Development of a transplant injection device for optimal distribution and retention of human induced pluripotent stem cellâderived cardiomyocytes.
J Heart Lung Transplant
; 38(2): 203-214, 2019 02.
Article
em En
| MEDLINE
| ID: mdl-30691596
ABSTRACT
BACKGROUND:
Induced pluripotent stem cell (iPSC)âbased regenerative therapy is a promising strategy for cardiovascular disease treatment; however, the method is limited by the myocardial retention of grafted iPSCs. Thus, an injection protocol that efficiently introduces and retains human iPSC-derived cardiomyocytes (hiPSC-CMs) within the myocardium is urgently needed. The objective of the present study was to develop a method to improve the retention of hiPSCs in the myocardium for cardiac therapy.METHODS:
We efficiently produced hiPSC-CM spheroids in 3-dimensional (3D) culture using microwell plates, and developed an injection device for optimal 3D distribution of the spheroids in the myocardial layer. Device biocompatibility was assessed with purified hiPSC-CM spheroids. Device effectiveness was evaluated in 10- to 15-month-old farm pigs (nâ¯=â¯15) and 5- to 24-month-old micro-minipigs (nâ¯=â¯20). The pigs were euthanized after injection, and tissues were harvested for retention and histologic analysis.RESULTS:
We demonstrated an injection device for direct intramyocardial transplantation of hiPSC-CM spheroids from large-scale culture. The device had no detrimental effects on cell viability, spheroid shape, or size. Direct epicardial injection of spheroids mixed with gelatin hydrogel into beating porcine hearts using this device resulted in better distribution and retention of transplanted spheroids in a layer within the myocardium than did conventional needle injection procedures.CONCLUSIONS:
The combination of the newly developed transplant device and spheroid formation promotes the retention of transplanted CMs. These findings support the clinical application of hiPSC-CM spheroidâbased cardiac regenerative therapy in patients with heart failure.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Miócitos Cardíacos
/
Transplante de Células-Tronco
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Células-Tronco Pluripotentes Induzidas
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Insuficiência Cardíaca
Tipo de estudo:
Guideline
/
Prognostic_studies
Limite:
Animals
/
Female
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Humans
Idioma:
En
Revista:
J Heart Lung Transplant
Ano de publicação:
2019
Tipo de documento:
Article