A 3D PRINTED BIOREACTOR ENABLES AUTOMATED AND SCALABLE MANUFACTURING OF MESENCHYMAL STEM CELLS (MSCS) AND MSC-DERIVED EXOSOMES

• Published in: Cytotherapy (Oxford, England) England), 2024-06, Vol.26 (6), p.e3-e4
• Main Authors: Ling, J., McMahon, N., Zimmern, K., Jung, J., Herzig, M.C., Zamilpa, R., D'souza, T., Christy, B.
• Format: Article
• Language: English
• Subjects: exosomes; manufacturing bioreactor; mesenchymal stem cells
• ISSN: 1465-3249; 1477-2566
• DOI: 10.1016/j.jcyt.2024.04.015

Current challenges in manufacturing of cell and gene therapies partly stem from limitations in commercially available cell expansion bioreactors. Traditional 2D cell culture devices like flasks, dishes, HyperPlate, CellFactory are manually operated with limited scalability and are prone to product variations and contamination. Automated and scalable adherent cell culture bioreactors, such as Pall's iCELLis system, deviate from traditional 2D monolayer cell culture, making it difficult to harvest cells and achieve high biologic yields. Automated and scalable suspension cell culture bioreactors, such as stirred tank bioreactors, are not suitable for shear-sensitive cells. Our goal is to develop an alternative bioreactor that transforms traditional 2D culture systems into automated and scalable bioreactor systems. We have been developing a patent-awarded 3D printed bioreactor (Figure 1a), which offers a low-shear and monolayer cell culture environment like traditional 2D cell culture devices. This makes it ideal for manufacturing cell and biologic products that are sensitive to cell culture environment (e.g., stem cells and exosomes). At the same time, this bioreactor facilitates an automatable, scalable, and closed manufacturing platform (Figure 1b) for cells and biologics, overcoming the limitations of the 2D culture system and providing products with low variations and cost reduction. Furthermore, this flexible bioreactor system is easy to scale (Figure 1c), suitable for both autologous and allogenic applications. Using our prototype system, we have demonstrated scalable expansion of human bone-marrow mesenchymal stem cells (MSCs) (Table 1), resulting in MSCs with comparable viability, identity, safety, and potency (including anti-inflammatory, T-cell suppression, and angiogenesis stimulation [Table 2]) to MSCs harvested from the control T-75 flasks. We have also shown scalable production of exosomes with consistent size distribution (Figure 2) and their ability to promote angiogenesis when incubated with human umbilical vein endothelial (HUVEC) cells (Figure 3). Our next step is to develop the prototype bioreactor system into an automated and scalable platform for evaluation by users, paving the way for commercialization.