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
. 2025 Apr 20;52(1):404.
doi: 10.1007/s11033-025-10432-3.

Do human adipose stem cell-derived artificial insulin-producing cells develop tumorigenic characteristics throughout differentiation?

Parastoo Salehi Babadi  1 , Dian Dayer  2 , Mojtaba Jafarinia  1 , Mohsen Forouzanfar  1
Affiliations

Do human adipose stem cell-derived artificial insulin-producing cells develop tumorigenic characteristics throughout differentiation?

Parastoo Salehi Babadi et al. Mol Biol Rep. .

Abstract

Background: Artificial insulin-producing cells (IPCs) used to treat diabetes mellitus type 1 (DMT1) are naturally hampered by their carcinogenicity. This in vitro study aimed to examine the carcinogenic potential of IPCs produced by the differentiation of human adipose tissue-derived mesenchymal stem cells (hADSCs).

Methods and results: hADSCs were transformed into IPCs by administering insulin-transferrin, selenium (ITS), and nicotinamide in a 14-day differentiation protocol. The cells were transfected with 20 μg of pure Pdx1-pIRES recombinant vector on the tenth day of differentiation. The successful transfection was confirmed by Pdx1 overexpression and GFP fluorescence activity. The differentiated cells' capacity to release insulin and glucose-dependent C-peptide was used to evaluate their functionality. Gene expression was assessed using real-time PCR. Meanwhile, protein expression was investigated using western blotting. The transfected cells exhibited fluorescence activity and Pdx1 overexpression. The differentiated IPCs were able to secrete C-peptide and insulin. The artificial IPCs showed significantly reduced Oct4 and Nanog expression. However, the differentiation process induced a noticeable elevation in tPA expression. The artificial IPCs expressed much lower c-MYC expression compared to undifferentiated hADSCs. The differentiated cells exhibited a significant elevation in Glut2, MMP-2, CD24, P16, and P21 expression.

Conclusions: The differentiation technique used in this work produced functional beta-like cells devoid of typical markers of stem cells. The synthetic IPCs displayed characteristics of newly generated β-like cells. The artificial IPCs showed no signs of expressing tumor-associated markers. The findings imply that the artificial IPC cells lack tumor characteristics in vitro.

Keywords: Artificial insulin-producing cells; Differentiation; Human adipose tissue-derived mesenchymal stem cells; Tumor.

PubMed Disclaimer

Conflict of interest statement

Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: All protocols of the present study were approved by the research ethics committee of the Marvdasht Branch, Islamic Azad University, Marvdasht, Iran (IR.IAU.M.REC.1402.005).

Similar articles

See all similar articles

References

    1. Popoviciu MS, Kaka N, Sethi Y, Patel N, Chopra H, Cavalu S (2023) Type 1 diabetes mellitus and autoimmune diseases: a critical review of the association and the application of personalized medicine. J Pers Med- 13(3):422. https://doi.org/10.3390/jpm13030422 - DOI - PubMed - PMC
    1. Khin PP, Lee JH, Jun H-S (2023) Pancreatic beta-cell dysfunction in type 2 diabetes. Eur J Inflamm. https://doi.org/10.1177/1721727x231154152 - DOI
    1. Balboa D, Barsby T, Lithovius V, Saarimäki-Vire J, Omar-Hmeadi M, Dyachok O et al (2022) Functional, metabolic and transcriptional maturation of human pancreatic islets derived from stem cells. Nat Biotechnol 40(7):1042–1055. https://doi.org/10.1038/s41587-022-01219-z - DOI - PubMed - PMC
    1. Velazco-Cruz L, Song J, Maxwell KG, Goedegebuure MM, Augsornworawat P, Hogrebe NJ et al (2019) Acquisition of dynamic function in human stem cell-derived β cells. Stem Cell Rep 12(2):351–365. https://doi.org/10.1016/j.stemcr.2018.12.012 - DOI
    1. Pagliuca FW, Millman JR, Gürtler M, Segel M, Van Dervort A, Ryu JH et al (2014) Generation of functional human pancreatic β cells in vitro. Cell 159(2):428–439. https://doi.org/10.1016/j.cell.2014.09.040 - DOI - PubMed - PMC

MeSH terms

LinkOut - more resources