Production of growth factors, pro – and anti-inflammatory cytokines by postnatal MMSCs from various tissue sources during in vitro co-cultivation with immunoisolated pancreatic β-cells

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Abstract

The article presents the results of evaluating growth factors, pro – and anti-inflammatory cytokine production by multipotent mesenchymal stem cell cultures under the conditions of co-cultivation with immuno-isolated beta-cells of the pancreas. β-cell transplantation is a minimally invasive therapeutic approach (compared to transplantation of entire pancreas), and it provides better metabolic control with respect to insulin administration. However, when transplanting β-cells, there is always a risk of immune rejection of the grafted cells. It is generally recognized that encapsulation is an effective means of immunological protection against the recipient’s immune system during transplantation. Regulation of the autoimmune response to transplanted cells is crucial for the treatment of type I diabetes mellitus. In recent years, along with replacement of islet cells, much attention has been paid to the use of multipotent mesenchymal stem cells with immunomodulatory and/or immunosuppressive properties, aimed for the correction of diabetes mellitus. Either in vitro and in vivo, they impact not only T-lymphocytes, but also B-lymphocytes, dendritic and NK-cells. Mesenchymal stem cells are able to inhibit proliferation of immune cells and reduce their secretion of inflammatory cytokines, acting as auxiliary cells to improve the survival of islets in the early post-transplant phase. Combined transplantation of multipotent mesenchymal stem cells and pancreatic β-cells is a promising approach to the treatment of type I diabetes mellitus. Deeper study of the mechanisms that cause their cytoprotective effect upon the transplant may be helpful for implementation of this therapeutic approach and improve its efficiency. In our study, a 1% solution of low-viscosity sodium alginate with addition of saline solution (0.9% sodium chloride) was used to create immuno-insulating scaffolds, and a 2.2% BaCl2 solution was added for polymerization. Decreased production of proinflammatory cytokines (TNFα, IL-12, IL-5) and growth factor (GM-CSF) was registered in co-cultures of β-cells with mesenchymal stem cells of bone marrow origin, and those obtained from subcutaneous adipose tissue. Anti-inflammatory activity was more pronounced in adipose stem cells and their immunomodulatory effects were shown via changes of their cytokine-producing activity. Hence, the multipotent mesenchymal stem cells obtained from adipose tissue and bone marrow have shown to exert cytoprotective effect upon pancreatic beta-cells by shifting the cytokine-producing activity towards an antiinflammatory profile.

About the authors

A. G. Goncharov

Immanuel Kant Baltic Federal University

Author for correspondence.
Email: agoncharov59@mail.ru
ORCID iD: 0000-0001-6967-8838

 PhD (Medicine), Senior Research Associate, Center for Immunology and Cell Biotechnologies

36010, Russian Federation, Kaliningrad, Pobedy ave., 189, apt 15 

 Phone: 7 (911) 865-20-66 

Russian Federation

V. V. Shupletsova

Immanuel Kant Baltic Federal University

Email: fake@neicon.ru

 PhD (Biology), Senior Research Associate, Center for Immunology and Cell Biotechnologies 

36010, Russian Federation, Kaliningrad, Pobedy ave., 189, apt 15 

Russian Federation

N. M. Todosenko

Immanuel Kant Baltic Federal University

Email: fake@neicon.ru

 PhD (Biology), Research Associate, Center for Immunology and Cell Biotechnologies 

36010, Russian Federation, Kaliningrad, Pobedy ave., 189, apt 15 

Russian Federation

E. A. Goncharova

Immanuel Kant Baltic Federal University

Email: fake@neicon.ru

 Student, Medical Institute 

36010, Russian Federation, Kaliningrad, Pobedy ave., 189, apt 15 

Russian Federation

L. S. Litvinova

Immanuel Kant Baltic Federal University

Email: fake@neicon.ru

 PhD, MD (Medicine), Head, Center for Immunology and Cell Biotechnologies, Professor 

 36010, Russian Federation, Kaliningrad, Pobedy ave., 189, apt 15 

Russian Federation

References

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Copyright (c) 2021 Goncharov A.G., Shupletsova V.V., Todosenko N.M., Goncharova E.A., Litvinova L.S.

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This work is licensed under a Creative Commons Attribution 4.0 International License.
Свидетельство о регистрации СМИ ПИ № 77 - 11525 от 04.01.2002 выдано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).


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