Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Apr 28:16:1583391.
doi: 10.3389/fgene.2025.1583391. eCollection 2025.

Frontier progress and translational challenges of pluripotent differentiation of stem cells

Zhengbing Su  1 , Hui Dong  1 , Xiang Fang  1 , Wenli Zhang  1 , Hong Duan  1
Affiliations
Review

Frontier progress and translational challenges of pluripotent differentiation of stem cells

Zhengbing Su et al. Front Genet. .

Abstract

Stem cell research has significantly transformed regenerative medicine, with pluripotent stem cells (PSCs) serving as the cornerstone for disease modeling, drug screening, and therapeutic applications. Embryonic stem cells (ESCs) exhibit unparalleled self-renewal and tri-lineage differentiation, while induced pluripotent stem cells (iPSCs) bypass ethical constraints through somatic cell reprogramming. Clinical trials highlight the potential of mesenchymal stem cells (MSCs) in osteoarthritis and graft-versus-host disease, which leverage their immunomodulatory and paracrine effects. Despite advancements, challenges persist: iPSCs face epigenetic instability and tumorigenic risks, and adult stem cells struggle with inefficient differentiation. This paper systematically reviews stem cell source classification, differentiation regulatory mechanisms, cutting-edge technologies such as CRISPR/Cas9, and explores field-specific controversies (e.g., epigenetic stability of iPSCs) and future directions (e.g., integration of organoids and biomaterials). By analyzing current progress and challenges, it provides a multidimensional perspective for stem cell research.

Keywords: disease modeling; pluripotent stem cells; regenerative medicine; stem cell differentiation; stem cell therapy.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Schematic illustration of 3D co-culture-generated cardiac microspheres.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Aboul-Soud M. A. M., Alzahrani A. J., Mahmoud A. (2021). Induced pluripotent stem cells (iPSCs)—roles in regenerative therapies, disease modelling and drug screening. Cells 10, 2319. 10.3390/cells10092319 - DOI - PMC - PubMed
    1. Ai Z., Niu B., Yin Y., Xiang L., Shi G., Duan K., et al. (2023). Dissecting peri-implantation development using cultured human embryos and embryo-like assembloids. Cell Res. 33, 661–678. 10.1038/s41422-023-00846-8 - DOI - PMC - PubMed
    1. Al Shueili B., Dantas A., Mahe E., Chu T. H., Yang Y., Labit E., et al. (2025). Knockout of the ING5 epigenetic regulator confirms roles in stem cell maintenance and tumor suppression in vivo . PLoS ONE 20, e0313255. 10.1371/journal.pone.0313255 - DOI - PMC - PubMed
    1. Bhartiya D., Nagvenkar P., Sriraman K., Shaikh A. (2013). An overview of pluripotent stem cells. Pluripot. Stem Cells. 10.5772/55130 - DOI
    1. Blocklet D., Toungouz M., Berkenboom G., Lambermont M., Unger P., Preumont N., et al. (2010). Myocardial homing of nonmobilized peripheral-blood CD34+ cells after intracoronary injection. Stem Cells 24, 333–336. 10.1634/stemcells.2005-0201 - DOI - PubMed

LinkOut - more resources