Abstract

Relevance: The use of stem cells (SC) in cartilage damage is a promising and necessary direction: mature chondrocytes have a reduced division potential, as a result of which the natural repair of cartilage tissue defects, in particular the ear and nasal wings, occurs through fibroplasia, not regeneration. Immunological and pathophysiological aspects of therapy with allogeneic SCs largely depend on the systemic and local effect of cytokines and other biologically active substances (BAS) both on the part of the recipient and on the SCs themselves. Aspects of these relationships are multifaceted and ambiguous, so they require careful study and analysis. Among the many BARs affecting chondrogenesis, such multifunctional agents as transforming growth factor TGF-β1 and interleukin-6 attract special attention. The activation of the TGF-β1 gene occurs in response to tissue damage, the functions of TGF-β1, in particular, are the stimulation of the proliferation and activity of fibroblasts, this cytokine also regulates the expression of genes encoding collagens. IL-6 has, for the most part, a pro-inflammatory effect: it stimulates the migration of monocytes, simultaneously suppressing the proliferation of fibroblasts, and enhances the functional activity of osteoclasts, which can lead to cartilage degradation. But a small amount of IL-6 acts as a chondroprotector, inhibiting the activity of destructive metalloproteinases.

Purpose: To study the peculiarities of the dynamics of cytokine changes during the systemic use of native and preconditioned MSCs.

Material and methods: 44 rabbits were under supervision, in which the content of TGF-β1 and IL-6 in the blood serum of rabbits of experimental and control groups was determined by enzyme immunoassay (ELISA). Experimental groups of animals were intravenously injected once with 5 million native or preconditioned allogeneic MSCs after modeling the injury.

Results and discussion: Systemic use of MSCs is accompanied by systemic changes in the cytokine profile, in particular, TGF-β1 and IL-6. It is possible that the anti-inflammatory effect of MSCs (both direct and indirect) is a crucial part of this effect. In our study, no statistically significant differences were found in the content of TGF-β1 and IL-6 in the blood serum of experimental animals when using native or preconditioned MSCs.

It was found that in animals after the introduction of MSCs, a lower level of TGF-β1 and IL-6 was determined 3 months after the start of observation. Similar changes were observed when using both native and preconditioned stem cells.

Conclusions: Systemic use of MSCs is accompanied by changes in the cytokine profile, in particular, TGF-β1 and IL-6. In our study, no significant differences were found in the content of TGF-β1 and IL-6 in the blood serum of experimental animals when using native and preconditioned allogeneic MSCs.

Key words: Mesenchymal stem cells, regeneration, cartilage, preconditioning, cytokines.