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TOKYO & PALO ALTO, Calif.

Heartseed Inc. (“Heartseed”), a Tokyo-based biotechnology company developing iPSC-derived cardiomyocytes for heart failure and I Peace Inc. (“I Peace”), a leading GMP cell CDMO in Palo Alto, California, have collaborated to generate cardiomyocytes using multiple donor-derived iPS cell lines produced by I Peace and Heartseed’s proprietary cardiomyocytes differentiation and purification methods. As a result, Heartseed has successfully produced high-purity cardiomyocytes consistently from all iPS cell lines used in this study. This achievement marks a significant step forward in the realization of autologous cardiac regenerative medicine, which uses iPS cells obtained from the patient’s own cells.

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(Cardiac Troponin T: a marker of cardiomyocytes, the percentage of positive markers indicates the purity of the cardiomyocytes.) (Graphic: Business Wire)

[Significance of stable production of high-purity cardiomyocytes derived from iPS cells]

A major advantage of medical treatment using autologous iPS cells is that immunosuppressive agents are not necessary because no immune reaction occurs when cells are transplanted. However, the differentiation efficiency of iPS cells into target cells varies, and in order to efficiently produce cardiomyocytes from different donor-derived iPS cells, it is necessary to optimize the method of cardiomyocyte production for each iPS cell. This has been a hurdle to the realization of medical treatment using autologous iPS cells.

[Background of the study]

I Peace has developed a technology to simultaneously generate iPS cells from multiple donors for their personalized iPS cell banking service (MyPeace) and has been able to produce numerous clinical-grade iPS cells affordably and reliably.

Heartseed is developing HS-001 (open chest administration) and HS-005 (catheter administration), which are microtissues of highly purified cardiomyocytes (cardiomyocyte spheroids) generated from allogeneic iPS cells, and is accumulating know-how on the properties of cardiomyocytes and efficient methods of inducing cardiomyocyte differentiation.

In this context, Heartseed has been investigating the production of high-purity cardiomyocytes using multiple donor-derived iPS cell lines produced by I Peace, using Heartseed’s original method of cardiomyocyte differentiation and purification.

[Study results]

When a conventional cardiomyocyte differentiation method was applied, low differentiation efficiency was observed in many iPS cell lines (Figure 1). On the other hand, by applying Heartseed’s original cardiomyocyte differentiation method, high differentiation efficiency into cardiomyocytes was observed from all eight iPS cell lines with four different donors (Figure 2). Furthermore, by applying Heartseed’s proprietary purification method “Metabolic Selection*” to the obtained cardiomyocytes, nearly 99% purity was achieved in all eight lines, which is suitable for medical applications.

*Metabolic selection: a method that focuses on the differences in energy metabolism between cell types and obtains target cells selectively by removing essential components for the survival of non-target cells from the culture medium so that non-target cells are eliminated.

Heartseed and I Peace will continue to work towards establishing regenerative medicine using patients’ own iPS cells.

For details: https://www.heartseed.jp/en/index.html

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