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Novel Microcarrier Developed by SMART Researchers Improves Cell Manufacturing Performance for Cell Therapy

Researchers from the Singapore-MIT Alliance for Research and Technology (SMART) developed a gelatine-based microcarrier used in bioreactor-based cell manufacturing, which increases production of mesenchymal stem cells used for cell therapy.

Cell therapy and regenerative medicine have been lauded as promising treatment methods with near-miraculous potential for several years, and new developments in cell culture and cell manufacturing technology are bringing us closer to a reality where such treatments can be more accessible and applicable to a wide range of conditions.

Cell therapy refers to a form of treatment where living cells, such as immune cells or stem cells, are injected or implanted in patients. It is often used for immunotherapy or for the restoration of damaged tissues, such as in bone marrow transplantation. One major obstacle to cell therapy being widely available is the scale of manufacturing of therapeutic cells, as cell therapy requires large amounts of cells which are produced through carefully tailored cell culture methods that differ for each type of cell.

Researchers from the Critical Analytics for Manufacturing Personalized-Medicine (CAMP) Interdisciplinary Research Group (IRG) of the Singapore-MIT Alliance for Research and Technology (SMART) may have found a way to improve current manufacturing methods of anchorage-dependent cells. This could increase yields of therapeutic cells and ultimately lower the cost of cell therapy. Specifically, they developed a microcarrier used in bioreactor-based cell manufacturing of mesenchymal stromal cells (MSCs). The research was conducted in collaboration with researchers from SMART CAMP, the Massachusetts Institute of Technology (MIT), the National University of Singapore (NUS) and the City University of Hong Kong (CityU) and their work is due to be published in Biotechnology Journal.

MSCs are multipotent stromal (connective tissue) cells, which have the potential to differentiate into many different tissue types, thus they have the potential to be used in regenerative medicine. They have also been observed to secrete cytokines, growth factors and exosomes that are effective in other ways such as in immunomodulation and in the treatment of several other disease conditions. MSCs require an adherent surface to serve as a support in order to grow and divide, which is where the researchers’ newly developed microcarriers come into play.

Microcarriers are surface matrices with sizes typically ranging from 100 to 300 microns, to which adherent cells like MSCs can attach, forming cell-microcarrier complexes. They allow the cells to grow while suspended in growth medium, such as in stirred bioreactors. Their large surface area to volume ratio also increases the yield of cultured cells.

The researchers developed a dissolvable gelatine-based microcarrier, which is particularly advantageous when applied to therapeutic cell manufacturing since the microcarriers can be fully dissolved through enzymatic reactions. This facilitates the process of harvesting cells, which is another challenge in the production of therapeutic cells. Overall, these new microcarriers performed better than commercial microcarriers in terms of yield and reduction of cell loss during harvesting, while achieving similar performance in cell attachment efficiency and proliferation rate.

“Our study achieved over 90 percent harvest rate of cells grown on the gelatine microcarriers, which is significantly higher than the 50 to 60 percent harvest rate seen in current standards,” explained Dr Ng Ee Xien, who is the lead author of the paper. “Using gelatine microcarriers also achieved tight control over microcarrier dimensions (for example, microcarrier diameter and stiffness) that facilitate uniform environmental conditions for controlling consistent cell numbers per microcarrier.”

Besides an increase in yield and reduced cell loss, the new gelatine-based microcarriers also produced higher-quality cell cultures, which displayed more balanced differentiation performance.

According to Professor Krystyn J. Van Vliet, who is a co-author of the paper, Lead Principal Investigator at CAMP and also Professor of Materials Science and Engineering and Biological Engineering at MIT, “innovations in microcarriers will aid in the scalability of certain cell types such as mesenchymal stromal cells for cell-based therapy, including for regenerative medicine applications. Developing a microcarrier platform for MSC culture has been a key part for SMART CAMP’s understanding and managing the critical quality attributes of these cell therapy products. We hope our findings help bring about better, more efficient and scalable cell therapies with predictable therapeutic outcomes for multiple patient needs, and high harvesting efficiency of those potent cells.” [APBN]