Open AccessHypoimmune induced pluripotent stem cell–derived cell therapeutics treat cardiovascular and pulmonary diseases in immunocompetent allogeneic mice
Author(s) -
T. Deuse,
Grigol Tediashvili,
Xiaomeng Hu,
Alessia Gravina,
Annika Tamenang,
Dong Wang,
Andrew J. Connolly,
Christian Mueller,
Beñat Mallavia,
Mark R. Looney,
Malik Alawi,
Lewis L. Lanier,
Sonja Schrepfer
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2022091118
Subject(s) - immunogenicity , immune system , genetic enhancement , cell therapy , stem cell , induced pluripotent stem cell , medicine , immunosuppression , cell , disease , immunology , clinical trial , computational biology , bioinformatics , biology , gene , pathology , microbiology and biotechnology , embryonic stem cell , genetics
Significance Precise gene editing allows engineering of immune receptors and ligands to reduce the immunogenicity of cells, and strategies for the generation of immune-evasive stem cell sources are currently being developed. This article describes the translational aspect of generating universally transplantable, disease-specific, therapeutic cell products. We provide proof of concept that immune-engineered cells can treat major cardiovascular and pulmonary diseases in fully allogeneic subjects without utilizing any immunosuppression. The translational aspect is emphasized by showing improvements in clinically relevant outcome measures, which are widely used in human trials. Depending on the feasibility of large-scale manufacturing of universal cell therapeutics, this approach could enable cost-effective cell therapy.