The Abnormal Proliferation of Midbrain Dopamine Cells From Human Pluripotent Stem Cells Is Induced by Exposure to the Tumor Microenvironment.

CNS Neurosci Ther

Department of Neurosurgery, Huashan Hospital, MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China.

Published: November 2024

AI Article Synopsis

  • The study addresses the issue of tumorigenicity in stem cell therapies, highlighting the need for more accurate testing methods beyond traditional animal models.
  • Researchers exposed midbrain dopamine (mDA) cells from human pluripotent stem cells to a tumor microenvironment by coculturing with medulloblastoma, observing increased proliferation in both lab and living models.
  • Findings suggest that this abnormal proliferation is linked to the activation of specific genetic pathways and cytokines, indicating that such exposure can improve tumorigenicity assessment methods.

Article Abstract

Aims: Tumorigenicity is a significant concern in stem cell-based therapies. However, traditional tumorigenicity tests using animal models often produce inaccurate results. Consequently, a more sensitive method for assessing tumorigenicity is required. This study aimed to enhance sensitivity by exposing functional progenitors derived from human pluripotent stem cells (hPSCs) to the tumor microenvironment (TME) in vitro before transplantation, potentially making them more prone to abnormal proliferation or tumorigenicity.

Methods: Midbrain dopamine (mDA) cells derived from hPSCs were exposed to the TME by coculturing with medulloblastoma. The cellular characteristics of these cocultured mDA cells were evaluated both in vitro and in vivo, and the mechanisms underlying the observed alterations were investigated.

Results: Our findings demonstrated increased proliferation of cocultured mDA cells both in vitro and in vivo. Moreover, these proliferating cells showed a higher expression of Ki67 and SOX1, suggesting abnormal proliferation. The observed abnormal proliferation in cocultured mDA cells was attributed to the hyperactivation of proliferation-related genes, the JAK/STAT3 pathway, and cytokine stimulation.

Conclusion: This study indicates that exposing functional progenitors to the TME in vitro before transplantation can induce abnormal proliferation, thereby increasing the sensitivity of tumorigenicity tests.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11576488PMC
http://dx.doi.org/10.1111/cns.70117DOI Listing

Publication Analysis

Top Keywords

abnormal proliferation
20
mda cells
16
cocultured mda
12
midbrain dopamine
8
cells
8
human pluripotent
8
pluripotent stem
8
stem cells
8
tumor microenvironment
8
tumorigenicity tests
8

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!