Cancer Mutations in 22% of Stem Cells: Concern for Regenerative Medicine – BNN Breaking

Cancer-Related Mutations Found in 22% of Human Pluripotent Stem Cells: A Cause for Concern in Regenerative Medicine

A recent study conducted by the Hebrew University of Jerusalem has raised significant concerns in the rapidly evolving field of regenerative medicine. The study, focusing on human pluripotent stem cells (hPSCs)known for their capacity to self-renew and differentiate into various human cell typeshas unearthed a disturbing revelation. A staggering 22% of hPSC samples were found to carry at least one cancer-related mutation. These cells, despite their remarkable potential for tissue regeneration, disease modeling, and drug discovery, might harbor hidden dangers.

The majority of these mutations, accounting for approximately 70%, were discovered to be acquired during cell propagation in culture. This finding emphasizes the need for increased vigilance in the use of stem cell derivatives in both research and clinical applications. It underscores the importance of regular evaluations of cell cultures to ensure accurate conclusions and safe therapeutic practices.

The research was led by Prof. Nissim Benvenistys laboratory at the Azrieli Center for Stem Cell and Genetic Research. The team used a bioinformatic algorithm to analyze over 2,200 samples from more than 140 different hPSC lines. The study, published in the esteemed Nature Biotechnology, found that the most common mutation was in the P53 gene, a well-known tumor suppressor.

The high prevalence of mutations poses a serious challenge to the safety standards in research and clinical applications. Moreover, these mutations affect not only the growth advantage in culture but also influence the cell fate transition during differentiation. This raises considerable concerns for the future direction of the field, particularly in clinical settings. The findings of the study merit urgent attention and pave the way for more comprehensive safety protocols in regenerative medicine.

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Cancer Mutations in 22% of Stem Cells: Concern for Regenerative Medicine - BNN Breaking

Oral Stem Cells Genome Map Revolutionizes Regenerative Medicine – Mirage News

Cambridge, Mass., Jan. 16, 2024 - A team of researchers from the ADA Forsyth Institute and University of North Carolina (UNC), Chapel Hill used single-cell transcriptomic analysis to successfully map dental pulp stem cells (DPSC) and periodontal ligament stem cells (PDLSC) and found remarkable differences between them. The study, which appeared in the Journal of Dental Research, provides the most detailed analysis of these stem cells to date, identifying the entire genome of the stem cells and their potential differentiation trajectories.

"Dental pulp and periodontal ligament stem cells both have the potential to develop into any type of cell in the body," explained ADA Forsyth Scientist, Alpdogan Kantarci, DDS, MSc, PhD who led the study with UNC biostatistician, Di Wu, PhD. "We wanted to discover how they were different and whether there were differences in their capacity to differentiate into other cell types."

The team discovered that both types of stem cells have seven different gene clusters, with different categories of genes reflecting different stages in the process of differentiation. Four of those gene clusters were similar when comparing the two types of stem cells. Three of the clusters were uniquely different. While PDLSC's were more like fibroblasts (cells that can become connective tissue) because of an increased proportion of certain clusters, DPSCs had higher differentiation potential and converted more easily into bone cells.

"This new information on the specific genetic composition and mechanisms of differentiation in dental pulp and periodontal ligament stem cells will generate a new era of work in regenerative medicine" said Dr. Kantarci. "We could potentially select a stem cell based on its distinct properties to create targeted regenerative dental tissue repair and other regenerative therapies."

ADA Forsyth scientists obtained the stem cells from extracted teeth without culturing them (unlike other studies of these stem cells) and sent them unfrozen to UNC for single-cell transcriptomic analysis. Meanwhile, they also took the same cells and differentiated them into known cell types such as fibroblasts (cells that can become connective tissue) and osteoblasts (bone cells). The team then used advanced bioinformatics to compare and document the capacity of the two populations of stem cells to differentiate into osteoblasts or fibroblasts. The results of the bulk RNA sequencing validated the findings of the single-cell transcriptomics.

"Prior to this study, people believed that stem cells were either very similar to each other, or very different from one another," said Dr. Kantarci. "Now we have enough information to see the huge potential for using specific features of these stem cells to create more effective and targeted regenerative therapies."

Additional collaborators on the project included T. Van Dyke, H. Hasturk, and Y.C. Wu of ADA Forsyth; Y. Yang, T. Alvarez, M.Z. Miao and G. Li of UNC Chapel Hill; and, J. Lou of University of Washington, Seattle.

Funding:

This work was funded by NIH/NIA (AG062496) and NIH/NIDCR (DE025020) grants, and the University of North Carolina Computation Medicine Program Award 2020. T. Alves holds a J. William Fulbright Scholarship (CAPESfinance code 001). M.Z. Miao is supported by the Intramural Research Program of the National Institutes of Health, National Institute of Dental and Craniofacial Research ZIA DE000719 and ZIE DE000727.

Paper cited:

"Single-Cell Transcriptomic Analysis of Dental Pulp and Periodontal Ligament Stem Cells," Journal of Dental Research. DOI: 10.1177/00220345231205283

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Oral Stem Cells Genome Map Revolutionizes Regenerative Medicine - Mirage News