Hypoimmune induced pluripotent stem cell-derived cell therapeutics treat cardiovascular and pulmonary diseases in immunocompetent allogeneic mice.
Proc Natl Acad Sci U S A
; 118(28)2021 07 13.
Article
in En
| MEDLINE
| ID: mdl-34244428
ABSTRACT
The emerging field of regenerative cell therapy is still limited by the few cell types that can reliably be differentiated from pluripotent stem cells and by the immune hurdle of commercially scalable allogeneic cell therapeutics. Here, we show that gene-edited, immune-evasive cell grafts can survive and successfully treat diseases in immunocompetent, fully allogeneic recipients. Transplanted endothelial cells improved perfusion and increased the likelihood of limb preservation in mice with critical limb ischemia. Endothelial cell grafts transduced to express a transgene for alpha1-antitrypsin (A1AT) successfully restored physiologic A1AT serum levels in mice with genetic A1AT deficiency. This cell therapy prevented both structural and functional changes of emphysematous lung disease. A mixture of endothelial cells and cardiomyocytes was injected into infarcted mouse hearts, and both cell types orthotopically engrafted in the ischemic areas. Cell therapy led to an improvement in invasive hemodynamic heart failure parameters. Our study supports the development of hypoimmune, universal regenerative cell therapeutics for cost-effective treatments of major diseases.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Cardiovascular Diseases
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Stem Cell Transplantation
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Induced Pluripotent Stem Cells
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Immunocompetence
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Lung Diseases
Limits:
Animals
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2021
Type:
Article