title: Efficient generation of dopamine neuron-like cells from skin-derived precursors with a synthetic peptide derived from von Hippel-Lindau protein.
abstract: Skin-derived precursors (SKPs) from mammalian dermis represent neural crest-related stem cells capable of differentiating into both neural and mesodermal progency. SKPs are of clinical interest because they serve as accessible autologous donor cells for neuronal repair for neuronal intractable diseases. However, little is known about the efficient generation of neurons from SKPs, and phenotypes of neurons generated from SKPs have been restricted. In addition, the neuronal repair using their generated neurons as donor cells has not been achieved. The von Hippel-Lindau protein (pVHL) is one of the proteins that play an important role during neuronal differentiation, and recently neuronal differentiation of neural progenitor cells by intracellular delivery of a synthetic VHL peptide derived from elongin BC-binding site has been demonstrated. In the present study, a synthetic VHL peptide derived from elongin BC-binding site was conjugated to the protein transduction domain (PTD) of HIV-TAT protein (TATVHL peptide) to facilitate entry into cells, and we demonstrate the efficient generation of cells with dopaminergic phenotype from SKPs with the intracellular delivery of TATVHL peptide, and characterized the generated cells. The TATVHL peptide-treated SKPs expressed neuronal marker proteins, particularly dopamine neuron markers, and also up-regulated mRNA levels of proneural basic helix-loop-helix factors. After the TATVHL peptide treatment, transplanted SKPs into Parkinson's disease (PD) model rats sufficiently differentiated into dopamine neuron-like cells in PD model rats, and partially but significantly corrected behavior of PD model rats. The generated dopamine neuron-like cells are expected to serve as donor cells for neuronal repair for PD.
authors.affiliation: Department of Neurosurgery, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Kubo
authors.forename: Tetsuhiko
authors.initials: T
authors.lastname: Yoshida
authors.forename: Nahoko
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Takaakira
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Toshiro
authors.initials: T
authors.lastname: Mimura
authors.forename: Takao
authors.initials: T
authors.lastname: Nishiguchi
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Higashida
authors.forename: Isao
authors.initials: I
authors.lastname: Yamamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kanno