Exploring Schwann cells
His time as a house officer at Queen Mary Hospital in Hong Kong left him with deep empathy for patients with spinal cord trauma. Witnessing their struggle to perform simple tasks like breathing and eating, and the complications they have to endure, such as recurring skin and bladder infections from being bed-bound, instilled in him a resolve to explore further the complexities of spinal injuries. He recalls that many of these patients were young and full of dreams, just like him. “I guess that got to me,” he says.
Shea’s current research explores the generation of Schwann cells (specialist cells crucial for tissue repair, axonal regrowth and remyelination following injury to peripheral nerves) from bone marrow stromal cells with a view to transplantation in spinal cord injury sites.
Early in vitro (petri dish) studies demonstrated that bone marrow stromal cells cultured with certain growth factors could differentiate into Schwann-like cells. Seeding these cells into a biocompatible tube (essentially a transport vehicle) and then transplanting them into a peripheral nerve injury site, like a sciatic nerve, stimulates nerve growth. While these are still early days due to the nature of animal studies, the results look promising. The rats have demonstrated improved recovery, increased normal gait patterns and better functionality.
A key challenge is to ensure that once the bone marrow stromal cells differentiate into Schwann cells they stay that way. Unfortunately, they tend to revert to their original bone marrow stromal cell state when the growth factors are removed. This has serious implications as they could potentially develop into tumours when transplanted. However, Shea and his colleagues found that when the growth factor-treated bone marrow stromal cells were cultured on the surface of neurons the differentiation into Schwann cells became permanent – or fate-committed as Shea describes it.
So what we are doing now is trying to do the same with human bone marrow stromal cells, to generate Schwann cells by identifying what exactly is on the surface of the neurons which is causing this fate-commitment, some mechanism. It’s answering a basic science question as well as helping us move onto the bedside.
The practical applications will take some time. Shea says he is hopeful that eventually it will be possible to generate fate-committed Schwann cells and seed them into grafts in spinal cord injury patients. After removing the scar tissue within the injury sites, the graft of Schwann cells would be transplanted to bridge the injury and stimulate new nerve growth. The aim is to promote better functional recovery and that translates into some measure of improved quality of life.
Dr Graham Shea began his medical studies in 2003 at the University of Hong Kong. In his fourth year of medical school in 2007, he took a break to complete a Master of Research in Medicine. He then continued his research studies for another three years and obtained his PhD in 2010 with the assistance of funding from the Croucher Foundation. Following this, he returned to medical school and completed his MBBS, qualifying as a medical doctor in 2012.
Funding from the Croucher Foundation in the form of a Clinical Assistant Professorship has ensured that Shea is able to continue his passion for research, whilst undergoing clinical rotations as a resident doctor at the Department of Orthopaedics and Traumatology at Queen Mary Hospital. His research is published in Experimental Neurology, Biomaterials, and CNS And Neurological Disorders – Drug Targets.