Gene corrected FSHD-IPS cells, once step closer to cell therapy for Facioscapulohumeral muscular dystrophy

Bosnakovski, Darko (2012) Gene corrected FSHD-IPS cells, once step closer to cell therapy for Facioscapulohumeral muscular dystrophy. In: Personalised Medicine: Better Healthcare for the Future, 17 to 22 June, 2012, Larnaca, Cyprus.

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Human induced pluripotent stem (IPS) cells overcome several disadvantages of human
embryonic stem cells, including host specificity and ethical issues. These cells can be
generating from different cell types of each donor making them suitable tool for autologous
cell therapy and tissue engineering. Furthermore, iPS cells generated from patients with
genetical disorders capture the disease genotype in the cell. These cells are good model for
studying pathology of the diseases and testing different therapies. One approach is cell
therapy by using specific cell types from genetically corrected IPS cells
Facioscapulohumeral muscular dystrophy (FSHD), one of the most common inherited
myopathies, is caused by a contraction within a subtelomeric array of D4Z4 repeats 4q35.2. It
is characterized by uneven and progressive weakness and atrophy of facial, shoulder and
upper arm muscle.
To develop cell based study model for FSHD and relevant source for cell therapy we
generated IPS cells from FSHD myoblasts and myoblasts from healthy donors. To induce
myogenic differentiation FSHD-IPS cells were transduced with Myf5, one of the key myogenic
transcriptional factors. Under certain conditions Myf5 modified cells differentiated in
myoblasts and fused to form myotubes. DUX4 expression was detected in all stages of IPS
myogenic differentiation, pluripotent, mesenchymal and myogenic stage. By this, we
established relevant diseases model to study FSHD. However, to overcome the issues of
comparison of IPS clones from different donors and variations acquired prior reprogramming,
and in same time to generate adequate cells for tissue engendering, we genetically corrected
FSHD-IP cells by removing 4qA161 allele. We targeted FSHD-iPS cells with a linear targeting
vector bearing a single homology arm of 500 bp followed by the neo cassette and human
artificial telomeric repeats (T2AG3), using zinc finger nucleases. Expression analyses reveled
that corrected FSHD-IPS clones do not express DUX4.

Item Type: Conference or Workshop Item (Lecture)
Subjects: Medical and Health Sciences > Basic medicine
Divisions: Faculty of Medical Science
Depositing User: Darko Bosnakovski
Date Deposited: 01 Feb 2013 09:19
Last Modified: 01 Feb 2013 09:19

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