July 16,2020

I Peace, Inc. (CEO: Koji Tanabe, https://ipeace.com/), a Palo Alto-based biotech startup focusing on Nobel Prize-wining technology of induced pluripotent stem cells (iPSCs) has successfully developed a novel system to mass manufacture clinical-grade iPSCs for cell therapy in a palm-size closed cassette. The system was developed in collaboration with FANUC CORPORATION (Head Office: Oshino, Yamanashi Prefecture, Japan; CEO: Kenji Yamaguchi). The technology is modular and scalable with a small footprint, paving the way for simultaneous mass production of clinical-grade iPSCs from a multitude of donors in a single facility. 

Closed Automatic iPSC Mass Manufacturing System

Induced pluripotent stem cells (iPS cells or iPSCs) are stem cells induced from somatic cells that are reprogrammed to an embryonic stem cell-like state by introducing special factors (genes). iPSCs are able to become any type of cells in the body and proliferate almost indefinitely, like an embryonic stem cell. Unlike embryonic stem cells, iPSCs can be made from matured cells in the body, such as skin or blood cells, from anyone. iPSCs-derived cell therapy generated from a patient's own cells minimizes the risk of immune rejection. It is expected to change the course of regenerative medicine, drug discovery, and personalized medicine. 

Unlike other stem cells such as mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs), iPSCs can differentiate into all tissue and cell types, can be made with a small amount of cells, and can be grown to quantities necessary. These unique abilities make iPSCs unrivaled as stem cells of choice for patient-specific cell therapy and drug discovery.  For example, COVID19/SARS-CoV-2-targeted lung cells, differentiated from patient-derived iPSCs, are a valuable in vitro disease model and can be used for drug and vaccine discovery for SARS-CoV-2.

There are numerous ongoing preclinical and clinical studies involving iPSCs for diseases such as age-related macular degeneration, spinal cord injury, heart failure, GvHD, etc. with several of them yielding positive results.  However, the manufacturing of high quality, clinical-grade iPSCs currently faces a bottleneck. The iPSCs used in the first clinical trial in Japan cost approximately one million USD and took one year to generate.  At this cost and the rate of production, personalized stem cell-based medicine would not be practical.

I Peace's novel methodology to manufacture clinical-grade iPSCs in an automated closed, compact, and modular device provides the scalability required for mass parallel production of personalized clinical-grade iPSC lines within the I Peace GMP facility. I Peace will shortly begin gradually increasing its production capability while carefully examining logistical issues associated with mass production of iPSCs. This technology enables dramatic cost reduction and efficient production of clinical-grade iPSCs from multiple donors at the same time, paving the way for a future of global personalized stem cell-based medicine. 

Background on the development of the Fully Closed Automatic iPSC Mass Manufacturing System 

Existing methods of iPSC generation are labor and cost-intensive, with low efficiency. Clinical-grade iPSC manufacturing requires exclusive use of a whole clean room for just one donor over a long period of time, which meant that mass production was not practical and the associated cleanroom costs were enormous. This is a large barrier in making iPSC-derived medical treatments available to all. 

Due to these factors, it was challenging to efficiently mass-produce iPSCs from multiple donors. As a result, only a limited number of clinical-grade iPSC lines were available, with their very high cost as barrier to widespread use, up until now.  

Outline of the device

The fully closed automated iPSC manufacturing system that I Peace has successfully developed is different from an automated iPSC culturing system, which simply grows the iPSCs generated elsewhere. Instead, our compact closed-system is capable of reprogramming—carrying out the full sequence of processes required to change the cell fate of donor cells into iPSCs. The device carries no risk of cross-contamination between donors or from outside. Being modular and scalable with a small footprint, many units can be operated in parallel to carry out mass production of clinical-grade iPSCs from a large number of donors simultaneously in a single room. The whole system—from the individual biological steps to the overall operation—is automated, and the joint development project with FANUC CORPORATION included the creation of an automated operating system using robots.

This technology will revolutionize both allogeneic and personalized regenerative medicine. Unclogging the bottleneck of a limited number of available clinical-grade iPSC lines, this technology will allow us to offer researchers and institutions a steady supply of different clinical-grade iPSC lines from which they can select the iPSC line(s) best suited for their particular area of clinical research. This will be game-changing in accelerating the pace of clinical research using iPSCs. Additionally, the system's ability to simultaneously produce iPSCs from different donors makes personalized medicine possible. The technology will also accelerate drug discovery. Whereas up until now, drug discovery and regenerative medicine research have relied on a limited number of disease-specific iPSC lines, it will now be possible to prepare large libraries of iPSCs from patients and healthy individuals, which we believe will lead to faster discovery of better drugs.  

Adopting as its motto 'Peace of mind with iPSCs,' I Peace, Inc. has been working to create a world in which iPSC-based medical treatments are available to everyone. The closed-system automated iPSC production device makes iPSC mass production at dramatically reduced cost possible, which represents a great step forward toward a world where iPSC treatments are available to everyone. 

Going forward, the demand for iPSCs is expected to grow further as research progresses into regenerative medicine, new drug development, and a wide variety of other areas where iPSCs are utilized. To meet the iPSC demand expected in areas such as cell therapy, drug discovery research, and clinical trials, I Peace is working to have the system up and running by the end of 2020. I Peace is committed to working towards our vision of a future where each person has their own iPSCs banked for immediate use when necessary.

Supporting Information

Key Takeaways:

The device is capable of handling the entire iPSC generation process—starting from blood to frozen vials of iPSCs—not merely amplifying iPSCs prepared elsewhere.  

The device is compact, space-saving, and modular. It can be scaled up or down as necessary, making mass production of clinical-grade iPSCs possible. 

Due to its closed and compact nature, iPSCs can be produced simultaneously from a multitude of donors. 

Increasing the number of clinical-grade iPSC lines available will further promote clinical research into allogeneic transplant using iPSCs as well. 

The development is a major contribution to iPSC manufacturing cost reduction.