A study by McEwen Centre Director Dr. Gordon Keller has demonstrated a new method for generating chrondrocytes that are capable of forming articular cartilage in vitro and in vivo.

While other studies have described the successful differentiation of human pluripotent stem cells (hPSCs) into cells of the chondrocyte lineage, Dr. Keller's is the first to delineate the signalling molecules that direct the generation of articular chondrocytes in vitro.

The results, published in Nature Biotechnology, showed that activation of the TGFß signalling pathway promotes the development of the articular chondrocyte lineage. These hPSC-derived chondrocytes were able to generate and maintain a stable cartilage graft in vivo for up to 12 weeks.

"This is an exciting and encouraging first step in producing functional tissue for joint repair," says Dr. Keller. "Working with our partners at Mount Sinai Hospital, the Arthritis Program at Toronto Western Hospital and the University of Guelph, we are proceeding to transplant the stem cell-derived tissue into the joints of animal models to test its ability to repair damaged cartilage."

You can watch Dr. Keller discuss the possible implications of this work on a recent CTV News interview by clicking here.

This work was supported by Rob and Cheryl McEwen, the McEwen Centre for Regenerative Medicine, the Canadian Institutes of Health Research, the Krembil Foundation, Michael and Yetta Bregman in collaboration with the Campaign to Cure Arthritis, and the Toronto General & Western Hospital Foundation. G Keller holds a Tier I Canada Research Chair in Embryonic Stem Cell Biology. Image courtesy of Stock Up.

Generation of articular chondrocytes from human pluripotent stem cells. Craft AM, Rockel JS, Nartiss Y, Kandel RA, Alman BA, Keller GM. Nature Biotechnology. 2015 May 11. [Abstract]

PTC Therapeutics recently announced that it will begin a clinical trial at the Princess Margaret Cancer Centre to evaluate the safety of a drug known as PTC596, which specifically targets cancer stem cells.

Originally discovered in the early 1990s by McEwen Centre Researcher Dr. John Dick, cancer stem cells have now been found within a wide variety of tumours as well as in patients with blood cancers. These cells have the unique ability to form new cancer cells or produce cells with identical stem cell-like properties. Cancer stem cells are also capable of evading chemotherapy and radiotherapy treatments, and may largely be responsible for the failure of certain cancer therapies and/or cancer recurrence.

PTC596 inhibits the function and activity of a protein known as B cell moloney murine leukemia virus integration site 1 protein (BMI1), which is critical to the survival and growth of cancer stem cells.

This first-in-human trial is a critical initial step towards bringing this potentially life-saving treatment to the clinic as it will determine the safety and the effectiveness of PTC596 as a cancer therapy.

“Targeting cancer stem cells by BMI1 inhibition is a promising approach to address the challenge of drug-resistant cancers,” stated Princess Margaret Cancer Centre Senior Scientist Dr. Lillian Siu. “Cancer is a complex problem and the development of treatments that focus on molecular targets shows promise for the next generation of cancer therapies.”

A study by McEwen Centre Researcher Dr. Michael Fehlings, undertaken in collaboration with researchers in Calgary and Zurich, has found that neural stem cells can restore sensation in patients with spinal cord injury.

The international study, led by StemCells Inc., was conducted to evaluate the safety and preliminary efficacy of using human neural stem cells (hNSCs) to treat chronic spinal cord injury. During the trial hNSCs were injected directly into patients with spinal cord injuries, both above and below the site of injury. Patients were then monitored for a 12 month period following the treatment.

Out of the 12 patients who received hNSCs, seven had sustained improvements in sensory function, which occurred consistently approximately three months after transplantation and persisted until the end of the study. The study results also revealed that the hNSC treatments were safe and did not have any adverse effects.

Explains Dr. Fehlings, "The fact that a significant number of patients recovered some ability to feel sensation suggests that the stem cells partially repaired spinal cord damage. Based on these promising results, we have initiated a larger clinical trial that will determine whether these stem cell treatments can improve motor function in patients with cervical cord injuries, which occur higher up in the spine and typically cause greater damage."

Abstracts are currently being accepted for the 2015 Till & McCulloch Meetings—Canada’s leading forum for stem cell research.

This year’s event will be held in Toronto, Ontario and will feature presentations on all aspects of stem cell and regenerative medicine research, including stem cell therapies, immunotherapy and stem fate. For more details on this event visit the conference website.