The Genetically Modified Polysialylated Form of Neural Cell Adhesion Molecule-Positive Cells for Potential Treatment of X-Linked Adrenoleukodystrophy.
10.3349/ymj.2013.54.1.246
- Author:
Jiho JANG
1
;
Han Soo KIM
;
Joon Won KANG
;
Hoon Chul KANG
Author Information
1. Department of Physiology, Yonsei University College of Medicine, Seoul, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
X-linked adrenoleukodystrophy;
polysialylated form of the neural cell adhesion molecule cells;
3,3',5-Triiodo-L-thyronine;
ABCD2 gene
- MeSH:
ATP-Binding Cassette Transporters/*metabolism;
Adrenoleukodystrophy/genetics/*therapy;
Animals;
Animals, Newborn;
Bromodeoxyuridine;
Cell Differentiation;
Fibroblast Growth Factor 2/pharmacology;
Fibronectins/metabolism;
Immunohistochemistry;
Neural Cell Adhesion Molecules/*genetics;
Rats;
Rats, Sprague-Dawley;
Real-Time Polymerase Chain Reaction;
Sialic Acids/metabolism;
Stem Cells;
Thyroid Hormones/*metabolism;
Triiodothyronine/pharmacology
- From:Yonsei Medical Journal
2013;54(1):246-252
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: Cell transplantation of myelin-producing exogenous cells is being extensively explored as a means of remyelinating axons in X-linked adrenoleukodystrophy. We determined whether 3,3',5-Triiodo-L-thyronine (T3) overexpresses the ABCD2 gene in the polysialylated (PSA) form of neural cell adhesion molecule (NCAM)-positive cells and promotes cell proliferation and favors oligodendrocyte lineage differentiation. MATERIALS AND METHODS: PSA-NCAM+ cells from newborn Sprague-Dawley rats were grown for five days on uncoated dishes in defined medium with or without supplementation of basic fibroblast growth factor (bFGF) and/or T3. Then, PSA-NCAM+ spheres were prepared in single cells and transferred to polyornithine/fibronectin-coated glass coverslips for five days to determine the fate of the cells according to the supplementation of these molecules. T3 responsiveness of ABCD2 was analyzed using real-time quantitative polymerase chain reaction, the growth and fate of cells were determined using 5-bromo-2-deoxyuridine incorporation and immunocytochemistry, respectively. RESULTS: Results demonstrated that T3 induces overexpression of the ABCD2 gene in PSA-NCAM+ cells, and can enhance PSA-NCAM+ cell growth in the presence of bFGF, favoring an oligodendrocyte fate. CONCLUSION: These results may provide new insights into investigation of PSA-NCAM+ cells for therapeutic application to X-linked adrenoleukodystrophy.
