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Transplantation of Clinical Grade NSCs Shows Potential as a Huntington's Disease Treatment

Review of "Implantation of the clinical‐grade human neural stem cell line, CTX0E03, rescues the behavioral and pathological deficits in the quinolinic acid‐lesioned rodent model of Huntington's disease" from STEM CELLS by Stuart P. Atkinson

The replacement of the degenerated medium spiny neurons (MSNs) in the striatum and the modulation of pathogenic pathways via stem cell transplantation represents a potentially effective therapeutic approach to the treatment of Huntington's disease. In the hope of developing neural stem cell (NSC) transplantation into a clinically-relevant treatment for Huntington's disease, researchers led by Jihwan Song (Cha University, Gyeonggi‐do, South Korea) explored the potential of CTX0E03, a GMP‐manufactured conditionally immortalized human NSC line [1, 2] that has displayed promising results following direct intracerebral implantation into a rodent stroke model [1, 3, 4]. 

In their recent STEM CELLS article [5], Yoon et al. describe how the implantation of NSCs in a quinolinic acid (QA)-lesioned rat model of Huntington's disease [6, 7], which exhibits MSN loss and neuroinflammation, led to significant improvements in behavior and pathology via cell replacement and the induction of host cell regeneration.

The authors assessed behavioral changes after NSCs transplantation using the rotarod, stepping, and staircase tests and evaluated in vivo differentiation and neuronal connections via both immunohistochemical staining and retrograde tracing. Encouragingly, NSC transplantation induced significant behavioral improvements when compared to the control groups (sham and fibroblast transplanted) after 8 to 12 weeks. Immunostaining established that NSCs displayed neuroprotective abilities, via the expression of brain-derived neurotrophic factor (BDNF), and replaced lost cells through differentiation into DARPP‐32-positive medium spiny neurons and GABAergic neurons in the striatum and Tbr1‐positive neurons in the cortex at 13 weeks. Meanwhile, retrograde labeling highlighted stable engraftment and the connection of transplanted NSCs with host brain tissues. Furthermore, NSC transplantation also prompted the reduction in the formation of the glial scar by reducing astrocytic and microglial responses, dampened inflammation through the polarization of macrophages into the anti-inflammatory and pro-regenerative M2 phenotype, and induced both endogenous neurogenesis and angiogenesis.

Overall, the authors provide ample preclinical evidence for the utility of clinical‐grade NSCs in the treatment of Huntington's disease by establishing significant improvements in behavioral and pathological deficits through cell replacement and the induction of host cell regeneration mechanisms. The authors believe that these findings now support the clinical development of CTX0E03 for the treatment of human Huntington's disease patients.

For more on the future of NSC therapy for the treatment of Huntington's disease, stay tuned to the Stem Cells Portal!


  1. Stroemer P, Patel S, Hope A, et al., The Neural Stem Cell Line CTX0E03 Promotes Behavioral Recovery and Endogenous Neurogenesis After Experimental Stroke in a Dose-Dependent Fashion. Neurorehabilitation and Neural Repair 2009;23:895-909.
  2. Kalladka D, Sinden J, Pollock K, et al., Human neural stem cells in patients with chronic ischaemic stroke (PISCES): a phase 1, first-in-man study. The Lancet 2016;388:787-796.
  3. Hicks C, Stevanato L, Stroemer RP, et al., In Vivo and in Vitro Characterization of the Angiogenic Effect of CTX0E03 Human Neural Stem Cells. Cell Transplantation 2013;22:1541-1552.
  4. Sinden JD, Hicks C, Stroemer P, et al., Human Neural Stem Cell Therapy for Chronic Ischemic Stroke: Charting Progress from Laboratory to Patients. Stem Cells and Development 2017;26:933-947.
  5. Yoon Y, Kim HS, Jeon I, et al., Implantation of the clinical-grade human neural stem cell line, CTX0E03, rescues the behavioral and pathological deficits in the quinolinic acid-lesioned rodent model of Huntington's disease. STEM CELLS 2020;38:936-947.
  6. Lee S-T, Chu K, Park J-E, et al., Intravenous administration of human neural stem cells induces functional recovery in Huntington's disease rat model. Neuroscience Research 2005;52:243-249.
  7. Lelos MJ and Dunnett SB, Generating Excitotoxic Lesion Models of Huntington’s Disease, in Huntington’s Disease, S.V. Precious, A.E. Rosser, and S.B. Dunnett, Editors. 2018, Springer New York: New York, NY. p. 209-220.