There is a great potential in the use of pluripotent stem cells as a source for cell therapies and also as a tool for modeling diseases and biological processes (such as cell differentiation, for example). However, one of the major challenges regarding their use is to obtain a large amount of cells, necessary for both cell therapy and other types of analysis, such as drug design. For instance, taking adult stem cell studies as reference, it is estimated to be needed more than 1 billion cells just to complete one clinical trial.
The problem remains on how to generate such amount of cells in the laboratory. With the commonly used techniques (the so-called "static plates”), we would need several people manipulating the cells, using thousands of plates, causing great variation from plate-to-plate and also increasing contamination risks.
In this project, we aim to expand cell production through the use of agitated systems, called bioreactors.
In 2009, we published our first work on pluripotent stem cells scale up ( Fernandes et al.). Using small beads (microcarriers) with adherent surface, which served to increase the culture area, and a bioreactor prototype, our system proved successful not only in achieving a large amount of uniformly cultured cells, but also lowered the costs of production.
Now, we seek to optimize this process. We are testing new types of microcarriers in different culture media and expanding the use of spinners for induced pluripotent cells and embryoid bodies. Moreover, the idea is to further expand to actual bioreactors, which will raise the number of cells produced by many orders of magnitude. The cells generated from the agitated systems will be employed in preclinical trials (in animal models) for neurodegenerative diseases like Parkinson's disease and spinal cord injury. The cells will also be distributed to several research centers of the Brazilian National Cell Therapy Network in order to catalyze the research and development with human embryonic stem cells and induced pluripotent cells in Brazil.
Publications in scale-up