1. Infusion of third-party mesenchymal stromal cells after kidney transplantation: a phase I-II, open-label, clinical study
- Author
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Hans Pottel, Gianni Maggipinto, Yves Beguin, Pauline Erpicum, Chantal Lechanteur, Céline Gregoire, François Jouret, Etienne Baudoux, Marie-Hélène Delbouille, Joan Somja, Alexandra Briquet, Olivier Detry, Catherine Bonvoisin, Frédéric Baron, and Laurent Weekers
- Subjects
Graft Rejection ,Male ,0301 basic medicine ,medicine.medical_specialty ,Regulatory T cell ,medicine.medical_treatment ,030232 urology & nephrology ,Urology ,Renal function ,Kidney ,Mesenchymal Stem Cell Transplantation ,T-Lymphocytes, Regulatory ,Cell therapy ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Transplantation, Homologous ,Lymphocyte Count ,Prospective Studies ,Kidney transplantation ,Aged ,Immunosuppression Therapy ,B-Lymphocytes ,business.industry ,Mesenchymal stem cell ,Immunosuppression ,Middle Aged ,Allografts ,medicine.disease ,Kidney Transplantation ,Transplantation ,Treatment Outcome ,030104 developmental biology ,medicine.anatomical_structure ,Nephrology ,Kidney Failure, Chronic ,Administration, Intravenous ,Female ,Bone marrow ,business ,Follow-Up Studies ,Glomerular Filtration Rate - 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.
- Published
- 2019
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