Dataset Information

Therapeutic potential of clinical-grade human induced pluripotent stem cell-derived cardiac tissues.

ABSTRACT:

Objectives

To establish a protocol to prepare and transplant clinical-grade human induced pluripotent stem cell (hiPSC)-derived cardiac tissues (HiCTs) and to evaluate the therapeutic potential in an animal myocardial infarction (MI) model.

Methods

We simultaneously differentiated clinical-grade hiPSCs into cardiovascular cell lineages with or without the administration of canonical Wnt inhibitors, generated 5- layer cell sheets with insertion of gelatin hydrogel microspheres (GHMs) (HiCTs), and transplanted them onto an athymic rat MI model. Cardiac function was evaluated by echocardiography and cardiac magnetic resonance imaging and compared with that in animals with sham and transplantation of 5-layer cell sheets without GHMs. Graft survival, ventricular remodeling, and neovascularization were evaluated histopathologically.

Results

The administration of Wnt inhibitors significantly promoted cardiomyocyte (CM) (P < .0001) and vascular endothelial cell (EC) (P = .006) induction, which resulted in cellular components of 52.0 ± 6.1% CMs and 9.9 ± 3.0% ECs. Functional analyses revealed the significantly lowest left ventricular end-diastolic volume and highest ejection fraction in the HiCT group. Histopathologic evaluation revealed that the HiCT group had a significantly larger median engrafted area (4 weeks, GHM(-) vs HiCT: 0.4 [range, 0.2-0.7] mm² vs 2.2 [range, 1.8-3.1] mm²; P = .005; 12 weeks, 0 [range, 0-0.2] mm² vs 1.9 [range, 0.1-3.2] mm²; P = .026), accompanied by the smallest scar area and highest vascular density at the MI border zone.

Conclusions

Transplantation of HiCTs generated from clinical-grade hiPSCs exhibited a prominent therapeutic potential in a rat MI model and may provide a promising therapeutic strategy in cardiac regenerative medicine.

SUBMITTER: Osada H

PROVIDER: S-EPMC9390608 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

Therapeutic potential of clinical-grade human induced pluripotent stem cell-derived cardiac tissues.

Osada Hiroaki H Kawatou Masahide M Fujita Daiki D Tabata Yasuhiko Y Minatoya Kenji K Yamashita Jun K JK Masumoto Hidetoshi H

JTCVS open 20211001

<h4>Objectives</h4>To establish a protocol to prepare and transplant clinical-grade human induced pluripotent stem cell (hiPSC)-derived cardiac tissues (HiCTs) and to evaluate the therapeutic potential in an animal myocardial infarction (MI) model.<h4>Methods</h4>We simultaneously differentiated clinical-grade hiPSCs into cardiovascular cell lineages with or without the administration of canonical Wnt inhibitors, generated 5- layer cell sheets with insertion of gelatin hydrogel microspheres (GHM ...[more]

PMID: 36004071

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Dataset Information

Therapeutic potential of clinical-grade human induced pluripotent stem cell-derived cardiac tissues.

Objectives

Methods

Results

Conclusions

Publications

Therapeutic potential of clinical-grade human induced pluripotent stem cell-derived cardiac tissues.

Similar Datasets

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