Children with radial dysplasia are typically born without their thumb and radius (one of their forearm bones). Their forearm muscles, tendons and the surrounding connective tissue are abnormal, bending their wrist into a ‘U’ shape. Despite sophisticated surgical treatment to place their hand in a more normal position on their forearm, the wrist bowing often recurs as they grow, and their affected forearm is very short. The cause of this recurrence is unknown.
We have previously shown, in a model of radial dysplasia, the underlying soft tissue defect is within the muscle connective tissue layer. Normally, this organises and shapes the muscles and tendons as they develop; when this process is disrupted in our model, muscles are small and misshapen or absent, copying the changes found in radial dysplasia patients.
We think that the soft tissue defects in radial dysplasia patients stem from disruption of the normal organising role of muscle connective tissue on the developing muscles. We also believe that the nature of this disruption may affect the response of each individual patient to their treatment, and ultimately contribute to their long-term outcome.
Aims and Objectives
This project aims to understand how muscle connective tissue shapes limb soft-tissue development, and how this goes wrong in radial dysplasia. We plan to do this by comparing tissue samples donated with informed consent during reconstructive surgery by radial dysplasia patients with matched control samples from hand trauma patients.
- We will examine the tissue samples in our laboratory, looking for the changes we predict in tissue architecture and development, and measure how well-aligned or disrupted the tissues are by computer analysis.
- We will look for changed levels of key regulatory proteins identified in our model, using labelled antibodies to selectively identify them. These proteins are known to control the collagen ‘scaffolding’ around and within tissues.
- We will separate the cells into their different types, and grow them in the laboratory to show how they behave, both individually and when different cell types are combined.
- We will look for a self renewing ‘stem cell’ like population of muscle connective tissue cells.
- We will put our scientific findings in their clinical context by reviewing the outcomes at skeletal maturity in a group of patients who received current treatment. We will compare these outcomes with the muscle connective tissue changes, and also establish which outcomes matter most to patients.
Potential application and benefits
We expect our laboratory and clinical outcome data will be novel, and both data sets will help to explain each other. We hope this will lead to improved surgical design, potentially tailored to the individual soft tissue changes in each patient, and more precisely addressing the outcomes that patients’ value.
Our laboratory findings may also have wider application developing tissue engineered muscle, for use treating inherited defects, cancer or trauma.
RADIATE 