Development of a Novel Therapy for Pheochromocytoma Using Patient-Derived iPS Cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K24010
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0905:Surgery of the organs maintaining homeostasis and related fields
• Research Institution: Kyoto University
• Principal Investigator: miyawaki yoshifumi 京都大学, 医学研究科, 研究員 (10844714)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: iPS cell / PPGL / 分化誘導 / 家族性腫瘍 / 副腎髄質

Outline of Final Research Achievements

We have established a new differentiation protocol that can induce iPS cell differentiation into adrenal medulla and paraganglia-like cells more rapidly and efficiently than previously reported differentiation induction protocols. The chromaffin cells generated by the new differentiation method showed a tendency to take up MIBG compared to undifferentiated iPS cells in vitro. The differentiated cells from healthy and patient-derived iPSCs were transplanted under the renal capsule of immunodeficient mice. Three months after transplantation, we evaluated the transplanted cells and found that both cells were considered to be chromaffin cells positive for CgA, TH, and FOX2B. The grafts derived from diseased iPSCs tended to increase in size compared to healthy iPSCs.

Free Research Field

iPS cell

Academic Significance and Societal Importance of the Research Achievements

褐色細胞腫・傍神経節細胞腫(以下PPGL)は副腎髄質または傍神経節のクロム親和性細胞から生じるカテコラミン産生を特徴とする神経内分泌腫瘍のひとつである。PPGLはカテコールアミン過剰により頭痛、発汗過多、発作的な血圧上昇、便秘、動悸に加えて、不安感、疲労感の原因となりQOLを低下させる。また良・悪性の診断が困難であり、悪性例は抗がん剤治療（CVD治療）、131I-MIBGがあるが、効果は限定的であり新規治療薬、治療法の開発が望まれている。本研究の成果である疾患iPSCをクロム親和性細胞に分化誘導する手法やそれを用いたXenograftによる疾患再現モデルは新規治療法の開発につながる。