Soluble Microcarriers: Paving the Way for the Future of Regenerative Medicine Through More Efficient Cell Cultures

Regenerative medicine research has accelerated in recent years with the development of pluripotent stem cells, including embryonic stem (ES) cells and induced pluripotent stem (iPS) cells. These cells possess the ability to differentiate into various cell types with the same characteristics as those differentiated cells. This has the potential to lay the groundwork for innovative therapy that regenerates and repairs lost organs and bodily functions. For this reason, research is being conducted into the use of pluripotent stem cells to help treat various diseases related to the heart, nerves, cartilage, eyes, blood, and immune system.

Regenerative medicine began with cell sheets for the treatment of severe burns, which were approved in Japan in 2007. Currently, more than 10 items have been approved, but due to the time and effort required for cell culture, the treatment costs are significantly higher than those of conventional pharmaceuticals. Even under a high-cost medical care benefit system in Japan, it is not easily accessible in practice due to its high cost, and there is a need for more efficient methods of culturing cells in large quantities.

DNP and HDD have jointly developed a material to resolve this issue: Soluble microcarriers, which can improve operational efficiency and reduce costs through mass cultivation.

DNP has been focusing on developing new medical and healthcare-related businesses by utilizing its expertise in printing and information (P&I). It has developed a wide range of advanced solutions, such as a medication support service that enables remote monitoring of patients’ medication adherence, miniature three-dimensional (3D) intestinal models known as "intestinal organoids" for drug development applications, and an AI-assisted chest cancer screening reading system. In the field of regenerative medicine, DNP has participated in the Forum for Innovative Regenerative Medicine (FIRM) since its inception in 2011. It has also developed industry-academia partnerships, including running joint research courses at The University of Osaka for six years and Institute of Science Tokyo for over 10 years.

In 2020, DNP and HDD established a collaboration that combines DNP's expertise in microparticle surface processing technology and material selection with HDD's knowledge of cell culture technology for medical products and pharmaceutical regulatory compliance. The companies cooperated through each phase of development, including material selection, customer interviews, sample provision, and manufacturing process design, which led to the release of the soluble m in March 2023.

Cell culture methods can broadly be divided into two categories: suspension culture and adherent culture. Suspension culture refers to cells that proliferate while in a suspended state, like blood cells. Adherent culture refers to cells that adhere to a surface to proliferate, such as cells from muscle, skin, or cartilage. Attaching cells to microscopic particles called microcarriers can greatly improve the efficiency of adherent cell culture.

Comparison of adherent and suspension culture

Adherent culture usually involves attaching to containers like Petri dishes (two-dimensional culture). For example, culturing 100 million cells would require several hundred to several thousand containers, each needing periodic culture medium replacement. In addition, 10 to 20 incubators the size of small refrigerators would be required to store them.  By replacing these containers with microcarriers, cells can be cultured three-dimensionally within the medium. As a result, the same number of cells can be cultured in a container roughly the size of a 500 mL bottle. This dramatically reduces space requirements and also greatly improves the efficiency of operations such as culture medium replacement.

Space required for culturing 100 million cells

However, cultures grown with conventional plastic microcarriers generate microscopic fragments due to microcarrier collisions, which cannot be removed. For this reason, they have only been used to manufacture antibody drugs and vaccines, not for regenerative medicine, where cells are administered into the human body.

In contrast, the soluble microcarrier jointly developed by DNP and HDD uses cell dissociation reagents commonly employed in regenerative medicine. It dissolves only the microcarrier, allowing the cells to be easily collected without leaving behind any microscopic fragments. In addition, both the raw material and the cell dissociation reagentst have been shown to have low toxicity, making them highly biocompatible.

Cell culture workflow using soluble microcarriers

DNP's microcarriers have already been deemed suitable for use in the manufacture of regenerative medicine and other products by Japan’s Pharmaceuticals and Medical Devices Agency (PMDA), an independent administrative institution that reviews the quality, efficacy, and safety of pharmaceuticals. We are now making efforts to commercialize the product.

As the safety of soluble microcarriers is further demonstrated and the cost of cell-based medicines is reduced, we can expect to see a society in which regenerative medicine is available at local medical institutions. This means that regenerative medicine, previously accessible only at certain advanced medical facilities, will become available at core regional hospitals, with lower costs and insurance coverage. This could lead to the treatment of diseases that could not be treated in the past.

To realize this vision, several challenges must be addressed: further improving the efficiency of cell culture to reduce costs, verifying safety to reduce the risk of cultured cell alteration, and establishing a storage and distribution system to deliver cell-based medicines to the right place at the right time.

Clearing each of these challenges will require industry-wide collaboration, extending beyond the boundaries of individual companies, organizations, and research institutions. Based on the strong partnerships it has built with companies like HDD and academic institutions, DNP will continue to engage in a wide range of activities that broaden the scope of regenerative medicine. This includes providing soluble microcarriers to pharmaceutical manufacturers and taking on development contracts.

• The information in this article was accurate as of the publication date.