Mesenchymal Stem Cells and Psoriasis

Pioneering attempt at stem cell therapy for psoriasis

Psoriasis is a well-known skin disease. Once onset, red papules or plaques may appear on the skin, covered with multiple layers of silvery white scales. It often occurs on the limbs, head and back, and even affects the whole body. Some cases are almost lifelong. not healed. There is currently no specific therapy. The disease mainly occurs in young and middle-aged people, and has a great impact on the physical health and mental status of patients. Epidemiological surveys show that there are currently about 6.5 million psoriasis patients in my country, with an incidence rate of 0.47%.

In 2006, Nanfang Hospital of Southern Medical University reported a case of chronic myelogenous leukemia complicated with refractory psoriasis cured by allogeneic mesenchymal stem cells; in 2002, two cases of allogeneic mesenchymal stem cell transplantation were reported in the Hematology Department of Beijing Military Region General Hospital A patient with acute leukemia and psoriasis was cured; more were reported in a total of 11 cases. After allogeneic or autologous stem cell transplantation, leukemia (or other hematological malignancies) and psoriasis have been well controlled or long-term complete remission, suggesting that mesenchymal stem cell therapy may become an effective treatment for psoriasis. As shown below

Immunomodulatory effect of mesenchymal stem cells

Mesenchymal stem cells are a group of stem cells that are mainly derived from mesoderm and have self-replication and multiple differentiation potentials. With the progress of research, it is found that mesenchymal stem cells also have immune regulation function. At present, the clinical research of mesenchymal stem cells is mainly used in anti-inflammatory treatment, tissue regeneration, graft-versus-host reaction, autoimmune diseases and gene transfection, such as anti-graft host disease, osteoarthritis, Crohn's disease, etc. disease, multiple sclerosis, etc.

There are more and more studies on the immunomodulatory effect of mesenchymal stem cells. Mesenchymal stem cells have a strong immunosuppressive effect on both adaptive immunity and innate immunity.

To put it simply: the suppression of adaptive immunity is mainly manifested in the immunosuppression of T lymphocytes and B lymphocytes, and the suppression of innate immunity is mainly manifested in the suppression of monocytes/macrophages, dendritic cells, Immunosuppressive effects of natural killer cells.

Specifically: the immunomodulatory effect of mesenchymal stem cells, including the inhibitory effect on the proliferation of CD8+ and CD4+ T lymphocytes and natural killer (NK) cells, by inhibiting the production of immunoglobulins by plasma cells, on mature dendritic cells ( DC) and inhibit the proliferation of regulatory T cells. These are the joint effects of PGE-2, HLA-G5, HGF, iNOS, IDO, TGF-β, IL-10, and LIF. At the same time, chemokines such as CXCL12 play a strong chemotaxis effect on lymphocytes and bone marrow mesenchymal stem cells during the process.

mesenchymal stem cell activity factor

I learned about this while working and researching at the Mayo Clinic, the number one medical institution in the United States. Active factors of mesenchymal stem cells (about "active factors", Mr. Bubu will do a special science popularization) are cytokines obtained from adult mesenchymal stem cells from various sources through in vitro expansion, or secreted extracellularly , or obtained by crushing cells. These active factors play an important regulatory role in the immune system and inflammation.

We analyzed the properties of these proteins by mass spectrometry (MALDI-TOF/TOF). Including prostaglandin E2 (PGE2), human leukocyte antigen G5 (HLA-G5), hepatocyte growth factor (HGF), inducible nitric oxide synthase (iNOS), indoleamine 2,3-dioxygenase (IDO ), transforming growth factor-β (TGF-β), leukocyte inhibitory factor (LIF), interleukin-4 (IL4), interleukin-6 (IL6), interleukin-8 (IL8), chemokine (CXCL12) and other active factors .

Among them, leukocyte interleukin is a class of cytokines that can promote the development and differentiation of T lymphocytes, B lymphocytes and hematopoietic cells. MMP2 is involved in the breakdown of extracellular matrix during embryonic development, reproduction and tissue remodeling. TGFB is a multifunctional protein that controls cell proliferation, differentiation, and other functions. VEGFA can promote angiogenesis and endothelial cell growth. CXCL12 exerts a strong chemotactic effect on lymphocytes and bone marrow mesenchymal stem cells during angiogenesis.

These active factors secreted by mesenchymal stem cells are the key components that we can currently use in the clinical treatment of skin immune inflammation-related diseases. These factors exert unique clinical effects in the treatment of psoriasis.

Psoriasis case

Clinically, psoriasis has four different conditions: (1) psoriasis vulgaris (2) pustular psoriasis (3) erythrodermic psoriasis (4) arthropathic psoriasis. More than 99% are psoriasis vulgaris.

Based on the research on the active factors and exosomes of mesenchymal stem cells, we realized that the active factors and various active ingredients secreted by these stem cells can rebuild the immune microenvironment of the skin, and at the same time have the functions of inhibiting inflammation, regulating immunity, and maintaining the local microenvironment of skin damage steady state effect. The most important thing is to activate and recruit autologous stem cells for immune regulation and repair. Therefore, we began to try to study the treatment of psoriasis vulgaris. Here we report a case of successful treatment of scalp psoriasis vulgaris with active factors of mesenchymal stem cells. It was implemented in early 2016 and has not yet recurred.

Conclusion

We believe that psoriasis vulgaris will be tackled in the near future with the help of multidisciplinary cooperation and immunomodulatory treatment with the help of cytokines. I also hope that we doctors and scientific researchers will do a better job for patients and alleviate their pain. Finally, with Mayo Clinic's motto " The needs of the patientcome first ", we hope to use our knowledge and new technologies to help all patients with psoriasis.

The charm of MSC is that she can always give us some surprises, and what we have to do is to study the mystery behind these surprises.