MHC matching fails to prevent long-term rejection of iPSC-derived neurons in non-human primates

Autor: Susannah Williams, Alberto Nassi, Philippe Hantraye, Aurore Bugi, Marie Michael, Sophie Lecourtois, Caroline Jan, Emanuele Cozzi, Antoine Blancher, Anselme L. Perrier, Romina Aron Badin, Marta Vadori
Přispěvatelé: Service MIRCEN (MIRCEN), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut des cellules souches pour le traitement et l'étude des maladies monogéniques (I-STEM), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Généthon, Consorzio per la Ricerca sul Trapianto d'Organ = Consortium for Research in Organ Transplantation (CORIT), Azienda Ospedale Università di Padova = Hospital-University of Padua (AOUP), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Agence Nationale pour la Recherche HD-SCT French National Research Agency (ANR) [ANR-2010-RFSC-003], ANR-11-INBS-0011,NeurATRIS,Infrastructure de Recherche Translationnelle pour les Biothérapies en Neurosciences(2011), ANR-10-LABX-0073,REVIVE,Stem Cells in Regenerative Biology and Medicine(2010), European Project: 602245,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,REPAIR-HD(2013), Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Généthon-Université d'Évry-Val-d'Essonne (UEVE), Université Fédérale Toulouse Midi-Pyrénées, University Hospital of Padua, Consortium for Research in Organ Transplantation [Padua, Italy] (CORIT), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Centre National de la Recherche Scientifique (CNRS)-Service MIRCEN (MIRCEN), Transplantation Immunology Unit [Padua, Italy] (Department of Transfusion Medicine), University of Padua–Ospedale Giustinianeo [Padua, Italy], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Généthon, Hantraye, Philippe, Infrastructures - Infrastructure de Recherche Translationnelle pour les Biothérapies en Neurosciences - - NeurATRIS2011 - ANR-11-INBS-0011 - INBS - VALID, Laboratoires d'excellence - Stem Cells in Regenerative Biology and Medicine - - REVIVE2010 - ANR-10-LABX-0073 - LABX - VALID, Human pluripotent stem cell differentiation, safety and preparation for therapeutic transplantation in Huntington’s disease - REPAIR-HD - - EC:FP7:HEALTH2013-10-01 - 2017-09-30 - 602245 - VALID
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Cytotoxicity
Immunologic
Graft Rejection
Cytotoxicity
medicine.medical_treatment
[SDV]Life Sciences [q-bio]
Nude
MESH: Major Histocompatibility Complex / immunology
General Physics and Astronomy
Histocompatibility Testing
Disease
MESH: Cytotoxicity
Immunologic / immunology
Cell therapy
Major Histocompatibility Complex
0302 clinical medicine
Immunologic
MESH: Animals
lcsh:Science
Induced pluripotent stem cell
MESH: Rats
Nude
Neurons
Multidisciplinary
biology
Immune evasion
Immunogenicity
Immunosuppression
Cell Differentiation
Huntington's disease
MESH: Huntington Disease / immunology
MESH: Induced Pluripotent Stem Cells / transplantation
MESH: Transplantation
Autologous
3. Good health
[SDV] Life Sciences [q-bio]
MESH: Primates
Induced pluripotent stem cells
Huntington Disease
MESH: Neurons / immunology
Animals
Disease Models
Animal
Humans
Induced Pluripotent Stem Cells
Primates
Rats
Nude
Transplantation
Autologous
[SDV.IMM]Life Sciences [q-bio]/Immunology
MESH: Cell Differentiation / immunology
MESH: Huntington Disease / therapy
Autologous
[SDV.IMM] Life Sciences [q-bio]/Immunology
Science
MESH: Histocompatibility Testing
Major histocompatibility complex
General Biochemistry
Genetics and Molecular Biology
Article
MESH: Induced Pluripotent Stem Cells / cytology
03 medical and health sciences
medicine
[INFO.INFO-DL]Computer Science [cs]/Digital Libraries [cs.DL]
MESH: Neurons / transplantation
Transplantation
MESH: Humans
Animal
business.industry
MESH: Neurons / cytology
General Chemistry
Rats
030104 developmental biology
MESH: Graft Rejection / immunology
Disease Models
biology.protein
lcsh:Q
MESH: Disease Models
Animal
MESH: Induced Pluripotent Stem Cells / immunology
business
Neuroscience
030217 neurology & neurosurgery
Zdroj: Nature Communications
Nature Communications, In press, 10, pp.4357. ⟨10.1038/s41467-019-12324-0⟩
Nature Communications, Nature Publishing Group, 2019, 10, pp.4357. ⟨10.1038/s41467-019-12324-0⟩
Nature Communications, Vol 10, Iss 1, Pp 1-12 (2019)
ISSN: 2041-1723
DOI: 10.1038/s41467-019-12324-0⟩
Popis: Cell therapy products (CTP) derived from pluripotent stem cells (iPSCs) may constitute a renewable, specifically differentiated source of cells to potentially cure patients with neurodegenerative disorders. However, the immunogenicity of CTP remains a major issue for therapeutic approaches based on transplantation of non-autologous stem cell-derived neural grafts. Despite its considerable side-effects, long-term immunosuppression, appears indispensable to mitigate neuro-inflammation and prevent rejection of allogeneic CTP. Matching iPSC donors’ and patients’ HLA haplotypes has been proposed as a way to access CTP with enhanced immunological compatibility, ultimately reducing the need for immunosuppression. In the present work, we challenge this paradigm by grafting autologous, MHC-matched and mis-matched neuronal grafts in a primate model of Huntington’s disease. Unlike previous reports in unlesioned hosts, we show that in the absence of immunosuppression MHC matching alone is insufficient to grant long-term survival of neuronal grafts in the lesioned brain.
Matching iPSC donors’ and patients’ HLA haplotypes has been proposed as a way to generate cell therapy products with enhanced immunological compatibility. Here the authors show that MHC matching alone is insufficient to grant long-term survival of neuronal grafts in the lesioned brain of non-human primates.
Databáze: OpenAIRE
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