university of toronto

Old cells need not apply: how a stem cell’s age can impact potential treatments

/ Yimy Villa / 2 Comments

Getting older is a normal, at times existential, part of life. The outward changes are abundant and noticeable: thinning of the hair, greying of the hair, and added lines to the face. There are also changes that happen that are not so abundantly clear in terms of outward appearance: slowing of healing time for bone fractures and a gradual loss of bodily function. The process of aging poses one very fundamental question — Could understanding how stem cells age lead to a greater understanding of how diseases develop? More importantly, could it guide the approach towards developing potential treatments? Two different studies highlight the importance of evaluating and understanding the process of aging in stem cells.

The first study, led by Dr. Michael Fehlings, looked at the impact of donor age in relation to stem cell therapies for spinal cord injuries (SCI). Dr. Fehlings, with a team of investigators from the University of Toronto and Krembil Research Institute, University Health Network, used an adult rat model to look at how cells derived from young vs. old stem cells affected tissue regeneration and recovery after a spinal cord injury.

Some rats with a SCI received cells derived from stem cells in the umbilical cord blood, which are considered “young” stem cells. The other rats with a SCI received cells derived from stem cells in the bone marrow, which are considered “old” stem cells. The results showed, ten weeks after treatment, that rats given the “young” stem cells exhibited a better recovery in comparison to those given the “old” stem cells.

In a press release, Dr. Fehlings stated that,

“Together, this minimally invasive and effective approach to cell therapy has significant implications on the treatment of traumatic cervical SCI and other central nervous system injuries. These results can help to optimize cell treatment strategies for eventual use in humans.”

The full results to this study were published in Stem Cells Translational Medicine.

The second, separate study, conducted by Dr. Stephen Crocker at UConn Health, looks at brain stem cells in people with multiple sclerosis (MS), a neurodegenerative disease caused by the inflammation and destruction of the insulation around the nerves, also known as myelin. Problems with insulation around the nerves can prevent or complicate the electrical signals sent from the brain to the body, which can lead to problems with walking or other bodily movements.

Drawing of a healthy nerve cell with insulation (left) and one damaged by multiple sclerosis (right). Image courtesy of Shutterstock

Dr. Crocker and his team found that brain stem cells in patients with MS look much older when compared to the brain stem cells of a healthy person around the same age. Not only did these brain stem cells look older, but they also acted much older in comparison to their healthy counterparts. It was also discovered that the brain stem cells of MS patients were producing a protein that prevented the development of insulation around the nerves. What is more remarkable is that Dr. Crocker and his team demonstrated that when this protein is blocked, the insulation around the nerves develops normally again.

In a press release, Dr. Valentina Fossati, a neurologist at the New York Stem Cell Foundation who evaluated these brain stem cells, stated that,

“We are excited that the study of human stem cells in a dish led to the discovery of a new disease mechanism that could be targeted in much-needed therapeutics for progressive MS patients.”

The complete study was published in the Proceedings of the National Academy of Sciences (PNAS).

Researchers Identify Potential New Cell Source for Spinal Cord Injury Treatments

/ Todd Dubnicoff / 1 Comment

Now that Asterias Biotherapeutics’ CIRM-funded, stem cell-based clinical trial for spinal cord injury (SCI) has safely treated its first group of patients and begun recruiting the second, should other SCI researchers close up shop? Of course not. Since it’s a first-in-human trial, there certainly will be room for improvement even if the therapy proves successful. And it may not work for every SCI victim. So the development of other therapeutic approaches is critical to ensure effective treatments for all patients with this unmet medical need.

spinalcordinjury_bbcgraphic

Graphic of spinal cord injury site
(BBC via JACOPIN/BSIP/SCIENCE PHOTO LIBRARY)

Enter the lab of Michael Fehlings at the University of Toronto. Their recent Stem Cells Translational Medicine study describes a potential, minimally invasive therapeutic strategy which involves a type of brain cell not previously studied in the context of SCI.

In the case of the Asterias trial, embryonic stem cell-derived cells called oligodendrocytes are being transplanted directly into the injured spinal cord to help restore the disrupted nerve signals that cause a whole range of debilitating symptoms, including painful tingling and loss of movement in arms and legs, loss of bladder control and difficulty breathing.

Instead of trying to directly repair the disconnected nerve signals, Fehlings’ team looked at reducing the damaging effects of inflammation that occur at the site of injury in the days and weeks following the spinal cord trauma. This sounds like a perfect job for mesenchymal stem cells (MSCs) whose anti-inflammatory effects are well established. But previous animal studies using MSCs for spinal cord injury have had mixed results. Different sources of MSCs are known to have different anti-inflammatory actions so perhaps this is the culprit behind the variability. On top of that, the exact mechanism of action isn’t well understood which presents a barrier to getting FDA approval for clinical trials.

So the current study performed a careful comparative analysis of the healing effects of human cord blood MSCs and human brain vascular pericytes (HBVPs) – MSC-like cells found near blood vessels in the brain – in a rat model of spinal cord injury. Shortly after the SCI injury, the cells were delivered into the rats through the blood. The blood levels of various cytokines – proteins that modulate the inflammation response – were measured for several days. The only cytokine that increased in the days after the cell delivery of either cell type was IL-10 which is known for its anti-inflammatory effects.

Examining the spinal cord one to seven days after injury, the researchers found that both MSCs and HBVPs were better than controls at reducing hemorrhaging, with the HBVPs showing better improvement. In terms of long-term effects on functional behaviors, the researchers showed that after three weeks, grip strength, body coordination, and hind limb movement were most improved in the HBVPs.

In a university press release, Fehlings described these promising results:

fehlings

Michael Fehlings

“Our study demonstrates that these cells not only display a MSC phenotype in a dish, but also have similar immunomodulatory effects in animals after spinal cord injury that are more potent than those of non-central nervous system tissue-derived cells. Therefore, these cells are of interest for therapeutic use in acute spinal cord injury.”

A lot more work will be needed to translate these findings into clinical trials but for the sake of those suffering from spinal cord injury it’s encouraging that alternative approaches to treating this devastating, life-changing condition are in development.