Significance: Cell therapy is expected to become an important method to treat chronic diseases such as diabetes, rheumatoid arthritis, retinal diseases like macular degeneration and certain types of cancers. The cell therapy market in general is projected to become a $200 billion industry by 2025. Human pluripotent stem cells (hPSCs) are of particular importance since their utility as a source for a variety of cell types for therapeutic use, extends to additional applications like tissue fabrication and drug screening. However, broad patient access is limited by the cost and capacity of cell manufacturing. Current technology, 3D suspension culture method, for cell production processes are complicated and can only produce cells for small patient populations at high cost. Additionally, culture conditions cause large variations of cell yield, compositions and potency. Consequently, patients receive highly varied cell products. Thus, there is a critical need for new technologies that have the capability to easily scale out, lower the cost of manufacturing and improve batch-to-batch repeatability. CellGro Technologies, LLC proposes a technology to address this critical need. The core technology, invented by Dr. Yuguo Lei, is a novel cell culturing method. Cells are cultured in hollow alginate tubes (AlgTubes) that are suspended in constantly refreshed cell culture medium. The alginate tubes create a protective micro-environment that favors rapid cell growth to high densities and high viability.
Specific Aims : The objective of this project is to develop the prototype of AlgTubes-based personalized bioreactor (PBR) that will generate optimized conditions for cell growth. The facilitating technology is a PBR which is loaded up to 20% (vol.) with the alginate tubes The PBR will use an internal circulation airlift design that utilizes sparged oxygen to circulate the medium to assure that the nutrient and oxygen demands are met for the cells in the alginate tubes.
In Specific Aim 1, we will design and build an AlgTube micro-extruder that extrudes multiple (up to six) tubes simultaneously. The extruder forms part of the disposable PBR system. The manufacture of the extruder requires precision machining and prototypes will be tested for tube uniformity across all six nozzles.
In Specific Aim 2, prototypes of the PBR will be built. Features include (apart from extruder) an airlift design to promote nutrient transport between the bulk and tube phases and easy cell harvesting. Most importantly, the PBR is a completely closed system.
In Specific Aim 3 we will evaluate the PBR prototypes performances. hPSCs will be cultured and cell densities and viability will be assessed. Overall impact: This project will advance the technology of cell manufacture and make cell therapy more broadly accessible by manufacturing products that are more consistent, reliable, and affordable.
Our goal is to develop a low-cost, disposable, personalized bioreactor (PBR) to automate production of consistent high-quality human pluripotent stem cells (hPSCs). Cell therapy is expected to become an important technology for the treatment of certain chronic diseases and hPSCs will play a major role, due to the ability to differentiate into many different cell types. However, scaling out manufacturing to large patient numbers with high consistency and at lower cost is still a challenge. The novel AlgTubes-based PBR cell expansion technology has the potential to set standards for consistent cell manufacturing and it will make cell therapy more accessible and affordable.
