Generation of Midbrain Dopamine Neurons from Human ES Cells by Forced Expression of Lmx1a
Specification, Patterning, and Maintenance of Midbrain Dopam, 2006
Drs. Ericson and Perlmann have identified two key transcription factors (Lmx1a and Msx1) that regulate early development of dopamine neurons and can induce nearly 90% ‘authentic’ dopamine neurons when expressed in mouse embryonic stem cells. Using additional supplemental funding from MJFF, the team also demonstrated survival of these stem cell-derived dopamine neurons in rodent transplant studies; however, tumor formation is a problem. The team is working to solve this issue and to optimize the approach for use in human embryonic stem cells. MJFF has provided additional funding to keep this work focused on translating findings into human embryonic stem cell-based transplant approaches. Drs. Perlmann and Ericson, along with Dr. Anders Bjorklund, will optimize viral vector delivery of Lmx1a into human embryonic stem cells to determine whether this approach can enhance the yield of dopamine neurons. They will also test these Lmx1a-enhanced human embryonic stem cell-derived dopamine neurons in rodent transplants and look for ways to reduce potential tumor growth.
Dr. Ericson confirmed the ability of the factor Lmx1a to induce robust dopamine neuron production from human embryonic stem (hES) cells, although attempts to graft these hES cell-derived dopamine neurons continues to result in poor graft survival. The team is also working on strategies to sort hES cell-derived dopamine neurons to remove any potential tumor-causing cells.
Professor at Ludwig Institute for Cancer Research; Karolinska Institute
Professor of Histology at Lund University
Location: Lund, Sweden