Human mesenchymal stem cell (MSC) therapy that can be used to treat degenerative changes in the body and extracellular vesicles (EV) therapy used to deliver drugs, are promising treatments for discogenic low back pain (LBP). Discogenic LBP is characterized by the progressive loss of spinal discs, which act like cushions between the vertebrae and help you move, bend and twist. Although promising, major obstacles remain to be overcome. We see that the intervertebral discs from patients with LBP start to wear down and accumulate senescent cells. Normal cells may grow, may eventually release chemical messengers or perform actions and then die. Senescent cells stop growing and do not perform the activities they were meant to do. In this case, senescent cells will express and release messengers that contribute to an inflammatory environment that negatively affects resident disc cells and transplanted stem cells. Reducing senescence could therefore improve regenerative approaches.
Goal
Ortho-Vanillin (o-Vanillin) is a natural compound that we can find in essential oils of different plants. It has senolytic activity, meaning that it could remove these senescent cells, as well as anti-inflammatory properties and could be a valuable supplement to MSC and EV therapy for discogenic LBP. This study explored EV release and transfer between MSCs and intervertebral disc (IVD) cells and examined the effect on MSC differentiation and IVD cell phenotype in the presence and absence of o-Vanillin.
Methodology
Dr Haglund’s research team used direct co-culture models in this study. These types of models allow to grow cells in the laboratory and study how they communicate and interact between each other by releasing cellular messengers meant for certain types of cells. This allowed researchers to evaluate regeneration, inflammatory mediators, and senescent cells in cell pellets in the presence or absence of o-Vanillin. EV release (the action of releasing particles outside of the cell) and transfer between different types of cells (MSCs and IVD cells) were examined. The effects on MSC differentiation and IVD cell phenotype were also evaluated. In other words, researchers were interested to see the impact of o-Vanillin on young cells that needed to specialize and acquire mature cells characteristics to be able to perform the action they were meant to perform.
Main findings
This study demonstrates that o-Vanillin improved MSC differentiation towards an IVD-like cell, meaning that the MSC were able to develop into cartilage and connective tissue and perform the function they were meant to, such as protecting the space between the vertebrae. O-Vanillin also improved IVD cell phenotype. Co-cultures of MSCs and IVD cells resulted in increased matrix synthesis, fewer senescent cells and a decreased release of the cytokines IL6 and IL8. In other words, it improved the cellular environment and helped develop cells. The effects were further enhanced by o-Vanillin. o-Vanillin profoundly increased EV release and/or uptake by MSCs and IVD cells. IVD cell markers were significantly upregulated in both cell types in response to conditioned media of o-Vanillin-treated donor cells.
Take home message
In order for cells to develop and accomplish the role they are supposed to, in this case protect the space between our vertebras, we need to have a certain environment in place that will help them achieve their goal. This study demonstrates that a compound like o-Vanillin affects MSC and IVD cell communication and suggests that combining MSCs and senolytic compounds may be involved in the outcome of cell supplementation and EV therapy for LBP. When the environment is thus altered, there can be a development of a disease such as LBP and researchers work hard to prevent or treat the disease.
