Psoriasis is a chronic autoimmune skin disease that is triggered by both genetic and environmental factors, It affects 2 – 3% of the global population and based on the intensity of the disease, various treatments like ointments, pills, light treatments or biologics are prescribed to control the disease. However, in some cases, ​“the treatments tend to lose their effectiveness once they are discontinued, leading to the return of the disease” Priti Roy, Professor, Jadavpur University, West Bengal, points out.

In patients suffering from psoriasis, the immune system goes into overdrive. Primarily, an interplay between the antigen presenting dendritic cells that are found in skin tissue and T‑cells, a type of white blood cell, leads to abnormal skin cell growth. The presence of antigens activates the T‑cells, which in turn triggers the production of large amounts of cytokines, cell signalling proteins that regulate the immune response and inflammation. Some key factors such as TNF – α, interleukin− ¹⁷⁄₂₂, and interferon− γ, act together to trigger the keratinocyte growth factor. This leads to the over growth of keratinocytes, the cells that make up the outermost layer of the skin, resulting in, thick, scaly plaques on the skin’s surface.

For the last sixteen years, Roy has developed several mathematical models to find a cure for psoriasis. In the current model, developed along with Xianbing Cao, Professor at Beijing Technology and Business University,

we wanted to examine how mature Mesenchymal stromal cells (MSCs) interact with the relevant cell populations through cytokine signalling pathways and aimed to capture the intricate dynamics of psoriasis progression and treatment.

MSCs are a type of adult stem cells that have the ability to regenerate and form different cell types. These are present in various tissues, including bone marrow and the umbilical cord. Recent studies have shown that MSCs therapy can suppress psoriatic inflammation and reduce the overgrowth of keratinocytes by secreting different cytokines that can inhibit the activity of T‑cells and dendritic cells.

Although various factors contribute to the psoriasis progression, researchers simplified the model by focusing on only the cell-to-cell interactions between T‑cells, dendritic cells, keratinocytes and additional population of MSCs. The goal was to observe the density of keratinocytes in the affected region. Biologic molecules such as TNF‑α inhibitors (e.g., Etanercept, Infliximab, Adalimumab) are helpful in reducing inflammation and overgrowth of keratinocytes. However, in severe cases of psoriasis, TNF‑α inhibitors also may not be enough to fully control the disease.

The mathematical model showed that starting with a high dose of TNF‑α inhibitors was necessary to control the initial flare-up of psoriasis. As the disease became more manageable, the dose was gradually reduced. If the disease remained severe after 80 days of treatment with TNF‑α inhibitors alone, MSC therapy was introduced.

The local MSC counts reduce significantly and often are not functioning in severe cases of psoriasis. To address this, administering healthy MSCs via external source is needed. ​“We combined MSC transplantation along with a TNF- α inhibitor, when treatment with a TNF‑α inhibitor alone fails to achieve the desired therapeutic outcomes”, Roy added.

Researchers used the optimal control theory, to determine the most effective dosing schedule for TNF‑α inhibitors and MSCs. It is a mathematical approach to design treatment strategies to individual patients that maximises therapeutic benefits while minimising side effects and costs. Roy further added, ​“This involves MSC replacement therapy with six pulsed infusions, each delivering a dose of 3 cells/​mm³, administered every 10 days, alongside optimal control through a TNF‑α inhibitor.” 

Through numerical analysis it was determined that the addition of MSCs helped in suppressing the growth of keratinocytes in the affected region within two months of starting the combined treatment approach. Furthermore, the concentration of local MSCs and other cell types were also restored to normal level.

“Although the models are robust and offer valuable insights, one key limitation is that they rely on hypothetical data,’ said Sandip Banerjee, Professor at IIT Roorkee, who was not involved in the study. He adds, their biological relevance may remain limited unless clinical data is used to inform the parameters. However, 

Roy believes that since parameter values were sourced from various published studies, the model can be validated with clinical data, making it viable for biological applications.