Carbohydrates on the stem cells surface control their differentiation

Scientists from the University of York, UK, have shown that changing the structure of sugar chains located on the surface of mesenchymal stem cells could help promote bone growth in the body. The discovery, published on February 14, 2018 in the Journal of Cell Science, can be an important stage in the development of methods for treating of osteoporosis, a disease characterized by fragile and weak bones.

Glycans (chains of sugars) are high-molecular carbohydrates consisting of one or many types of monosaccharide residues (glucose, fructose, etc., as well as their derivatives of desoxysugar, amino sugars, uronic acids) bound by glycosidic bonds. They are part of the basic structural components of the cell.

Glycans, bound together in a complex with proteins and lipids, and also among themselves, form a glicom, a kind of carbohydrate passport of the body, organ or cells. Glycans play a key role in the processes of molecular and cellular recognition, participate in cellular metabolism, are responsible for the utilization of aging cells in the body, etc. However, their structure is random, which creates certain difficulties in their study and understanding.

It is proved that terminal modifications of glycans limit the process of cell differentiation. For example, lactosamine is involved in the self-renewal of stem cells, preventing their differentiation.

Experts in bone formation and cell biologists, who studying glycans, combined their knowledge to find out whether these carbohydrates might have a role to play in forming bone. The researchers treated cells with kifunensine, a chemical compound that inhibits the enzyme in the Golgi apparatus, as a result of which the structure of the glycans produced by it is disrupted.

“The chemical, kifunensine, is well known to alter the structure of sugar chains. It has been examined for potential drug treatments before, but is yet to make any clinical trials. We wanted to see what it might do to bone-forming stem cells in laboratory testing.

“The complexity of these sugars means that they have never been tested in this way before, but we found that after a couple of days, interrupting the sugars’ normal function enabled them to enhance bone formation processes in stem cells.”

“The chemical, kifunensine, is well known to alter the structure of sugar chains. It has been examined for potential drug treatments before, but is yet to make any clinical trials. We wanted to see what it might do to bone-forming stem cells in laboratory testing”, – said Dr. Daniel Ungar.

“The complexity of these sugars means that they have never been tested in this way before, but we found that after a couple of days, interrupting the sugars’ normal function enabled them to enhance bone formation processes in stem cells.”

In this study, the relationship between glycans and bone growth was first discovered. This may be the first step in the research of possible methods of treating osteoporosis and combating its main manifestation – brittle bones.

Paul Genever, Professor from the University of York’s Department of Biology, said: “Currently the most commonly used drugs for treating osteoporosis aim to prevent further bone loss to halt progression of the disease, but we have no reliable candidates for actually restoring bone strength”.

“This is an exciting step forward into understanding the role of these sugars in its relationship to bone growth, but we still have some way to go in realising just how this mechanism works and what would happen to the cells when treated inside the body.”

The team are now working to investigate whether the chemical treatment can be targeted to stem cells involved with bone growth to ensure that it has no adverse reactions on other cells in the body.

They are also doing further testing to understand why inhibiting the sugar chains has an impact on the way stem cells stimulate bone formation.