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R&D
     
       
Our R&D projects includes:
 
In vitro cell-based technologies as alternatives  for animal testing

Drug and chemical screening

 

  Toxicity studies

 

  Biocompatibility of biomaterial
 
Cell therapy technologies for treating human diseases
    Therapeutic cancer vaccine technology platforms. We are actively seeking partners in the pharmaceutical industry and clinical centres in order to co-develop our patented gene-modified dendritic cell therapy for the treatment of human cancer.
    Muscle stem cell therapy for Muscular Dystrophy, FP7-HESUB
 
 
 
Muscle wasting diseases

There are approximately sixty different diseases and syndromes that present a skeletal muscle pathophysiology (for more information about diseases associated with skeletal muscle please visit the Muscular Dystrophy campaign website http://www.muscular-dystrophy.org/).

The majority of these disorders are associated with various forms of muscular dystrophy, with the pathology of the disease primarily relating to skeletal muscle. There are also diseases whose primary pathology are unrelated to skeletal muscle, but have secondary and tertiary downstream pathology in the musculoskeletal system.

The severity of skeletal muscle wasting pathology and the number of different muscle groups affected throughout the body is dependent on the associated disease. Probably the most dramatic example of skeletal muscle wasting is observed in Duchenne Muscular Dystrophy (DMD) patients, an X-linked congenital disease that affects approximately 1 in every 3000 live male births. Boys with this disease suffer from severe muscle wasting due to the absence of dystrophin, a membrane associated protein in the skeletal muscle that provides a structural stability to the individual myofibres.

With the structural integrity of the skeletal muscle compromised in DMD patients, the myofibres are more fragile and prone to damage more readily. Degenerating myofibres are repaired quite efficiently due to the presence of quiescent stem cells resident in the skeletal muscle known as satellite cells.Upon myofibre damage, satellite cells become activated and proliferate into myoblast precursors, which go on to differentiate into new myofibres or fuse with already existing myofibres to functionally compensate for the initial loss of the damaged muscle. In addition, the satellite cells repopulate their niche within the skeletal muscle, residing between the sarcolemma and basement membrane of myofibres. However, due to the fragility of the myofibres in DMD patients, the skeletal muscle is subjected to continuous rounds of degeneration and regeneration, which overwhelms and exhausts the regeneration capacity of the satellite cell niche.

The constant bombardment of degeneration/regeneration cycles within the skeletal muscle leads to the damaged myofibres being replaced by fibrotic extracellular matrix and adipose tissue, which in turn leads to the functional loss of skeletal muscle throughout the body. As a result, DMD patients usually require the use of a wheelchair by their early teenage years, due to functional muscle depletion in their arms and limbs.

In the following years, the heart and diaphragm muscles become severely affected by the disease, which leads to cardiac and respiratory complications that sadly results in the untimely death of the DMD patient.

 
 
 

Treatment strategies
To date there are no cures for DMD or any of the other known skeletal muscle related diseases. However, numerous gene and cellular therapeutic avenues are being explored, aimed at easing the suffering experienced by the patients and their family members who are unfortunate enough to be affected by any one of these debilitating diseases. In regards to DMD, gene therapeutic approaches are being adopted to restore the functional dystrophin gene product, which endeavours to reintroduce a functional protein to the myofibre membranes that will restore functional integrity back to the skeletal muscle.

Another approach is to restore the exhausted muscle stem cell niche within the damaged muscle via the transplantation of isolated and cultured cell populations. The obvious choice would be to transplant satellite cells, as these are the cells with the inherent myogenic capacity to regenerate skeletal muscle. Interestingly, increasing evidence suggests that non-myogenic cellular populations can also be used to repopulate skeletal muscle and the stem cell niche. Based on extensive research, clinical trials are being implemented to assess the efficacy of using such gene and cellular therapies to successfully correct the muscle wasting pathology apparent in musculoskeletal-related disorders.

For more information, please visit http://www.treat-nmd.eu/ for up-to-date information about the progression of clinical trials associated with neuromuscular diseases.

How can HESUB help?
Even though great advances are being made on a daily basis in research facilities around the world, many problems remain unresolved in regards to finding a suitable therapy for muscle wasting associated diseases. One such stumbling block is manufacturing satellite cells in suitable numbers for therapeutic transplantation, while maintaining their myogenic output.

Previous in vivo transplantation studies have shown that in comparison to freshly isolated satellite cells, satellite cells cultured in 2D, for only one or two passages following isolation, have a reduced capacity to create new myofibres. The reasons behind this transformation in 2D culture into a less efficient myogenic restoring satellite cell type are a mystery. HESUB’s goal is to update the current 2D technology used for culturing satellite cells by inventing a perfusable single use bioreactor culturing system inspired by the in vivo environment satellite cells reside within.

It is hoped that this novel environment will allow the propagation of large numbers of satellite cells that retain the highly efficient myofibre regeneration and muscle stem cell niche replenishment properties of satellite cells.

Our Mission
3H Biomedical will develop special process for large scale satellite cell production that is in line with international requirement. Our goal is to start the clinical trial in 2017.

       
 
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