Assessment of a potential application of endogenous stem cells to treat congenital disorders

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20740
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0802:Biomedical structure and function and related fields
• Research Institution: Kobe University
• Principal Investigator: Sunardi Mukhamad 神戸大学, 医学研究科, 教育研究補佐員 (30961817)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: tissue regeneration / enteric nervous system / endogenous stem cell / Hirschsprung disease

Outline of Final Research Achievements

Many congenital diseases display incomplete organ development due to impaired function of stem cells caused by toxic effects of gene mutations. While surgery is a common treatment, their effects remain unsatisfactory. Advances in genome editing offer hope for correcting these mutations in stem cells, potentially aiding organogenesis. We used Hirschsprung disease as a model for congenital diseases, a condition where intestinal nerve cells are absent, often requiring surgery. To investigate if endogenous stem cells that reside within the affected body can restore themselves, we generated a mouse model with the disease in which the causative mutation can be conditionally removed or corrected. Correcting these stem cells resulted in increased cell proliferation and ameliorate the disease severity and also enhancing the gastrointestinal motility function. This research sheds light on potential utilization of endogenous stem cells for other congenital disorders.

Free Research Field

developmental biology and regenerative medicine

Academic Significance and Societal Importance of the Research Achievements

科学的には、私たちの研究は先天性疾患に影響を受ける組織を再生するための内因性幹細胞の潜在能力を明らかにしました。私たちは、Hirschsprung病の画期的なマウスモデルを開発し、標的変異修正を実証しました。社会的には、これにより先天性疾患に対する治療成果の向上が期待され、特に乳幼児におけるアガングリオノーシスなどの状態の予防が進んだ幹細胞療法が提供されます。