Next Article in Journal
Silencing Heat Shock Protein 27 Inhibits the Progression and Metastasis of Colorectal Cancer (CRC) by Maintaining the Stability of Stromal Interaction Molecule 1 (STIM1) Proteins
Previous Article in Journal
Stem Cells Derived from Lipoma and Adipose Tissue—Similar Mesenchymal Phenotype but Different Differentiation Capacity Governed by Distinct Molecular Signature
Article Menu

Export Article

Open AccessArticle
Cells 2018, 7(12), 261; https://doi.org/10.3390/cells7120261

Transfer of Synthetic Human Chromosome into Human Induced Pluripotent Stem Cells for Biomedical Applications

1
Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky Ave., St-Petersburg 194064, Russia
2
Division of Molecular and Radiation Biophysics, Petersburg Nuclear Physics Institute named by B.P. Konstantinov of National Research Centre “Kurchatov Institute”, Orlova Roscha 1, Gatchina 188300, Russia
3
Developmental Therapeutics Branch, National Cancer Institute, Bethesda, MD 20892, USA
4
Almazov National Medical Research Centre, 2 Akkuratova Str., St-Petersburg 197341, Russia
5
Max-Delbruck Center for Molecular Medicine, 10 Robert-Rössle-Straße, 13125 Berlin, Germany
6
Institute of Translational Biomedicine, St-Petersburg State University, 7-9, Universitetskaya nab., St-Petersburg 199034, Russia
*
Author to whom correspondence should be addressed.
Received: 7 November 2018 / Revised: 3 December 2018 / Accepted: 6 December 2018 / Published: 8 December 2018
(This article belongs to the Special Issue iPS Cells for Disease Modeling)
Full-Text   |   PDF [2817 KB, uploaded 10 December 2018]   |  

Abstract

AlphoidtetO-type human artificial chromosome (HAC) has been recently synthetized as a novel class of gene delivery vectors for induced pluripotent stem cell (iPSC)-based tissue replacement therapeutic approach. This HAC vector was designed to deliver copies of genes into patients with genetic diseases caused by the loss of a particular gene function. The alphoidtetO-HAC vector has been successfully transferred into murine embryonic stem cells (ESCs) and maintained stably as an independent chromosome during the proliferation and differentiation of these cells. Human ESCs and iPSCs have significant differences in culturing conditions and pluripotency state in comparison with the murine naïve-type ESCs and iPSCs. To date, transferring alphoidtetO-HAC vector into human iPSCs (hiPSCs) remains a challenging task. In this study, we performed the microcell-mediated chromosome transfer (MMCT) of alphoidtetO-HAC expressing the green fluorescent protein into newly generated hiPSCs. We used a recently modified MMCT method that employs an envelope protein of amphotropic murine leukemia virus as a targeting cell fusion agent. Our data provide evidence that a totally artificial vector, alphoidtetO-HAC, can be transferred and maintained in human iPSCs as an independent autonomous chromosome without affecting pluripotent properties of the cells. These data also open new perspectives for implementing alphoidtetO-HAC as a gene therapy tool in future biomedical applications. View Full-Text
Keywords: human artificial chromosome (HAC); alphoidtetO-HAC; induced pluripotent stem cells (iPSCs); microcell-mediated chromosome transfer (MMCT); cell reprogramming human artificial chromosome (HAC); alphoidtetO-HAC; induced pluripotent stem cells (iPSCs); microcell-mediated chromosome transfer (MMCT); cell reprogramming
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Sinenko, S.A.; Skvortsova, E.V.; Liskovykh, M.A.; Ponomartsev, S.V.; Kuzmin, A.A.; Khudiakov, A.A.; Malashicheva, A.B.; Alenina, N.; Larionov, V.; Kouprina, N.; Tomilin, A.N. Transfer of Synthetic Human Chromosome into Human Induced Pluripotent Stem Cells for Biomedical Applications. Cells 2018, 7, 261.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cells EISSN 2073-4409 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top