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Stem Cell Therapy for Parkinson's Disease - Which Cell is Best?

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Review of “Immature Midbrain Dopaminergic Neurons Derived from Floor-Plate Method Improve Cell Transplantation Therapy Efficacy for Parkinson’s Disease” from STEM CELLS Translational Medicine by Stuart P. Atkinson

The replacement of lost dopaminergic (DA)-neurons represents a potentially effective means to treat Parkinson's disease (PD); however, the question remains as to best source and type of cell. Human fetal cells have demonstrated some success in treating this devastating neurodegenerative disease [1], but ethical and practical concerns, as well as unfortunate side effects [2], limit this strategy. The production of DA-neurons from pluripotent stem cells (hPSCs) may serve as an effective strategy and studies regarding the transplantation of cells generated via the “floor-plate method” report promising results in animal models [3, 4].

To extend this technique, researchers from the laboratories of Eng King Tan (National Neuroscience Institute), Steve Oh (A*STAR), and Li Zeng (National Neuroscience Institute, Singapore) have now compared the in vivo engraftment capabilities of cells isolated from various stages of floor-plate differentiation to find out which cell is best for the job! The team’s new STEM CELLS Translational Medicine study now indicates that immature DA-neurons may be the most suitable cells for transplantation in PD therapy [5].

For their comparative study, Qiu et al. generated and transplanted three different types of neural cells differentiated from human embryonic stem cells (hESCs) employing the efficient floor-plate method: DA-progenitors differentiated for 16 days, immature DA-neurons differentiated for 25 days, and DA-neurons differentiated for 35 days. Following transplantation into a well-accepted PD mouse model, all three cell types exhibited high viability, little cell death, no signs of tumorigenic growth, and, importantly, the ability to differentiate/develop into mature DA-neurons. However, the mice receiving the immature DA-neurons (day 16) presented with the highest percentage of mature DA-neurons and this correlated to a higher level of behavioral functional recovery when compared to the DA-progenitors and the DA-neurons.

This exciting new systematic study highlights immature DA-neurons as the most promising cell type for hPSC-based therapeutic strategies for PD treatment, and the authors suggest that further characterization and scaled production may provide a consistent, effective, and safe means to battle this devastating neurological disease.

Will this paper soon lead to encouraging clinical results in the near future? Keep following the Stem Cells Portal to find out!

References

  1. Barker RA, Barrett J, Mason SL, et al. Fetal dopaminergic transplantation trials and the future of neural grafting in Parkinson's disease. Lancet Neurol 2013;12:84-91.
  2. Barker RA and Kuan WL. Graft-induced dyskinesias in Parkinson's disease: what is it all about? Cell Stem Cell 2010;7:148-149.
  3. Kriks S, Shim JW, Piao J, et al. Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson's disease. Nature 2011;480:547-551.
  4. Grealish S, Diguet E, Kirkeby A, et al. Human ESC-derived dopamine neurons show similar preclinical efficacy and potency to fetal neurons when grafted in a rat model of Parkinson's disease. Cell Stem Cell 2014;15:653-665.
  5. Qiu L, Liao MC, Chen AK, et al. Immature Midbrain Dopaminergic Neurons Derived from Floor-Plate Method Improve Cell Transplantation Therapy Efficacy for Parkinson's Disease. Stem Cells Transl Med 2017;6:1803-1814.