PUBLICATION

Xenograft of human pluripotent stem cell-derived cardiac lineage cells on zebrafish embryo heart

Authors
Takahi, M., Taira, R., Onozuka, J., Sunamura, H., Kondow, A., Nakade, K., Nakashima, K., Sato, I., Hayashi, Y., Patra, C., Ohnuma, K.
ID
ZDB-PUB-230803-45
Date
2023
Source
Biochemical and Biophysical Research Communications   674: 190-198 (Journal)
Registered Authors
Patra, Chinmoy
Keywords
Human induced pluripotent stem cells (hiPSCs), Mesoderm cell, Xenograft model, Zebrafish
MeSH Terms
  • Animals
  • Cell Differentiation
  • Heterografts
  • Humans
  • Induced Pluripotent Stem Cells*/transplantation
  • Mammals
  • Myocytes, Cardiac
  • Transplantation, Heterologous
  • Zebrafish*
PubMed
37532637 Full text @ Biochem. Biophys. Res. Commun.
Abstract
Cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs) are a promising cell source for regenerative medicine and drug discovery. However, the use of animal models for studying human cardiomyocytes derived from hiPSCs in vivo is limited and challenging. Given the shared properties between humans and zebrafish, their ethical advantages over mammalian models, and their immature immune system that is rejection-free against xenografted human cells, zebrafish provide a suitable alternative model for xenograft studies. We microinjected fluorescence-labeled cardiac lineage cells derived from hiPSCs, specifically mesoderm or cardiac mesoderm cells, into the yolk and the area proximal to the outflow tract of the linear heart at 24 hours post-fertilization (hpf). The cells injected into the yolk survived and did not migrate to other tissues. In contrast, the cells injected contiguous with the outflow tract of the linear heart migrated into the pericardial cavity and heart. After 1 day post injection (1 dpi, 22-24 hpi), the injected cells migrated into the pericardial cavity and heart. Importantly, we observed heartbeat-like movements of some injected cells in the zebrafish heart after 1 dpi. These results suggested successful xenografting of hiPSC-derived cardiac lineage cells into the zebrafish embryo heart. Thus, we developed a valuable tool using zebrafish embryos as a model organism for investigating the molecular and cellular mechanisms involved in the grafting process. This is essential in developing cell transplantation-based cardiac therapeutics as well as for drug testing, notably contributing to advancements in the field of cardio-medicine.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping