Biology subjects

Nakajima, I.

Publications and source records attributed to Nakajima, I..

2 recordsLinked to original sources

bioRxiv2025

Derivation of human post-mitotic cardiomyocytes from tetraploid iPSCs

Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iPS-CMs) have great potential in regenerative medicine. However, iPS-CMs are immature and resemble fetal cardiomyocytes, restricting their application. Although fetal cardiomyocytes in the human heart lose their proliferative potential during maturation and become tetraploid, iPS-CMs cannot replicate this tetraploidization and remain immature. To overcome this problem, we fused diploid iPSCs to establish tetraploid iPSCs and differentiated them into cardiomyocytes (4N-iPS-CMs). We found that 4N-iPS-CMs had more similar gene expression profiles, mitochondrial amounts, contractile impedance, and resistance to a potassium blocker in post-mitotic cardiomyocytes than conventional iPS-CMs. In addition, we successfully generated 4N-iPS-CMs from two individuals to mix two different genetic backgrounds. Thus, we demonstrated a novel strategy for generating human post-mitotic cardiomyocyte-like cells by generating tetraploid iPSCs.

cell biology↗

bioRxiv2023

In Vivo Delivery of Therapeutic Molecules by Transplantation of Genome-Edited Induced Pluripotent Stem Cells

Human induced pluripotent stem cells (iPSCs) have already been used in transplantation therapies. Currently, cells from healthy people are transplanted into patients with diseases. With the rapid evolution of genome editing technology, genetic modification could be applied to enhance the therapeutic effects of iPSCs, such as the introduction of secreted molecules to make the cells a drug delivery system. Here, we addressed this possibility by utilizing a Fabry disease mouse model, as a proof of concept. Fabry disease is caused by the lack of -Galactosidase A (GLA). We previously developed an immunotolerant therapeutic molecule, modified -N-acetylgalactosaminidase (mNAGA). We confirmed that secreted mNAGA from genome-edited iPSCs compensated for the GLA activity in GLA-deficient cells using an in vitro co-culture system. Moreover, iPSCs transplanted into Fabry model mice secreted mNAGA and supplied GLA activity to the liver. This study demonstrates the great potential of genome-edited iPSCs secreting therapeutic molecules.

cell biology↗