, CHU of Liège, University of Liège (CHU ULiège), Liège, Belgium.Laboratory of Cell and Gene Therapy (LTCG), CHU of Liège, University of Liège (CHU ULiège), Liège, Belgium; GIGA, I3-Hematology, University of Liège (ULiège), Liège, Belgium; Division of Hematology, CHU of Liège, University of Liège (CHU ULiège), Liège, Belgium.Laboratory of Cell and Gene Therapy (LTCG), CHU of Liège, University of Liège (CHU ULiège), Liège, Belgium.Laboratory of Cell and Gene Therapy (LTCG), CHU of Liège, University of Liège (CHU ULiège), Liège, Belgium.Laboratory of Cell and Gene Therapy (LTCG), CHU of Liège, University of Liège (CHU ULiège), Liège, Belgium.Division of Immunohematology, CHU of Liège, University of Liège (CHU ULiège), Liège, Belgium.Division of Pathology, CHU of Liège, University of Liège (CHU ULiège), Liège, Belgium.KU Leuven Kulak, Department of Public Health and Primary Care, University of Leuven, Kortrijk, Belgium.Laboratory of Cell and Gene Therapy (LTCG), CHU of Liège, University of Liège (CHU ULiège), Liège, Belgium; GIGA, I3-Hematology, University of Liège (ULiège), Liège, Belgium; Division of Hematology, CHU of Liège, University of Liège (CHU ULiège), Liège, Belgium.Division of Nephrology, CHU of Liège, University of Liège (CHU ULiège), Liège, Belgium; Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA), Cardiovascular Sciences, University of Liège (ULiège), Liège, Belgium. Electronic address: francois.jouret@chuliege.be.Laboratory of Cell and Gene Therapy (LTCG), CHU of Liège, University of Liège (CHU ULiège), Liège, Belgium; GIGA, I3-Hematology, University of Liège (ULiège), Liège, Belgium; Division of Hematology, CHU of Liège, University of Liège (CHU ULiège), Liège, Belgium.

Pub Type(s)

Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30528263

Citation

Erpicum, Pauline, et al. "Infusion of Third-party Mesenchymal Stromal Cells After Kidney Transplantation: a Phase I-II, Open-label, Clinical Study." Kidney International, vol. 95, no. 3, 2019, pp. 693-707.
Erpicum P, Weekers L, Detry O, et al. Infusion of third-party mesenchymal stromal cells after kidney transplantation: a phase I-II, open-label, clinical study. Kidney Int. 2019;95(3):693-707.
Erpicum, P., Weekers, L., Detry, O., Bonvoisin, C., Delbouille, M. H., Grégoire, C., Baudoux, E., Briquet, A., Lechanteur, C., Maggipinto, G., Somja, J., Pottel, H., Baron, F., Jouret, F., & Beguin, Y. (2019). Infusion of third-party mesenchymal stromal cells after kidney transplantation: a phase I-II, open-label, clinical study. Kidney International, 95(3), 693-707. https://doi.org/10.1016/j.kint.2018.08.046
Erpicum P, et al. Infusion of Third-party Mesenchymal Stromal Cells After Kidney Transplantation: a Phase I-II, Open-label, Clinical Study. Kidney Int. 2019;95(3):693-707. PubMed PMID: 30528263.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Infusion of third-party mesenchymal stromal cells after kidney transplantation: a phase I-II, open-label, clinical study. AU - Erpicum,Pauline, AU - Weekers,Laurent, AU - Detry,Olivier, AU - Bonvoisin,Catherine, AU - Delbouille,Marie-Hélène, AU - Grégoire,Céline, AU - Baudoux,Etienne, AU - Briquet,Alexandra, AU - Lechanteur,Chantal, AU - Maggipinto,Gianni, AU - Somja,Joan, AU - Pottel,Hans, AU - Baron,Frédéric, AU - Jouret,François, AU - Beguin,Yves, Y1 - 2018/12/06/ PY - 2018/03/07/received PY - 2018/07/25/revised PY - 2018/08/23/accepted PY - 2018/12/12/pubmed PY - 2020/2/15/medline PY - 2018/12/12/entrez KW - cell therapy KW - kidney transplantation KW - mesenchymal stromal cells SP - 693 EP - 707 JF - Kidney international JO - Kidney Int. VL - 95 IS - 3 N2 - Mesenchymal stromal cells (MSCs) exhibit anti-inflammatory and immune-regulatory properties, and preclinical studies suggest a potential benefit in solid organ transplantation. We report on the 1-year follow-up of an open-label phase I-II trial of a single infusion of third-party MSC post-kidney transplantation, in addition to standard immunosuppression. Ten kidney transplant recipients from deceased donors received third-party bone marrow MSCs (∼2 × 106/kg) on day 3 ± 2 post-transplant and were compared to 10 concurrent controls. No adverse effects were noted at MSC injection. One participant with a history of cardiac disease had a non-ST-elevation myocardial infarction approximately 3 hours after MSC infusion. Incidences of opportunistic infections and acute rejection were similar. At day 7 post-transplant, estimated glomerular filtration rate (eGFR) in MSC-treated recipients reached 48.6 ml/min/1.73m2, compared to 32.5 ml/min/1.73m2 in controls and 29.3 ml/min/1.73m2 in our overall cohort of kidney transplant recipients. No difference in eGFR was found at 1 year. MSC-treated recipients showed increased frequencies of regulatory T cells at day 30, with no significant change in B cell frequencies compared to concurrent controls. Four MSC-treated participants developed antibodies against MSC or shared kidney-MSC HLA, with only 1 with MFI >1500. A single infusion of third-party MSC following kidney transplantation appears to be safe, with one cardiac event of unclear relationship to the intervention. MSC therapy is associated with increased regulatory T cell proportion and with improved early allograft function. Long-term effects, including potential immunization against MSC, remain to be studied. SN - 1523-1755 UR - https://www.unboundmedicine.com/medline/citation/30528263/Infusion_of_third_party_mesenchymal_stromal_cells_after_kidney_transplantation:_a_phase_I_II_open_label_clinical_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0085-2538(18)30712-9 DB - PRIME DP - Unbound Medicine ER -