title: Striatal Transplantation of Human Dopaminergic Neurons Differentiated From Induced Pluripotent Stem Cells Derived From Umbilical Cord Blood Using Lentiviral Reprogramming.
abstract: Human induced pluripotent stem cells (hiPSCs) are promising sources for regenerative therapies like the replacement of dopaminergic neurons in Parkinson's disease. They offer an unlimited cell source that can be standardized and optimized to produce applicable cell populations to gain maximal functional recovery. In the present study, human cord blood-derived iPSCs (hCBiPSCs) were differentiated into dopaminergic neurons utilizing two different in vitro protocols for neural induction: (protocol I) by fibroblast growth factor (FGF-2) signaling, (protocol II) by bone morphogenetic protein (BMP)/transforming growth factor (TGF-β) inhibition. After maturation, in vitro increased numbers of tyrosine hydroxylase (TH)-positive neurons (7.4% of total cells) were observed by protocol II compared to 3.5% in protocol I. Furthermore, 3 weeks after transplantation in hemiparkinsonian rats in vivo, a reduced number of undifferentiated proliferating cells was achieved with protocol II. In contrast, proliferation still occurred in protocol I-derived grafts, resulting in tumor-like growth in two out of four animals 3 weeks after transplantation. Protocol II, however, did not increase the number of TH(+) cells in the striatal grafts of hemiparkinsonian rats. In conclusion, BMP/TGF-β inhibition was more effective than FGF-2 signaling with regard to dopaminergic induction of hCBiPSCs in vitro and prevented graft overgrowth in vivo.
authors.affiliation: Institute of Neuroanatomy, Hannover Medical School, Hannover, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Effenberg
authors.forename: Nancy
authors.initials: N
authors.lastname: Stanslowsky
authors.forename: Alexander
authors.initials: A
authors.lastname: Klein
authors.forename: Maike
authors.initials: M
authors.lastname: Wesemann
authors.forename: Alexandra
authors.initials: A
authors.lastname: Haase
authors.forename: Ulrich
authors.initials: U
authors.lastname: Martin
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dengler
authors.forename: Claudia
authors.initials: C
authors.lastname: Grothe
authors.forename: Andreas
authors.initials: A
authors.lastname: Ratzka
authors.forename: Florian
authors.initials: F
authors.lastname: Wegner
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000502:physiology*; D003342:Corpus Striatum / Q000166:cytology; D059290:Dopaminergic Neurons / Q000166:cytology*; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D016086:Lentivirus / Q000378:metabolism; D017072:Neostriatum / Q000166:cytology; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000379:methods