Abstract |
Human adipose-derived stem cells (hASCs) have great potential as cell sources for the treatment of muscle disorders. To provide a safe method for the myogenic differentiation of hASCs, we engineered the MyoD protein, a key transcription factor for myogenesis. The engineered MyoD (MyoD-IT) was designed to contain the TAT protein transduction domain for cell penetration and the membrane-disrupting INF7 peptide, which is an improved version of the HA2 peptide derived from influenza. MyoD-IT showed greatly improved nuclear targeting ability through an efficient endosomal escape induced by the pH-sensitive membrane disruption of the INF7 peptide. By applying MyoD-IT to a culture, hASCs were efficiently differentiated into long spindle-shaped myogenic cells expressing myosin heavy chains. Moreover, these cells differentiated by an application of MyoD-IT fused to myotubes with high efficiency through co-culturing with mouse C2C12 myoblasts. Because internalized proteins can be degraded in cells without altering the genome, the myogenic differentiation of hASCs using MyoD-IT would be a safe and clinically applicable method.
|
Authors | Min Sun Sung, Ji-Young Mun, Ohsuk Kwon, Ki-Sun Kwon, Doo-Byoung Oh |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 437
Issue 1
Pg. 156-61
(Jul 19 2013)
ISSN: 1090-2104 [Electronic] United States |
PMID | 23810391
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright © 2013 Elsevier Inc. All rights reserved. |
Chemical References |
- MyoD Protein
- Peptides
- Recombinant Fusion Proteins
|
Topics |
- Adipose Tissue
(cytology)
- Amino Acid Sequence
- Animals
- Cell Differentiation
- Cell Nucleus
(metabolism)
- Coculture Techniques
- Humans
- Intracellular Space
(metabolism)
- Mice
- Molecular Sequence Data
- Muscle Development
- Muscle Fibers, Skeletal
(metabolism)
- MyoD Protein
(metabolism)
- Myoblasts
(cytology, metabolism)
- Peptides
(chemistry, metabolism)
- Protein Engineering
- Protein Transport
- Recombinant Fusion Proteins
(isolation & purification, metabolism)
- Solubility
- Stem Cells
(cytology, metabolism)
- Transduction, Genetic
|