Muscle fibres labelled green
About OptiStem
OptiStem brings stem cell biology and clinical science together in a drive to develop and test new stem-cell-based approaches to therapy. We are focussed on degenerative diseases of the skeletal muscle, and repair of diseased or damaged epithelial tissues such as the skin or cornea. In the first two years of the project we have made significant progress in all three strands of our work – basic science, pre-clinical research and our planned clinical trials.
Understanding cells and diseases
We would like to use tissue stem cells in new therapies, but we need a strong platform of basic knowledge to achieve this. How are stem cells in muscle and epithelia controlled? What makes them self-renew or differentiate into more specialised cells? How is that process regulated in the body so that muscles or other tissues grow and are repaired properly?
Satellite cell on muscle fibreWe have identified a number of gene networks and proteins involved in controlling the behaviour of satellite cells, the stem cells found in skeletal muscles. Many of these genes were not previously known to be involved in muscle growth. We have also made new discoveries regarding epithelial stem cells. For example, we found that epithelial stem cells from the thymus can be reprogrammed to behave like skin hair follicle stem cells [1].
As well as studying the cells we knew about, we have discovered a new type of stem or progenitor cells, called interstitial PW1+ cells, or PICS. PICS work with satellite cells to generate new muscle. The gene PW1 has also been found in stem cells in many other tissues and can be used to identify them as stem cells [2]. This finding may ultimately benefit the whole field of regenerative medicine.
Pre-clinical work
Pre-clinical work bridges the gap between fundamental stem cell biology and the clinic. As well as a good understanding of stem cells, we need to know how diseases develop and how the body responds.
Muscle fibres grown in vitro from mesoangioblastsWe have studied Duchenne muscular dystrophy in detail in the lab, and have investigated how the immune system responds to injections of mesoangioblasts – a type of vessel-associated stem cell that will be used in clinical trials with Duchenne patients. We have looked closely at what happens to transplanted cells and have found ways to improve the number of cells that reach the damaged muscle, survive and are able to function. Our studies have also established for the first time that mesoangioblasts have a measurable positive effect on the muscles in dogs with muscular dystrophy.
In our work on epithelia, we have developed an innovative microsurgical device that allows a single stem cell to be transplanted onto the surface of the eye. This is a major step forward in studies focused on understanding how epithelial stem cells can be used in future therapies. The technique allows us to study in detail what happens to an individual cell and to follow its daughter cells when it divides. This will enable us to understand more about how the cells work and what controls their behaviour after transplantation.
Clinical trials
OptiStem aims to carry out clinical trials focussed on Duchenne muscular dystrophy, and on reconstruction of epithelia after severe injury (the mucosa in the mouth, and the cornea of the eye). We have completed our first clinical trial for children affected by Duchenne muscular dystrophy. 
Eye of a patient after a chemical burn (left), repaired with a limbal stem cell graft (right)This trial was a very early study that did not involve treating the patients, but established the methods we need to measure how the disease progresses. The next step is a phase I/II clinical trial in which a six patients will be transplanted with mesoangioblasts from a healthy, HLA-identical brother or sister. This study will check the safety of the approach and will also check how effective the treatment is.
In a study on 112 patients[3], OptiStem scientists have also shown that epithelial stem cells grown in the laboratory can be used to restore sight after certain kinds of eye damage, such as severe corneal chemical burns. This study demonstrates the real potential of stem cell therapeutics in treating a common disorder. As a next step towards making this therapy more widely available, our partner at The Centre for Regenerative Medicine in Modena has recently established a GMP facility, an essential regulatory requirement for producing the cells needed to treat patients. Discussions are now underway with regulatory authorities about the next steps towards treating more patients.
All about stem cells in action
OptiStem and the public
We are keen to share and discuss our science with others, including the public, patients and regulators. As a partner in EuroStemCell, we are making a major contribution to development of eurostemcell.org as Europe’s stem cell hub. In 2010, we created the successful educational tool All about stem cells in partnership with EuroSyStem. Over the remainder of the project, we plan to develop an interactive tool explaining the process of clinical translation, and to hold a series of dialogue events with patients and regulators.
Further information
Useful background:
- The road to the clinic - a step-by-step guide to how basic science travels to the clinic
- EuroStemCell factsheets for more information on GMP or stem cells in the skin
More on OptiStem and its research:
- OptiStem Annual Reports for a more detailed scientific summary of OptiStem’s activities
- News story on research paper by Bonfanti et al about reprogramming thymic cells
- News story on research paper by Besson et al about identifying stem cells using the PW1 gene
- News story about clinical study on repairing the cornea
Image credits
Eye repair photograph Reproduced with permission from Massachusetts Medical Society and take from Rama et al, Limbal Stem-Cell Therapy and Long-Term Corneal Regeneration, N Engl J Med, 2010, 363:147-55, doi: 10.1056/NEJMoa0905955
Satellite cell on muscle fibre by Peter Zammit. Muscle fibres grown from mesoangioblasts by Giulio Cossu.
