Regenerative Medicine

Staff List

Summary of Activity

Human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are attractive tools in regenerative medicine because of their unlimited self-renewal and unequivocal differentiation ability towards most somatic cell types. Our lab has a major focus in stem cell biology and its application, where we aim to provide novel therapies for refractory diseases.

Research Subject

• ? Preclinical transplantation study of ES or iPS cell-derived cardiomyocytes for cardiac repair
• ? Generation of stem cell-derived biological pacemakers for cardiac bradyarrhythmias
• ? Establishment of novel treatments for muscular dystrophy by combining cell and gene therapies

Outlook for Research

Despite the remarkable progress in medical technology, there are still many patients who suffer from refractory diseases that require organ replacement. Regenerative medicine is an attractive alternative therapy for this. Our mission in this field is to study stem cell biology and clarify the feasibility of using stem cells for organ repair to provide effective, life-changing treatments in the future.

Major Publications

1. Takemoto Y, Kadota S, Minami I, Otsuka S, Okuda S, Abo M, Punzalan LL, Shen Y, Shiba Y, Uesugi M.: Chemical Genetics Reveals a Role of Squalene Synthase in TGFβ Signaling and Cardiomyogenesis. Angew Chem Int Ed Engl. 60: 21824-21831, 2021.

2. Ichimura H, Kadota S, Kashihara T, Yamada M, Ito K, Kobayashi H, Tanaka Y, Shiba N, Chuma S, Tohyama S, Seto T, Okada K, Kuwahara K, Shiba Y.: Increased predominance of the matured ventricular subtype in embryonic stem cell-derived cardiomyocytes in vivo. Sci Rep. 10:11883, 2020.

3. Ogasawara T, Okano S, Ichimura H, Kadota S, Tanaka Y, Minami I, Uesugi M, Wada Y, Saito N, Okada K, Kuwahara K, Shiba Y.: Impact of extracellular matrix on engraftment and maturation of pluripotent stem cell-derived cardiomyocytes in a rat myocardial infarct model. Sci Rep. 7:8630, 2017.

4. Mao D, Ando S, Sato SI, Qin Y, Hirata N, Katsuda Y, Kawase E, Kuo TF, Minami I, Shiba Y, Ueda K, Nakatsuji N, Uesugi M.: A Synthetic Hybrid Molecule for the Selective Removal of Human Pluripotent Stem Cells from Cell Mixtures. Angew Chem Int Ed Engl. 56:1765-1770, 2017.

5. Ichimura H, Shiba Y.: Recent Progress Using Pluripotent Stem Cells for Cardiac Regenerative Therapy. Circ J. 81: 929-935, 2017.

6. Shiba Y, Gomibuchi T, Seto T, Wada Y, Ichimura H, Tanaka Y, Ogasawara T, Okada K, Shiba N, Sakamoto K, Ido D, Shiina T, Ohkura M, Nakai J, Uno N, Kazuki Y, Oshimura M, Minami I, Ikeda U.: Allogeneic transplantation of iPS cell-derived cardiomyocytes regenerates primate hearts. Nature. 538: 388-391, 2016.

7. Shiba N, Miyazaki D, Yoshizawa T, Fukushima K, Shiba Y, Inaba Y, Imamura M, Takeda S, Koike K, Nakamura A.: Differential roles of MMP-9 in early and late stages of dystrophic muscles in a mouse model of Duchenne muscular dystrophy. Biochim Biophys Acta. 1852: 2170-2182, 2015.

8. Gautam M, Fujita D, Kimura K, Ichikawa H, Izawa A, Hirose M, Kashihara T, Yamada M, Takahashi M, Ikeda U, Shiba Y.: Transplantation of adipose tissue-derived stem cells improves cardiac contractile function and electrical stability in a rat myocardial infarction model. J Mol Cell Cardiol. 81: 139-149, 2015

9. Shiba Y, Filice D, Fernandes S, Minami E, Dupras SK, Biber BV, Trinh P, Hirota Y, Gold JD, Viswanathan M, Laflamme MA.: Electrical Integration of Human Embryonic Stem Cell-Derived Cardiomyocytes in a Guinea Pig Chronic Infarct Model. J Cardiovasc Pharmacol Ther. 19:368-381, 2014

10. Shiba Y, Fernandes S, Zhu WZ, Filice D, Muskheli V, Kim J, Palpant NJ, Gantz J, Moyes KW, Reinecke H, Van Biber B, Dardas T, Mignone JL, Izawa A, Hanna R, Viswanathan M, Gold JD, Kotlikoff MI, Sarvazyan N, Kay MW, Murry CE, Laflamme MA.: Human ES-cell-derived cardiomyocytes electrically couple and suppress arrhythmias in injured hearts. Nature. 489: 322-325, 2012