Clinical-grade production and safe delivery of human ESC derived RPE sheets in primates and rodents

Autor: Walter Habeler, Marc Peschanski, Elena Brazhnikova, Olivier Goureau, José-Alain Sahel, Karim Ben M'Barek, Mohamed Jarraya, Alexandra Plancheron, Claire-Maëlle Fovet, Joanna Demilly, Christelle Monville, Stéphane Bertin, Ana Bejanariu, Céline Jaillard
Přispěvatelé: 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, Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), Institut de la Vision, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service MIRCEN (MIRCEN), Université Paris-Saclay-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), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Quinze-Vingts, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-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)-Université Paris-Saclay, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), ANR-16-CE17-0005,GENMSMD,Dissection génétique de la Susceptibilité Mendélienne aux infections mycobactériennes chez l'homme(2016), ANR-16-CE17-0008,SightREPAIR,Validation pré-clinique d'un épithélium pigmentaire rétinien dérivé de cellules souches embryonnaires humaines pour le traitement des rétinopathies(2016)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Pluripotent Stem Cells
Primates
Retinal degeneration
Biophysics
Rodentia
Bioengineering
Retinal Pigment Epithelium
02 engineering and technology
Gene mutation
Cell therapy
Biomaterials
03 medical and health sciences
Retinitis pigmentosa
medicine
Animals
Humans
Human pluripotent stem cells
[SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs
Induced pluripotent stem cell
[SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials
030304 developmental biology
0303 health sciences
Retinal pigment epithelium
business.industry
Age-related macular degeneration
Cell Differentiation
021001 nanoscience & nanotechnology
medicine.disease
eye diseases
3. Good health
Transplantation
medicine.anatomical_structure
RPE65
Mechanics of Materials
Ceramics and Composites
Cancer research
sense organs
0210 nano-technology
business
Stem Cell Transplantation
Zdroj: Biomaterials
Biomaterials, Elsevier, 2020, 230, pp.119603. ⟨10.1016/j.biomaterials.2019.119603⟩
Biomaterials, 2020, 230, pp.119603. ⟨10.1016/j.biomaterials.2019.119603⟩
ISSN: 0142-9612
Popis: International audience; Age-related macular degeneration as well as some forms of Retinitis Pigmentosa (RP) are characterized by a retinal degeneration involving the retinal pigment epithelium (RPE). Various strategies were proposed to cure these disorders including the replacement of RPE cells using human pluripotent stem cells (hPSCs), an unlimited source material to generate in vitro RPE cells. The formulation strategy of the cell therapy (either a reconstructed sheet or a cell suspension) is crucial to achieve an efficient and long lasting therapeutic effect. We previously developed a hPSC-RPE sheet disposed on human amniotic membrane that sustained the vision of rodents with retinal degeneration compared to the same cells injected as a suspension. However, the transplantation strategy was difficult to implement in large animals. Herein we developed two medical devices for the preparation, conservation and implantation of the hPSC-RPE sheet in nonhuman primates. The surgery was safe and well tolerated during the 7-week follow up. The graft integrity was preserved in primates. Moreover, the hPSC-RPE sheet did not induce teratoma or grafted cell dispersion to other organs in rodent models. This work clears the way for the first cell therapy for RP patients carrying RPE gene mutations (LRAT, RPE65 and MERTK).
Databáze: OpenAIRE
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