Mesenchymal Stem Cells: A New Step in the Treatment of Psoriasis

Psoriasis can presently be viewed as a very complex and chronic autoimmune disease that affects millions worldwide. Characterized by red, scaly patches on the skin, psoriasis can be a not only visible but often devastating disease regarding the quality of life and emotional well-being of a person. Traditional treatments, including topical creams, phototherapy, and immunosuppressive drugs, are effective for many but often have side effects and a limited duration of action. More recently, research has turned to a promising new approach for managing psoriasis.

Understanding Mesenchymal Stem Cells (MSCs)

Mesenchymal stem cells are a type of adult stem cell that possesses an extraordinary capability for differentiating into other kinds of cells such as bone, cartilage, muscle, or fat cells. MSCs are characteristically obtained from three sources of tissues: bone marrow, adipose, and umbilical cord tissue. Compared to other types of stem cells, MSCs possess some peculiar properties which could make them particularly suitable for therapeutic uses in autoimmune and inflammatory disorders:

Immunomodulation: The MSCs have the capacity to modulate the immune response of the

body by reducing inflammation through the inhibition of overly active immune cells.

Regenerative Properties: MSCs encourage repair of tissues that is of utmost importance in psoriasis because the skin cells grow and shed at a very fast and abnormal rate.

Anti-inflammation: MSCs produce factors which reduce chronic inflammation, characteristic of autoimmune diseases. Such attributes have made MSCs one of the favorite vehicles for the treatment of not only symptoms but perhaps some underlying mechanisms of psoriasis.

The Immune Link in Psoriasis

Psoriasis is a disease of an overactive immune response-in the context of the skin-inducing fast skin cell turnover as a result of inflammation. The immune cells of the body, such as T cells, begin to attack the healthy skin cells of the individual body, releasing cascades of inflammatory cytokines that include IL-17 and TNF-α. These inflammatory signals cause skin cells to start multiplying rapidly, which results in the typical red scaling patches seen in psoriasis.

While classic therapies have always based their action on the blockade of such inflammatory pathways, mesenchymal stem cells propose a holistic approach through their natural balancing of the immune system and reducing inflammation, hence offering a potential promotion of longer-lasting remission.

How do MSCs work in the treatment of psoriasis?

Studies involving the use of MSCs in the treatment of psoriasis have shown a variety of cardinal pathways through which these cells could help alleviate symptoms and probably modify the course of the disease. Following are some of the ways MSCs act within the body:

1. Modulating the Immune System

Among the most promising effects exerted by MSCs in psoriasis, one might point out the rebalancing of immune response. MSCs have been shown to shift the behavior of immune cells from pro-inflammatory Th17 cells to more regulatory T cells. This helps in restoring the balance of the immune system and reduces chronic inflammation driving psoriasis [(Jiao et al., 2022)]

2. Reducing Inflammatory Cytokines

MSCs produce anti-inflammatory proteins and cytokines, which neutralize the counterbalance caused by the overproduction of highly active inflammatory molecules like IL-17 and TNF-α in psoriatic skin. Scientists have noted that once MSCs are added to the environment of psoriasis, the amount of such cytokines drastically goes down, resulting in a reduction of inflammation in the skin and retardation of proliferation of the skin cells (Chen et al., 2019).

3. Skin Barrier Improvement and Regeneration

As skin rejuvenation is enhanced in tissue repair, MSCs further contribute to skin health. In psoriasis, this can cause an undermining of the skin barrier, leaving it more susceptible to dryness, itching, and infection. MSCs restore this barrier through promoting the production of collagen and other essential skin components, thereby strengthening the skin and reducing lesion severity.

4. Exosome Therapy

Moreover, the MSCs produce small vesicles known as exosomes, which carry proteins and signaling molecules that may be involved in modulating immune responses. Indeed, several studies have shown that exosomes derived from MSCs reduce the severity of psoriasis through the downregulation of inflammatory markers, adding a point of interest concerning therapy without the use of living cells per se.

Clinical Evidence: What the Research Says

Pre-clinical and early-phase clinical investigations conducted so far with MSCs as potential therapies in psoriasis are encouraging:

Mouse Model Studies: Involving MSCs in preclinical studies using mouse models of psoriasis, they have shown a great efficiency in reducing inflammation and skin thickness. It could be developed further that MSCs decrease not only the immune cell infiltration into the skin but also retard the production of inflammatory cytokines, thus preventing rapidly cycling skin cells.

Human Clinical Trials: Although these are still mostly in their infancy, human clinical trials of MSC treatment for psoriasis have seen encouraging results. For example, MSCs extracted from a small group of patients serving with severe psoriasis and administered injections of MSCs derived from the umbilical cord showed marked improvement in the condition of their skin and inflammation of it. In some cases, remission was sustained for many months following infusion, suggesting that this might be a long-acting therapy.

Case Reports and Anecdotal Evidence: Some case reports of the application of MSC therapy to psoriasis patients have shown that even patients suffering from obdurate, treatment-resistant psoriasis have responded quite well to infusions of MSCs, with a decrease in symptoms and minimal side effects.

Advantages of MSC Therapy in Psoriasis

Advantages of MSC therapy over the conventional treatments for psoriasis include the following:

1. Minimized Side Effects

MSCs are generally well tolerated and devoid of the significant side effects one could have when using long-term immunosuppressive drugs, which would always carry the risk of weakening the immune system and increasing the risk of infection.

2. Chance of Longer-term Remission

MSCs can have effects on the immune system that are long-lasting, which in some cases induces protracted remission. This stands in contrast to many of the conventional therapies, which, in order for their effect to be maintained, need to be ongoing.

3. Non-invasive sources of abundant supply

Because they can also be sourced from abundant tissues like the umbilical cord and fat tissue that are considered to be well-endowed and ethically available, MSCs could therefore become widely used.

4. Targeted Immune Modulation

MSCs do not act in an indiscriminate suppression of the immune system but would restore the balance in it. Since the action of such stem cells is targeted, there is minimal risk of losing total immunity, which is a big concern with conventional immunosuppressive therapies.

What does the future hold?

While the potential of MSCs in psoriasis is great, a lot remains to be done. Clinical trials should be done to understand exactly how MSCs should be optimized for psoriasis treatment, including sourcing, dosing, and methods of delivery for MSCs. The option of combining MSCs with available treatments like biologics for even better results is another field of study being researched.

One of the interesting strategies under keen investigation is the engineering of MSCs to enhance their therapeutic performance. For instance, it is possible to engineer the MSCs such that they overexpress certain proteins, such as hepatocyte growth factor, which has also been found to confer additional anti-inflammatory benefits in psoriasis.

Conclusion: A New Era in the Treatment of Psoriasis?

Mesenchymal stem cells are at the forefront of regenerative medicine, opening new pathways into the treatment of diseases like psoriasis. Though not yet standard therapy, MSCs have properties that will give a more holistic and effective approach toward the management of psoriasis, including immune modulation, anti-inflammation, and regeneration.

MSC therapy will bring greater relief to psoriasis patients and extend the time between treatments, considering reduced side effects. This is potentially going to revolutionize the treatment of people who have this chronic disease. Until research is continued, the hope is that a future in which MSCs are readily available to dermatology brings new hope and healing for individuals affected by psoriasis.

References

1. Ahn, H., Lee, S. Y., Jung, W., Pi, J., & Lee, K. (2021). Psoriasis treatment using minimally manipulated umbilical cord-derived mesenchymal stem cells: A case report. World Journal of Clinical Cases, 9 (23), 6798-6803.

2. Chen, M., Peng, J.-J., Xie, Q., Xiao, N., Su, X., Mei, H.-H.,. & Cheng, L. (2019). Mesenchymal stem cells improve moderate-to-severe psoriasis by reducing T1 interferon production from plasmacytoid dendritic cells. Stem Cells International, 2019.

3. Jiao, J., Zhao, X., Wang, Y., Liang, N., Li, J., Yang, X.,. & Zhang, K. (2022). Normal mesenchymal stem cells could improve the abnormal function of T cells in psoriasis by upregulating transforming growth factor‐β receptor. The Journal Of Dermatology, 49 (7), 988-997.

4. Meng, H., Wei, F., Zhou, Y., Hu, L., Ge, Z., Jin, J.,. & Wu, C.-T. (2021). Overexpression of hepatocyte growth factor in dental pulp stem cells ameliorates the severity of psoriasis by reducing inflammatory responses. Stem Cells and Development.

5. Sah, S. K., Park, K. H., Yun, C., Kang, K., & Kim, T.-Y. (2016). Effects of human mesenchymal stem cells transduced with superoxide dismutase on imiquimod-induced psoriasis-like skin inflammation in mice. Antioxidants & Redox Signaling, 24 (5), 233-248.

6. Zhang, Y., Yan, J., Li, Z.-G., & Sun, Q. (2020). Exosomes from human umbilical cord mesenchymal stem cells alleviate psoriasis-like skin inflammation.