Stem cell therapy for Parkinson’s disease: where do we stand?
- 179 Downloads
A major neuropathological feature of Parkinson’s disease (PD) is the loss of nigrostriatal dopaminergic neuron. Patients exhibit motor symptoms, including bradykinesia, rigidity, and tremor. Neural grafting has been reported to restore striatial dopaminergic neurotransmission and induce symptomatic relief. The major limitation of cell replacement therapy for PD is the shortage of suitable donor tissue. The present review describes the possible sources of cells, including embryonic stem cells and somatic adult stem cells, both of which potentially could be used in cell therapy for PD, and discusses the advantages and disadvantages of each cell type.
KeywordsParkinson’s disease Neural grafting Embryonic stem cells Somatic adult stem cells
We thank Emma Lane for critical reading of the manuscript.
- Barberi T, Klivenyi P, Calingasan NY, Lee H, Kawamata H, Loonam K, Perrier AL, Bruses J, Rubio ME, Topf N, Tabar V, Harrison NL, Beal MF, Moore MA, Studer L (2003) Neural subtype specification of fertilization and nuclear transfer embryonic stem cells and application in parkinsonian mice. Nat Biotechnol 21:1200–1207CrossRefPubMedGoogle Scholar
- Björklund LM, Sanchez-Pernaute R, Chung S, Andersson T, Chen IY, McNaught KS, Brownell AL, Jenkins BG, Wahlestedt C, Kim KS, Isacson O (2002) Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proc Natl Acad Sci USA 99:2344–2349CrossRefPubMedGoogle Scholar
- Gross RE, Lombardi WJ, Hutchison WD, Narula S, Saint-Cyr JA, Dostrovsky JO, Tasker RR, Lang AE, Lozano AM (1999) Variability in lesion location after microelectrode-guided pallidotomy for Parkinson’s disease: anatomical, physiological, and technical factors that determine lesion distribution. J Neurosurg 90:468–477PubMedGoogle Scholar
- Kawasaki H, Suemori H, Mizuseki K, Watanabe K, Urano F, Ichinose H, Haruta M, Takahashi M, Yoshikawa K, Nishikawa S, Nakatsuji N, Sasai Y (2002) Generation of dopaminergic neurons and pigmented epithelia from primate ES cells by stromal cell-derived inducing activity. Proc Natl Acad Sci USA 99:1580–1585CrossRefPubMedGoogle Scholar
- Kitchens DL, Snyder EY, Gottlieb DI (1994) FGF and EGF are mitogens for immortalized neural progenitors. J Neurobiol 25:797–807Google Scholar
- Nakao N, Yokote H, Nakai K, Itakura T (2000) Promotion of survival and regeneration of nigral dopamine neurons in a rat model of Parkinson’s disease after implantation of embryonal carcinoma-derived neurons genetically engineered to produce glial cell line-derived neurotrophic factor. J Neurosurg 92:659–670PubMedGoogle Scholar
- Nishimura F, Yoshikawa M, Kanda S, Nonaka M, Yokota H, Shiroi A, Nakase H, Hirabayashi H, Ouji Y, Birumachi J, Ishizaka S, Sakaki T (2003) Potential use of embryonic stem cells for the treatment of mouse parkinsonian models: improved behavior by transplantation of in vitro differentiated dopaminergic neurons from embryonic stem cells. Stem Cells 21:171–180PubMedGoogle Scholar
- Ostenfeld T, Caldwell MA, Prowse KR, Linskens MH, Jauniaux E, Svendsen CN (2000) Human neural precursor cells express low levels of telomerase in vitro and show diminishing cell proliferation with extensive axonal outgrowth following transplantation. Exp Neurol 164:215–226Google Scholar
- Saucedo-Cardenas O, Quintana-Hau JD, Le WD, Smidt MP, Cox JJ, De Mayo F, Burbach JP, Conneely OM (1998) Nurr1 is essential for the induction of the dopaminergic phenotype and the survival of ventral mesencephalic late dopaminergic precursor neurons. Proc Natl Acad Sci USA 95:4013–4018CrossRefPubMedGoogle Scholar
- Shim JW, Koh HC, Chang MY, Roh E, Choi CY, Oh YJ, Son H, Lee YS, Studer L, Lee SH (2004) Enhanced in vitro midbrain dopamine neuron differentiation, dopaminergic function, neurite outgrowth, and 1-methyl-4-phenylpyridium resistance in mouse embryonic stem cells overexpressing Bcl-XL. J Neurosci 24:843–852CrossRefPubMedGoogle Scholar
- Wakitani S, Takaoka K, Hattori T, Miyazawa N, Iwanaga T, Takeda S, Watanabe TK, Tanigami A (2003) Embryonic stem cells injected into the mouse knee joint form teratomas and subsequently destroy the joint. Rheumatology (Oxford) 42:162–165Google Scholar