Science of stem cells

Satellite cell on muscle fibreOur fundamental research aims to identify and manipulate the genes that regulate self-renewal, migratory ability, survival and in vivo differentiation of cells that could potentially be used to treat disease.

We are also evaluating how modifications in cultivation procedures affect stem cell behaviour. It is crucial to understand these effects if we are to develop safe, reproducible regenerative therapies in the future.

Our focus is on stem cells of the skeletal muscle and epithelia.

Skeletal muscle

We will use fundamental research on stem cells in skeletal muscle to inform pre-clinical work and clinical trials focused on Duchenne muscular dystrophy (DMD). DMD results from a mutation in the cytoskeletal protein dystrophin.

Human mesoangioblastsSome key areas of our work are:

1. Factors that control the fate choices of myogenic stem cells

Our studies cover genetic, epigenetic and environmental factors that influence self-renewal, differentiation and regenerative capacity. We consider satellite cells, mesoangioblasts and CD133+ cells in this context. CD133+ cells are human stem cells isolated from patients’ blood and skeletal muscle, then engineered to produce functional dystrophin.

2. Methods for extending the proliferative lifespan of myogenic stem cells without affecting differentiation potential

We are attempting to extend cell lifespan by: (a) modification of myogenic cells using inducible genes; (b) identification of new culture conditions and growth media.

Epithelia

Our epithelial research focuses on the behaviour of stem cells in skin, ocular, oral and thymic epithelia. These studies will inform pre-clinical work and clinical trials focused on severe damage to the epidermis, ocular surface or oral mucosa.

Some key areas of our work are:
1. Molecular phenotypes of epithelial stem cells and the genetic programs underlying their properties

We are studying human epidermal, limbal-corneal, conjunctival, oral, urothelial and thymic stem cells with a view to identifying molecular phenotypes and the systems governing cell fate. We are developing transcriptome maps for stratified epithelia, and will use these to discover whether trans-differentiation is possible.

2. Molecular characteristics of epidermal stem cells and the pathways responsible for self-renewal

We aim to uncover: (a) the signaling molecules involved in the reconstruction of the stem cell niche when donor cells are engrafted; (b) why epidermal appendages, such as hair follicles and sweat glands, do not regenerate in human cultured skin grafts.

3. Differentiation of corneal stem cells and plasticity of oral mucosal stem cells

We are investigating: (a) the molecular switch that gives rise to conjunctival stem cell derived goblet cells; (b) the plasticity of oral mucosal stem cells. We hope that oral mucosal stem cells may be able to regenerate the corneal epithelium in cases of complete corneal destruction.

Clinical applications

Fibrin substratum prepared from a surgical glue. From Ronfard et al., TRANSPLANTATION 2000Stem cells have great potential for treating disease. In fact, skin stem cells have already been used for over 25 years to grow skin grafts for patients with extensive burns. However, problems still exist with these skin grafts, and we have a lot to learn before other types of stem cells can be used routinely in medicine.

OptiStem aims to pave the way for new stem cell therapies through a combination of basic stem cell biology, pre-clinical work and clinical trials.

Our clinical work focuses on potential treatment strategies for:

• Duchenne muscular dystrophy
• Blindness caused by destruction of the entire ocular surface (surface of the eye)
• Severe burns and degenerative skin diseases
• Severe damage to oral mucosa (thin layers lining the mouth)

Information for patients

Due to the experimental nature of these studies we cannot at the moment offer treatments; opportunities to participate in clinical trials will become available on the website at appropriate times. This website provides scientific information about our clinical research. If you are looking for general information on stem cells and their potential use in treating disease, please visit the Frequently Asked Questions section of EuroStemCell.org.

Pre-clinical work

Our pre-clinical work bridges the gap between fundamental stem cell biology and clinical trials. This part of our work includes:

• Detailed analysis of the long-term fates and in vivo efficacies of transplanted or engrafted cells in animal model systems
• Investigation of approaches to increase angiogenesis in damaged tissue to ensure sufficient nutrient and oxygen supply to regenerating tissue (a pivotal factor in efficient cell therapy)
• In-depth immunological studies to determine whether the stem cells we use elicit any adverse immune response
• Further studies to modulate the immune response and/or induce tolerance
• Development of reliable micro-surgical techniques

These investigations will allow us to optimize our protocols while progressing to clinical trials.

Clinical trials

We will carry out a number of early-stage (Phase I/IIa) clinical trials:

• Duchenne muscular dystrophy: Transplantation of pediatric patients with mesoangioblasts from healthy donors
• Duchenne muscular dystrophy: Transplantation of patients with CD133+ cells (genetically corrected stem cells from their own bodies)
• Ocular, urethral or oral epithelial reconstruction: Treatment of patients with grafts prepared using stem cells extracted from biopsies taken from their own bodies

Clinical trials will begin in 2010. More information will be posted here as the trials progress.

Publications

OptiStem began work in March 2009. We will post details of publications arising from our research on this page.

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Progress reports

OptiStem began work on 1st March 2009. Our first two years have seen great progress in all aspects of our work, including the beginning of clinical trials, advances in basic science and preclinical studies, as well as an exciting training and outreach programme. To find out more about our progress so far, download our first two Annual Report Summaries below.

Download Year 1 Annual Report Summary (pdf; opens in a new window)

Download Year 2 Annual Report Summary (pdf; opens in a new window)