Establishment of efficient and economical myocardial regeneration therapy using artificial G-CSF receptor.

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K20206
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 90120:Biomaterials-related
• Research Institution: Ritsumeikan University
• Principal Investigator: UEYAMA TOMOE 立命館大学, 総合科学技術研究機構, 研究員 (60844280)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 人工受容体 / 多能性幹細胞 / 分化

Outline of Final Research Achievements

It has been of great demand for cardiac regeneration therapy to produce sufficient number of cardiomyocytes from pluripotent stem cells. However, it remains challenging to efficiently differentiate cardiomyocytes with low costs. Granulocyte colony-stimulating factor (G-CSF) receptor (GCSFR) signaling is known to activate JAK/STAT signaling and enhance cardiac differentiation from pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells (iPSCs).
In the present study, we generated chimeric GCSFRs in which single chain Fv of anti-fluorescein (FL) antibody was ligated to transmembrane/cytoplasmic domains of GCSFR. As an inexpensive alternative ligand FL-conjugated, bovine serum albumin can bind to the chimeric GCSFRs, activate the JAK/STAT3 pathway, and enhance the efficiency of cardiac differentiation from iPSCs. This work could contribute to stem cell-based cardiac regeneration therapy as an economical and powerful strategy.

Free Research Field

再生医学

Academic Significance and Societal Importance of the Research Achievements

本研究では、人工受容体を用いて安全かつ効率的・経済的にiPS細胞から心筋細胞を作製する系を確立した。この人工受容体をiPS細胞へ安定発現させることで、安価な代替リガンド刺激により、心筋分化促進因子の一つG-CSFの細胞内シグナル伝達が制御可能となった。人工受容体の最大の特色と利点は、安価で入手し易くかつ生理活性のない分子をリガンドとして用いる点にある。代替リガンドの調整コストは、本来のリガンドである組換えG-CSFタンパク質に比較して、20分の1程度であり経済的な分化誘導を実現しており、この手法は他の受容体に対しても構築が可能で、広い汎用性から再生医療へ大きな貢献が期待される。