In the case of osteoarthritis, preserving the cartilage through the local injection of stem cells is an option explored by researchers for several years. A team Inserm proposes using so-called “mesenchymal” stem cells, encapsulated in a microgel to increase their lifespan after administration and prevent them from migrating elsewhere. Ultimately, this approach could make it possible to offer patients a single therapeutic injection with a lasting effect.
Osteoarthritis is the most common joint disease. It is characterized by the destruction of the cartilage and damage to neighboring tissues (the subchondral bone and the membrane synovium): a painful and disabling phenomenon, associated with significant inflammation. While symptomatic treatments bring some relief to those affected, there is currently no way to preserve tissue once the process has begun. However, researchers have been studying for several years the possibility of using stem cells to protect cartilage. They are particularly interested in mesenchymal stem cells, which can easily be isolated from adipose tissue. Injected into the diseased joint, they do not take the place of the cells destroyed by osteoarthritis, but they produce growth factors which promote the survival of cells still in place. They also have an immunoregulatory effect, which reduces inflammation. Several studies have proven the value of this therapeutic approach in animals and humans, with a slowing down of tissue destruction and pain relief. But this work also underlines that it is still necessary to improve this technique in order to hope to obtain a significant and long-term benefit from it. The use of stem cells comes up against two major obstacles: the majority of stem cells die quickly after injection, and some migrate outside the joint. In mice, for example, less than 15% of the injected cells are still present after 10 days and none after 30 days.
A gel made from brown algae
At the University of Nantes, to remedy this problem without having to multiply painful, risky and expensive injections, the group of Catherine Le Visage, Inserm research director, proposes to encapsulate stem cells in a microgel. The idea is to confine them to the injection site while preserving their strengths. The researchers opted for a substance called “alginate”, a polymer extract of brown algae already used in medicine in dressings, and tested to encapsulate other types of cells, in particular pancreatic, to produce insulin and fight against diabetes. Inexpensive and biodegradable, it forms, in the presence of calcium, a gelled and permeable network which presents no known risk to health. The researchers used it to obtain particles of around 200 μm which each contain around twenty stem cells. Concretely, an alginate solution which contains stem cells is placed in wells of predefined shape and size, then the solution is gelled by adding calcium. Once the cells have thus been trapped in the gel, the microparticles are demoulded.
Conducted experiments in vitro et live in animals have shown that encapsulation does not hinder the survival of cells, nor the release of the therapeutic factors that they produce. Additionally, in a rabbit model with osteoarthritis, injection of a single dose of encapsulated mesenchymal stem cells reduced cartilage loss for at least 12 weeks. An encouraging first preclinical step. ” Further work, including with other animal models, will allow us to know how long the benefit persists and if the functional improvement is satisfactory. concludes Catherine Le Visage.
Catherine Le Visage dirige le groupe Heal (Hydrogels and joint translational research)within the Regenerative Medicine and Skeleton Unit (unit 1229 Inserm/Nantes University/Oniris), in Nantes.
Source : F. Nativel et coll. Micromolding-based encapsulation of mesenchymal stromal cells in alginate for intraarticular injection in osteoarthritis. Mater Today Bio, 13 February 2023; doi:10.1016/j.mtbio.2023.100581