Mesenchymal stromal cells of bone marrow and azathioprine in Crohn's disease therapy

Ter Arkh. 2018 Feb 15;90(2):47-52. doi: 10.26442/terarkh201890247-52.

Abstract

Aim: To evaluate the effectiveness of MSCs therapy in patients with CD receiving azathioprine (AZA).

Materials and methods: The study included 34 patients with inflammatory (luminal) form of CD. The 1st group of patients (n=15) received an- ti-inflammatory therapy using MSCs culture in combination with AZA. The 2nd group (n=19) received MSCs without AZA. The severity of the attack was assessed in points in accordance with the of Crohn's disease activity index (CDAI). Immunoglobulins (IgA, IgG, IgM), interleukins (IL) 1β, 4, 10, tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), transforming growth factor-1β (TGF-1β), C-reactive protein (CRP), platelets and erythrocyte sedimentation rate (ESR) at 2, 6 and 12 months from the beginning of MSCs therapy.

Results: The initial mean CDAI in the 1st group was 337.6±17.1 points, in the 2nd group - 332.7±11.0 points (p=0.3). In both groups of pa- tients there was a significant decrease in CDAI after 2 months. From the beginning of therapy MSCs: in the 1st group to 118.9±12.4 points, in the 2nd - 120.3±14.1 points (p=0.7), after 6 months - 110.3±11.1 and 114.3±11.8 points (p=0.8), respectively. After 12 months CDAI in the 1st group was 99.9±10.8 points, in the 2nd group it was 100.6±12.1 points (p=0.8). The level of IgA, IgG, IgM was significantly lower in the group of patients with a longer history of the disease and long-term ASA. After the introduction of MSC in both groups of patients with BC, there was a tendency for the growth of pro- and anti-inflammatory cytokines, with a significantly lower level of pro-inflammatory cytokines - INF-γ, TNF-α, IL-1β - in the 1st group, indicating potentiation of the immunosuppressive effect of MSCs and AZA, which provides a more pro- nounced anti-inflammatory effect.

Conclusion: Transplantation of MSCs promotes an increase in the serum of patients with CD initially reduced concentration of IG, cytokines and restoring their balance as the onset of clinical remission. The combination with AZA has a more pronounced anti-inflammatory effect.

Keywords: Crohn's disease; azathioprine; clinical remission; cytokines; immunoglobulins; luminal form; mesenchymal stromal cells.

MeSH terms

  • Azathioprine* / therapeutic use
  • Bone Marrow
  • Crohn Disease* / therapy
  • Humans
  • Immunosuppressive Agents* / therapeutic use
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells*
  • Tumor Necrosis Factor-alpha

Substances

  • Immunosuppressive Agents
  • Tumor Necrosis Factor-alpha
  • Azathioprine