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A. Kirkeby - Dopaminergic neurons


Dr. Agnete Kirkeby
Postdoc at Lund University, Lund, Sweden


Efficient production of hESC-derived dopaminergic progenitors under GMP conditions for treatment of Parkinson’s Disease


Parkinson’s Disease (PD) is a progressive and debilitating neurodegenerative disease to which we currently have no cure or disease-modifying treatment. The disease involves loss of dopaminergic (DA) neurons in the Substantia Nigra of the midbrain, and cell replacement therapy to replenish the lost neurons is regarded as a promising strategy to treat the disease. Significant progress has been made in recent years in developing protocols for production of transplantable DA progenitor cells from pluripotent cell sources. We and others have shown that upon transplantation to the brain, such progenitor cells can develop into mature DA neurons and reverse motor symptoms in animals models of PD. The big hurdle now remains to transfer these protocols to GMP standards, including also replacing coating material to GMP-compliant products in order to bring the stem cells the last step towards the clinic. Here, we developed a protocol for neuralising hESCs directly from day 0 of differentiation with GMP-compliant matrix, media and growth factors. This approach not only enables us to get highly pure populations of DA progenitor cells (>90%), but it also increases our final yield of transplantable cells >40 times when compared to previous embryoid body protocols starting with the same number of cells. This means that we are now able to produce around 2*109 DA progenitor cells starting from just a single 6-well plate of undifferentiated hESCs and this is in a scale suitable for clinical production.


Dr Agnete Kirkeby's resume