Researchers demonstrate new gel transplant method to grow healthy muscle fibres in mice with muscular dystrophy
By using lab-grown human muscle cells inside a special gel, researchers at the Blizard Institute, Queen Mary University of London and UCL were able to create new muscle tissue that includes nerves and blood vessels within host mice. They did this by using a gel-like substance as a transplant delivery method, without the need to alter the muscles of the recipient though damaging procedures.
The researchers showed that the human muscle fibres connected to the nerves of the mice forming neuromuscular junctions which were supported by the growth of new blood vessels. They also observed that some human muscles cells populated the surrounding tissue housing muscle stem cells, which have the potential to develop into new muscle tissue, with no evidence of tumour formation.
The paper, published today in Cell Reports Medicine is the first study which has demonstrated that this procedure is safe and able to generate muscle tissues which include nerve connections and blood supply using a gel-based delivery method from human to mouse. The study was conducted by Dr Anna Kowala, former PhD student in Dr Yung-Yao Lin’s lab at the Blizard Institute, Queen Mary University of London, in collaboration with Professor Jennifer Morgan’s laboratory at UCL.
Surprisingly, the human muscle tissue was still detectable after six months despite the risk of the mice’s immune systems rejecting the human tissue, as would be expected in human-to-animal transplantation. What’s also surprising is that the human muscle tissue became larger after six months, suggesting that it was continuing to mature over the long-term.
Skeletal muscle is responsible for the generation of all voluntary movements, such as walking and lifting objects. Muscular dystrophies are a group of genetic diseases that cause progressive weakness and wasting of skeletal muscle. Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in childhood, resulting in loss of ambulation, poor quality of life and premature death.
Currently there is still no cure for any form of muscular dystrophies. A promising approach for treating muscular dystrophies is cell-based therapy. However, the major challenges in developing cell-based therapies for muscular dystrophies are getting sufficient muscle tissue cells to grow and work properly inside the body (engraftment) and the delivery methods. The researchers hope that the results of this study will pave the way for future clinical trials of gel-like material-mediated cell therapy.
An important aspect of this new procedure, using a gel-like substance to transplant the cells, is that it requires no harmful modulation of the host animal muscle. Usually, donor cells with the potential to develop into muscle tissue are transplanted into host animals through intramuscular cell injection. To increase engraftment efficiency, the host animal muscles are modulated prior to direct intramuscular injection of donor cells using a range of procedures (e.g. irradiation, cryoinjury and tissue-damaging chemicals), which significantly limit their clinical translation.
This new delivery procedure removes the need for this, improving animal welfare in line with the 3Rs framework (Refinement, Reduction, Replacement) for animal research.
This project was co-funded by the Barts Charity, Action Duchenne, Duchenne Parent Project, Newlife Charity, Royal Society, Queen Mary Impact Fund and the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs).
More information
Research paper: Engineered human myogenic cells in hydrogels generate innervated vascularized myofibers within dystrophic mouse muscle on long-term engraftment. Kowala, Anna et al. Cell Reports Medicine, Volume 0, Issue 0, 102019