Details

Autor(en) / Beteiligte

• Sundberg, Maria
• Bogetofte, Helle
• Lawson, Tristan
• Jansson, Johan
• Smith, Gaynor
• Astradsson, Arnar
• Moore, Michele
• Osborn, Teresia
• Cooper, Oliver
• Spealman, Roger
• Hallett, Penelope
• Isacson, Ole

Titel

Improved Cell Therapy Protocols for Parkinson's Disease Based on Differentiation Efficiency and Safety of hESC‐, hiPSC‐, and Non‐Human Primate iPSC‐Derived Dopaminergic Neurons

Ist Teil von

• Stem cells (Dayton, Ohio), 2013-08, Vol.31 (8), p.1548-1562

Ort / Verlag

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• The main motor symptoms of Parkinson's disease are due to the loss of dopaminergic (DA) neurons in the ventral midbrain (VM). For the future treatment of Parkinson's disease with cell transplantation it is important to develop efficient differentiation methods for production of human iPSCs and hESCs‐derived midbrain‐type DA neurons. Here we describe an efficient differentiation and sorting strategy for DA neurons from both human ES/iPS cells and non‐human primate iPSCs. The use of non‐human primate iPSCs for neuronal differentiation and autologous transplantation is important for preclinical evaluation of safety and efficacy of stem cell‐derived DA neurons. The aim of this study was to improve the safety of human‐ and non‐human primate iPSC (PiPSC)‐derived DA neurons. According to our results, NCAM+/CD29low sorting enriched VM DA neurons from pluripotent stem cell‐derived neural cell populations. NCAM+/CD29low DA neurons were positive for FOXA2/TH and EN1/TH and this cell population had increased expression levels of FOXA2, LMX1A, TH, GIRK2, PITX3, EN1, NURR1 mRNA compared to unsorted neural cell populations. PiPSC‐derived NCAM+/CD29low DA neurons were able to restore motor function of 6‐hydroxydopamine (6‐OHDA) lesioned rats 16 weeks after transplantation. The transplanted sorted cells also integrated in the rodent brain tissue, with robust TH+/hNCAM+ neuritic innervation of the host striatum. One year after autologous transplantation, the primate iPSC‐derived neural cells survived in the striatum of one primate without any immunosuppression. These neural cell grafts contained FOXA2/TH‐positive neurons in the graft site. This is an important proof of concept for the feasibility and safety of iPSC‐derived cell transplantation therapies in the future. STEM Cells 2013;31:1548–1562