NanoSTARS imaging for STEM cell therapy for arthritic joints

Regenerative medicine, particularly stem cell therapy, has shown great potential in the treatment of a wide range of illnesses, from diabetes to cancer, arthritis to transplant rejection. However, it is not yet clear how stem cells actually work inside the body.

This uncertainty makes it difficult for regulators to approve new stem cell therapies, and for doctors to prescribe them. Understanding the dynamics and distribution of stem cells is critical for optimising therapies for patients. STARSTEM is an exciting project which harnesses fundamental advances in the physics of imaging to validate stem cell treatments.

Key questions include:

  • Where do they go and how quickly do they get there?

  • How many stem cells actually engraft themselves in the area of interest?

  • How does healing occur over time.

Optoacoustic imaging (OAI)

An exciting new kind of imaging has emerged in recent years, Optoacoustic imaging (OAI), which can help us to understand what is happening within the body when therapeutic cells are administered. OAI uses laser light to build images of the tissue and other substances under the skin. When light is absorbed by tissue, some of that light is absorbed and converted to heat. This results in a pressure wave. Because different substances expand in different ways, and in response to different light wavelengths, a sophisticated image can be assembled. This means that OAI is uniquely capable of displaying functional markers of how and where stem cells do their work.

OAI takes advantage of the photothermal effect. When a tissue (or other substance) is illuminated with a bright light, such as a pulsed laser, some of that light is absorbed and converted to heat. The heat leads to an expansion of the illuminated material. This expansion creates a pressure wave in the local environment, which can be detected using ultrasound detectors. Because different substances expand in different ways, and in response to different light wavelengths, a sophisticated image can be assembled from the ultrasound readings caused by illumination with multiple laser wavelengths.

These functional markers include the level of oxygen in the blood, markers of inflammation, and the development of new blood vessels; these are all important indicators or hallmarks of the healing process.

OAI is inherently non-invasive – it can generate high-resolution optical imaging deep inside tissues in without harming the patient or study subject in any way (e.g. no need to puncture the skin). This means that the same subject can be imaged repeatedly and over time, enabling a complete picture of the regenerative healing process to emerge.

However, OAI relies on the use of laser light to illuminate the tissues to be imaged. Even the most effective light wavelengths have limited penetration depth beyond the skin. As a result, the effective imaging depth for OAI is typically a few millimetres. If OAI is to reach its full potential, it needs to generate good quality images at greater depth. STARSTEM will tackle this problem.

The STARSTEM Nanostar

The nanostar is a novel gold nano-particle, shaped like a star. Its unique makeup and shape means that it greatly enhances the photo-acoustic effect. It does this by concentrating the thermal response at the tips of the star’s arms. This generates a strong OAI signal. This effect is further enhanced by nanostars’ responsiveness to long-wavelength OAI lasers, which generates maximum thermal conversion and has deep penetration.

Nanostars act as a ‘contrast medium’ for OAI, greatly improving the image while having no impact on the therapy that is being monitored.

In STARSTEM, we will attach these nanostars to stem cells and extracellular vesicles. These tagged targets can then be detected in very small amounts and at a greater depth in order to track their distribution, engraftment, and subsequent activity.