Novel protein therapies that modulate biological processes, including those that improve healing of brain and spinal cord injuries, are promising treatment strategies. However, two obstacles must be overcome for the effective use of these treatments: maintaining protein bioactivity and controlled release of the proteins. The lab of Dr. Molly Shoichet has recently developed an affinity-based protein delivery system that overcomes these obstacles.

This new technique involves the preparation of a chemically modified hyaluronan and methylcellulose (HAMC) hydrogel that can bind any therapeutic protein of choice and be injected, for example, to a site of injury in the body. The system takes advantage of Src homology 3 (SH3) protein domains, which bind proline-rich peptides. The therapeutic protein, recombinant human basic fibroblast growth factor (rhFGF2), which promotes healing in rat models of spinal cord injury, was expressed as an SH3 fusion protein. The resulting rhFGF2-SH3 protein was then incorporated into the hydrogel that was covalently modified with a proline-rich peptide.

Using in vitro assays, the researchers found that the release of bioactive rhFGF2-SH3 from the HAMC hydrogel could be extended up to ten days when the gel was modified with a peptide exhibiting a strong affinity for SH3 domains. By varying the affinity of the peptide to the SH3 domain, the release of the protein drug could be finely tuned to accommodate different treatment requirements while maintaining high levels of rhFGF2 bioactivity. This technique will enable the development of protein therapies that require longer and localized delivery, including new regenerative therapies for brain and spinal cord injuries.

Tunable growth factor delivery from injectable hydrogels for tissue engineering. Vulic K, Shoichet MS. J Am Chem Soc. 2011 Dec 28. [Abstract]

Findings published by Dr. John Dick were included on a list released by the Canadian Cancer Society of the top 10 cancer research breakthroughs of 2011. Dr. Dick's team was recognized for their discovery of a hematopoietic stem cell that is capable of repopulating the entire blood system. These findings, published in Science, may relieve the demand for bone marrow for use in transplants, facilitating treatment of leukemia and other blood-related diseases. Learn more about the discovery by accessing the scientific article or read a summary in the July 2011 issue of the McEwen Monthly.

The first Ontario cardiac stem cell transplant was carried out in January 2012 as part of the Phase II IMPACT-CABG clinical trial. Close to 3 million stem cells were injected into a patient intraoperatively (following coronary artery bypass graft surgery) at the Peter Munk Cardiac Centre using UHN's specialized Organ Regeneration Laboratory. The study results will be pooled with the Maisonneuve-Rosemont Hospital in Montreal, and will allow researchers to test the safety and efficacy of the procedure. To read more, click here.

Congratulations to Dr. Molly Shoichet, who received the Clemson Award from the Society for Biomaterials for her contributions to the literature on biomaterials science. By merging protein and polymer biochemistry with cancer biology and neurology, Dr. Shoichet creates novel tools with important implications for regenerative medicine and the development of therapeutics for patients suffering from cancer, spinal cord injuries and neurological disorders.

Kudos to McEwen investigators, Drs. Ren-Ke Li (PI), Richard Weisel and Thomas Waddell (Co-PIs) for their recent success in the latest round of CIHR Operating Grants.