Human midbrain dopamine neurons transplanted into the nigra were able to be specifically projected to the dorsal striatum. These and other findings in a recent study in the Cell Stem Cell journal indicate the potential of using specialized neuronal types from stem cells to repair the neural circuit, addressing conditions such as Parkinson disease (PD).
The researchers transplanted hESC-derived midbrain dopamine (mDA) or cortical glutamate neurons into the substantia nigra or striatum of a PD model mouse.
When they implanted the mDA neurons into the PD model mouse, the researchers found extensive graft integration with host circuitry. The hESC-derived mDA neurons display A9 characteristics and restore functionality of the reconstructed nigrostriatal circuit to mediate improvements in motor function.
“These results indicate similarity in cell-type-specific pre- and post-synaptic integration between transplant-reconstructed circuit and endogenous neural networks, highlighting the capacity of hPSC-derived neuron subtypes for specific circuit repair
and functional restoration in the adult brain,” the researchers wrote.
“It is critical to transplant highly enriched, appropriately fated neural progenitors to achieve reconstruction of specific circuits for therapeutic outcomes,” the researchers concluded. “Most major neural cell types can now be generated efficiently from hESCs…Hence, cell-based therapy to treat neurological conditions is realistic.”
Xiong M, Tao Y, Gao Q, et al. Human stem cell-derived neurons repair circuits and restore neural function. Cell Stem Cell. 2020 Sep 16:S1934-5909(20)30410-0. doi: 10.1016/j.stem.2020.08.014