Stem cells are a promising weapon for combating certain degenerative conditions, such as cancers and organ failure. Both of the two types of stem cells, embryonic and adult, are able to regenerate new cells and tissue, but embryonic stem cells (obtained from an early-stage embryo) can also differentiate into specialized cell types. The discovery of a unique property of mesenchymal stem cells (MSCs) at the University of Toronto may lead to an alternate way to grow specialized cell tissue while avoiding ethical controversy.
Professor J.E. Davies and Dr. William Stanford from the Institute of Biomaterials and Biomedical Engineering at U of T, Dr. Armand Keating, Director of the Cell Therapy program at Princess Margaret Hospital, and their students Rahul Sarugaser and Lorraine Hanoun recently found that MSCs are able to stimulate bone and cartilage growth, speed up wound repair, and increase autoimmune function.
In an interview with the Vancouver Sun, Keating said, “Scientists had seen potential in MSCs but had been largely unable to establish definitively that they had the properties of stem cells. Methods for isolating them were also inefficient, as they had to be extracted from the bone marrow of human donors or, more recently, from fat removed in liposuction.”
In their study published in Public Library of Science, Davies and his team discovered that MSCs are specific cells with the unique ability to differentiate into a variety of body cell types. “In particular, MSCs are known for differentiating into cells required in the support tissues of the body such as bone and collagen,” explains Davies. However, “In bone marrow, about one in every 100,000 nucleated cells is a mesenchymal stem cell. These kinds of numbers make it very difficult to experiment with.” Due to these low numbers, the scientific community has been slow to accept evidence for the existence of MSCs.
Since 2002, Davies’ group hypothesized that MSCs could be localized in connective tissue. “In fact, from our previous studies, we have found that the richest source of MSCs is the human umbilical cord, which is essentially all connective tissue. What is more surprising is that this rich source is discarded as medical waste in the millions by families every year,” explains Dr. Davies. With the help of this abundant MSC source, Davies and his team have finally provided concrete evidence for human MSCs at the single-cell level.
In addition to determining the existence of MSCs, they provided evidence of the two factors that characterize stem cells: self-renewal and differentiation. “As an MSC gives rise to a progenitor cell, it loses some ability to differentiate,” says Davies. Thus, there exists a hierarchy for MSCs, each having distinct differentiating capacities.
An MSC at the top of the hierarchy can give rise to any one of the five different lineages (bone, cartilage, fat, muscle, and fibroblasts). As you go down the hierarchy, a MSC loses the ability to differentiate into one of these cell types and ultimately becomes completely specialized. This finding enabled researchers to isolate MSCs at different stages and use them for drug screening and other clinical treatments.
Canada boasts an impressive list of accomplishments in the field of stem cell biology. Work done by pioneers James Till and Ernest McCulloch of the Ontario Cancer Institute in Toronto sparked the field of stem cell research in the 1960s, and Canada continues to be ranked in the top six countries internationally for its ongoing leadership in stem cell research.
Stem cell research has branched out into many discrete and exciting fields over the past 50 years. Davies’ fellow investigator Dr. Stanford and his team work on trying to model human diseases with genetically altered mice. “Now we can model human diseases with a rich human sample of MSCs that have been shown to exist and act in a similar manner to pluripotent stem cells [which have the potential to develop into a wide range of cell types],” explains Stanford.
Unlike other types of stem cells (i.e. embryonic), MSCs from either adult bone marrow or the umbilical cord are not under the same ethical scrutiny. Adult bone marrow is voluntarily provided and umbilical cords are essentially medical waste thrown out by many families. “MSCs are ready to be used for clinical applications right away and don’t require much more research before being implemented into clinical medicine,” says Stanford.
Currently there are close to 60 MSC trials in progress worldwide, showing great potential for the realistic applications of these stem cells. In addition to their regenerative role, MSCs possess a unique property which enables them to go undetected by the hosts’ immune system. This avoids the issue of matching the patient’s cells with MSCs and allows for a wider range of uses.
“This new research has immediate implications in the field of cell-based therapy and personalized medicine, which is one of the exciting [applications] of these mesenchymal stem cells,” explains Stanford.
