Preconditioned mesenchymal stem cells treat myasthenia gravis in a humanized preclinical model

• DOI: 10.1172/jci.insight.89665
• Publication Date: 2017-04-07T02:24:53Z
• Authors: Muriel Sudres; Marie Maurer; Marieke Robinet; Jacky Bismuth; Frédérique Truffault; Diane Girard; Nadine Dragin; Mohamed Attia; Elie Fadel; Nicola Santelmo; Camille Sicsic; Talma Brenner; Sonia Berrih-Aknin
• Keywords: Adult; Male; B-Lymphocytes; 0303 health sciences; [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology; Adolescent; Antibodies, Monoclonal; Mesenchymal Stem Cells; Mice, SCID; Mesenchymal Stem Cell Transplantation; Myasthenia Gravis, Autoimmune, Experimental; 3. Good health; Disease Models, Animal; Mice; Young Adult; 03 medical and health sciences; Mice, Inbred NOD; Animals; Heterografts; Humans; Female; Receptors, Cholinergic; Child; [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology

Myasthenia gravis (MG) with anti–acetylcholine receptor (AChR) Abs is an autoimmune disease characterized by severe defects in immune regulation and thymic inflammation. Because mesenchymal stem cells (MSCs) display immunomodulatory features, we investigated whether how vitro–preconditioned human MSCs (cMSCs) could treat MG disease. We developed a new humanized preclinical model subcutaneously grafting fragments into immunodeficient NSG mice (NSG-MG model). Ninety percent of the animals displayed anti-AChR serum, 50% MG-like symptoms that correlated loss AChR at muscle endplates. Interestingly, each mouse experiment recapitulated features patient. next demonstrated cMSCs markedly improved MG, reducing level serum restoring expression endplate. Resting had smaller effect. Finally, showed underlying mechanisms involved (a) inhibition cell proliferation, (b) B cell–related costimulatory molecules, (c) activation complement regulator DAF/CD55. In conclusion, this study shows preconditioning step promotes therapeutic effects via combined mechanisms, making promising strategy for treating potentially other diseases.