Investigation of the Myogenic Differentiation Potential of Adipose Tissue Derived Stem Cells using RNA-interference
El-Mustapha Haddouti (MSc Biology with Biomedical Sciences)
Duchene muscular dystrophy (DMD) is the most rapidly progressing muscle Disease. DMD is caused by mutations in the X chromosome-linked DMD gene, which encodes the sarcolemma-stabilizing protein-dystrophin, causes progressive and degenerative muscle weakness and atrophy.
DMD afflicts ~1 in every 3,500 boys, making this lethal muscle-wasting disease the most prevalent hereditary muscle disorder. Moreover between 600 and 800 neuromuscular diseases are related to amyotrophia, which has no cure until now and finally leads to death.
Adipose-tissue, which can be obtained in large quantities from healthy donors, represents an excellent reservoir for stem cells to be used in degenerative muscle diseases. Human mesenchymal stem cells (hMSCs) in particular are gaining much attention as therapeutic agents.
The myogenic differentiation potential of adipose tissue-derived stem cells (ATSCs) will be investigated using different approaches. In addition to standard induction methods, these cells will be fused with dystrophin-negative muscle cells. The reprogramming capacity of myoblasts to recover the expression of defect protein after fusion with ATSCs will be examined.
The relatively new method of RNA-interference (RNAi) will be used. The RNAi-based mechanism specifically mediated by small-interfering RNAs (siRNAs) can silence target genes at the chromatin level through gene expression downregulation. Specific siRNA will be cloned into a vector and transfected into ATSCs to silence candidate genes involved in negative regulation of myogenic differentiation.
This study may further elucidate the cellular mechanisms of myogenic differentiation and may contribute to basic research and understanding of muscle dystrophy.
In co-operation with Prof. Anton Wernig, University of Bonn, Bonn/Germany