Cell Replacement Strategies for Parkinson’s Disease

  • Diptaman Chatterjee
  • Dustin R. Wakeman
  • Jeffrey H. KordowerEmail author
Part of the Molecular and Translational Medicine book series (MOLEMED)


Since the 1970s, studies have evaluated the efficacy of cell transplantation therapy in neurological disorders, particularly in Parkinson’s disease. Parkinson’s is a progressive neurodegenerative disorder predominantly affecting midbrain, dopaminergic neurons along the nigrostriatal pathway. Abrogation of dopamine supply induces motor dysfunction and may play a role in other areas such as cognition and behavioral dysfunction. Current targeted treatments are effective in remediating motor symptoms, but elicit involuntary dyskinesia and off-target effects in the long term, warranting efforts toward the development of regionally specific therapies such as dopamine cell replacement. Thus far, provision of dopamine transmitting cells from fetal grafts has proven effective in animal models, suggested to be effective in open-label clinical trials, but has faltered in double-blind clinical assessments. Fetal grafts that survive greater than 10 years can be filled with Lewy bodies suggestive of a prion-like transmission from the host to the graft. Additionally, some patients develop novel graft-induced dyskinesias. Recent enhancements in stem cell technology have reinvigorated efforts toward cell replacement therapy using both embryonic stem cells and induced pluripotent stem cells. In the past 10 years, rapid advances in dopaminergic stem cell differentiation protocols, characterizations of nigrostriatal graft microenvironments, and effective transplantation in animal models have reinvigorated hope for potential clinical efficacy. However, cell replacement strategies will necessitate widespread, robust standardization of protocols and rigorously controlled clinical trials with careful subject selection before they are designated suitable for clinical use in Parkinson’s patients.


Parkinson’s disease Induced pluripotent stem cell Neural stem cells Neural grafting Cell transplantation Cell-based therapies Clinical trial Fetal tissue Dopamine 


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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Diptaman Chatterjee
    • 1
  • Dustin R. Wakeman
    • 2
  • Jeffrey H. Kordower
    • 1
    Email author
  1. 1.Department of Neurological SciencesRush University Medical CenterChicagoUSA
  2. 2.RxGen, Inc.SomervilleUSA

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