Development of process methods for large-scale culture of human embryonic stem cells and bio-engineered platforms that enhance cell proliferation and long-term survival of stem cell derived neurons

Human embryonic stem cells (hESCs), isolated from the inner cell mass of the blastocyst, are pluripotent and can give rise to any of the wide variety of specialized cells in the body. These cells can be expanded in culture for prolonged periods in defined serum free and feeder-free conditions in suspension and adherent cultures, while retaining the ability to produce various specified and functional cells, including neurons.
The recent progress in regenerative medicine indicates that these cells may hold great potential providing cellular models for drug development and screening, modelling diseases as well as aid in the development of future cell-based therapies for neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease. Crucial to the success of generating specialized cell populations, is an understanding of the mechanisms which influence the control of cell growth and differentiation by extrinsic and intrinsic factors. Nowadays, a limitation for the use of hESCs is the lack of proliferation methods in large scale.
The purpose of the present work will be to develop such methods. The work will be performed under a collaboration of the Animal Cell Technology Group, Div. of Bioproduction, KTH - Royal Institute of Technology and the Division of Alzheimer Neurobiology, Clinic of Geriatric Medicine, Karolinska University Hospital Huddinge. The knowledge and methods from animal cell cultivation processes of established cell lines will be applied to develop proliferation methods of hESCs in absence of feeder cells and serum in systems such as spinners or shake flasks, and to establish protocols with defined in vitro conditions which sustain the differentiation and survival of hESC-derived neural progenitors during prolonged periods.
Thus, the expected outcomes for this project will allow more reproducible culture conditions, facilitate scale-up and potentiate the clinical use of cells differentiated from hESC cultures.