再生医療部

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再生医療部とは

新医療研究開発センター再生医療部は学内の各領域における研究者及び臨床医チームと連携し、分野別研究部門や診療科の垣根を越えた共同研究開発体制を推進するため、2010年新たに設立された開発部門です。重要な使命として、近年発見された様々な臓器由来の体性幹細胞または人工的多能性幹（iPS）細胞の樹立精製技術を用いて、多くの難治性疾患に対する患者さん固有の細胞治療法を開発し、臨床応用まで結び付ける一連の基盤研究開発部門です。

臨床研究

再生医療部では2003年に発見された心臓内に存在する幹細胞を用いて、希少かつ難治性の各種小児心不全疾患に対して、臨床研究及び臨床治験を進めています。
2011～2013年にかけて、世界初の心臓内幹細胞自家移植療法のTICAP第1相臨床研究（左心低形成症候群14症例）を実施し、冠動脈内への細胞注入法の安全性を確立しました。引き続き2013～2016年にかけて本細胞治療法の有効性を確認するため、PERSEUS第2相ランダム化臨床研究（機能的単心室症34症例）を発表し、現在、小児心不全疾患に対する細胞治療法の薬事法承認を目指し、2016年から国内3施設において、APOLLON第3相臨床治験（機能的単心室症39症例）を登録実施中です。
また、2017年より小児拡張型心筋症に対する細胞治療法の臨床研究（TICAP-DCM第1相臨床研究）も登録実施中であり、国内各小児専門施設より本再生医療研究への参加者を募集中です。

橋渡し探索研究

各分野の研究部門及び診療科との共同研究で、疾患別ヒトiPS細胞の樹立による次世代再生医療への探索開発、臨床応用に向けた橋渡し研究支援と革新的な細胞治療法に関する臨床試験の設計立案を行う。

先端医療としての拠点形成

本部門の到達目標として、幹細胞について分子生物学、分子遺伝学、発生学といった多様な角度から焦点を当てた研究アプローチを行い、分野を超えた人材交流や情報交換を通じて若手の医学研究者を育成し、既存医療技術では治癒しえない各種臓器における重症疾患に対して新規治療法を見出すことで、新たな医療技術のブレークスルーと先端医療としての拠点形成を目指す。

主要論文

1. Hirai　K, Sawada　R, Hayashi T, Araki T, Nakagawa N, Kondo M, Yasuda K, Hirata T, Sato T, Nakatsuka Y, Yoshida M, Kasahara S, Baba K, Oh H; TICAP/PERSEUS Study Group. Eight-Year Outcomes of Cardiosphere-Derived Cells in Single Ventricle Congenital Heart Disease. J Am Heart Assoc. 2024 Nov 11:e038137.

2. Hirai K, Ousaka D, Fukushima Y, Kondo M, Eitoku T, Shigemitsu Y, Hara M, Baba K, Iwasaki T, Kasahara S, Ohtsuki S, Oh H. Cardiosphere-derived exosomal microRNAs for myocardial repair in pediatric dilated cardiomyopathy. Sci Transl Med. 2020;12: eabb3336.

3. Sano T, Ousaka D, Goto T, Ishigami S, Hirai K, Kasahara S, Ohtsuki S, Sano S, Oh H. Impact of Cardiac Progenitor Cells on Heart Failure and Survival in Single Ventricle Congenital Heart Disease. Circ Res. 2018;122:994-1005.

4. Oh H. Cell Therapy Trials in Congenital Heart Disease. Circ Res. 2017;120:1353-1366.

5. Ishigami S, Ohtsuki S, Eitoku T, Ousaka D, Kondo M, Kurita Y, Hirai K, Fukushima Y, Baba K, Goto T, Horio N, Kobayashi J, Kuroko Y, Kotani Y, Arai S, Iwasaki T, Sato S, Kasahara S, Sano S, Oh H. Intracoronary Cardiac Progenitor Cells in Single Ventricle Physiology: The PERSEUS (Cardiac Progenitor Cell Infusion to Treat Univentricular Heart Disease) Randomized Phase 2 Trial. Circ Res. 2017;120:1162-1173.

6. Ishigami S, Ohtsuki S, Tarui S, Ousaka D, Eitoku T, Kondo M, Okuyama M, Kobayashi J, Baba K, Arai S, Kawabata T, Yoshizumi K, Tateishi A, Kuroko Y, Iwasaki T, Sato S, Kasahara S, Sano S, Oh H. Intracoronary Autologous Cardiac Progenitor Cell Transfer in Patients with Hypoplastic Left Heart Syndrom: The TICAP Prospective Phase 1 Controlled Trial. Circ Res. 2015;116:653-64.

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Introduction of Center

Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital

MISSION

Department of Regenerative Medicine was established in the Center for Innovative Clinical Medicine to build on Okayama University Hospital’s leadership in stem cell science and to set the foundation for the creation of a new regenerative medicine.
A diverse group of leading stem cell researchers and physicians from across multiple disciplines is working collectively through the engagement between basic and clinical scientists aimed at biomedical translation of stem cell and regenerative medicine research on their disease-specific challenge. The overall goal is to translate stem cell biology into therapies that could revolutionize medicine with new treatments for a variety of human diseases.

Clinical Trials

Single ventricle physiology is a fatal congenital heart disease. Patients who have undergone a series of staged palliation remain at risk for the development of late-onset heart failure. Cardiosphere-derived cells have shown to reduce myocardial fibrosis and increase ventricular function in preclinical studies.
Following the TICAP prospective phase 1 and PERSEUS randomized phase 2 studies in 48 patients with functional single ventricle, the therapeutic efficacy is currently verified by 39 participants in APOLLON phase 3 randomized multicenter clinical trial for pharmaceutical approval. We also extend this cell therapy trial in patients with pediatric dilated cardiomyopathy from 2017 (TICAP-DCM study).
We organize clinical trials for patients with heart disease when the rationale is appropriately supported by translational and basic research. Facility for Translational Medicine (FTM) in Okayama University Hospital serves as the Stem Cell Clinical Trials Center. FTM will also provide services and support for all aspects of the human trials needed for government approval.

Stem Cell Research

The heart’s ability to repair itself is quite limited for the most common cardiac insults; however, there is hope that either adult or embryonic stem cell derivatives may be capable of repairing injured heart muscle. Stem cells represent a promising avenue for therapy for heart failure, and they are changing the paradigms for the understanding of cardiac homeostasis.
Research areas are aimed at gaining a better understanding of cardiac stem cells, purified from human heart muscle, that continue to function through life time, finding how to induce cardiac stem cells to undergo particular cell types, dissecting how the proliferation of stem cells and their progeny is regulated, and then apply these information to experimental models by providing the appropriate regenerative stimuli to endow greater regenerative capacity to the human heart.
In a recent breakthrough, researchers apply the reprogramming technology to create new stem cells as well as heart muscle cells directly from patients to study the diseases and investigate new treatments. Our commitment to innovation expands the research aim to explore how stem cells are created, the mechanisms by which they are regulated, and how they devolve into cardiac muscle cells directly. The ultimate goal is to translate this knowledge into dramatic new medical therapies through the development of personalized stem cell based therapies for a wide range of diseases.

Selected Publications

1. Hirai　K, Sawada　R, Hayashi T, Araki T, Nakagawa N, Kondo M, Yasuda K, Hirata T, Sato T, Nakatsuka Y, Yoshida M, Kasahara S, Baba K, Oh H; TICAP/PERSEUS Study Group. Eight-Year Outcomes of Cardiosphere-Derived Cells in Single Ventricle Congenital Heart Disease. J Am Heart Assoc. 2024 Nov 11:e038137.

2. Hirai K, Ousaka D, Fukushima Y, Kondo M, Eitoku T, Shigemitsu Y, Hara M, Baba K, Iwasaki T, Kasahara S, Ohtsuki S, Oh H. Cardiosphere-derived exosomal microRNAs for myocardial repair in pediatric dilated cardiomyopathy. Sci Transl Med. 2020;12: eabb3336.

3. Sano T, Ousaka D, Goto T, Ishigami S, Hirai K, Kasahara S, Ohtsuki S, Sano S, Oh H. Impact of Cardiac Progenitor Cells on Heart Failure and Survival in Single Ventricle Congenital Heart Disease. Circ Res. 2018;122:994-1005.

4. Oh H. Cell Therapy Trials in Congenital Heart Disease. Circ Res. 2017;120:1353-1366.

5. Ishigami S, Ohtsuki S, Eitoku T, Ousaka D, Kondo M, Kurita Y, Hirai K, Fukushima Y, Baba K, Goto T, Horio N, Kobayashi J, Kuroko Y, Kotani Y, Arai S, Iwasaki T, Sato S, Kasahara S, Sano S, Oh H. Intracoronary Cardiac Progenitor Cells in Single Ventricle Physiology: The PERSEUS (Cardiac Progenitor Cell Infusion to Treat Univentricular Heart Disease) Randomized Phase 2 Trial. Circ Res. 2017;120:1162-1173.

6. Ishigami S, Ohtsuki S, Tarui S, Ousaka D, Eitoku T, Kondo M, Okuyama M, Kobayashi J, Baba K, Arai S, Kawabata T, Yoshizumi K, Tateishi A, Kuroko Y, Iwasaki T, Sato S, Kasahara S, Sano S, Oh H. Intracoronary Autologous Cardiac Progenitor Cell Transfer in Patients with Hypoplastic Left Heart Syndrom: The TICAP Prospective Phase 1 Controlled Trial. Circ Res. 2015;116:653-64.