The Potential of Induced Pluripotent Stem Cell (iPSC)-Derived Dopaminergic Neurons for Parkinson's Disease: A Systematic Review of Preclinical Studies

Abstract

Introduction: Parkinson's disease (PD) is a neurodegenerative disorder caused by the loss of midbrain dopaminergic (DA) neurons. Cell replacement therapy using iPSC-derived DA neurons offers a potential avenue for restoring lost function. This review evaluates the evidence from preclinical animal models regarding the efficacy, safety, and long-term viability of this approach.

Methods: A systematic search of PubMed, Web of Science, and Embase was performed for in-vivo studies using animal models of PD (e.g., 6-OHDA, MPTP) that were treated with iPSC-derived DA neurons. Outcomes of interest included behavioral recovery (e.g., rotation tests), survival and integration of grafted cells, and evidence of dopamine production.

Results: Thirty-four preclinical studies met the inclusion criteria. The majority of studies (85%) reported significant motor function improvement in rodent and non-human primate models following transplantation. Immunohistochemical analysis consistently showed graft survival, neuronal differentiation, and integration into the host striatum. Evidence of dopamine release from grafted cells was confirmed in over 70% of studies. However, 20% of studies reported the formation of non-neuronal tissue or teratomas, highlighting safety concerns.

Discussion: The preclinical evidence strongly supports the potential of iPSC-derived DA neurons to reverse motor deficits in animal models of PD. The primary challenges remain ensuring the purity of the transplanted cell population to avoid tumorigenicity and achieving standardized, scalable production of clinical-grade neurons.

Conclusion: Transplantation of iPSC-derived dopaminergic neurons is a highly promising strategy for Parkinson's disease, though significant safety and manufacturing hurdles must be overcome before widespread clinical application.