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

Abstract

Crohn's disease (CD) is a chronic, recurring disease of the gastrointestinal tract of unclear etiology. One of the new approaches to CD therapy is the use of the possibilities of stem cells, in particular, mesenchymal stromal cells (MSCs). Currently, the use of MSC in clinical practice for the treatment of chronic inflammatory and autoimmune diseases is being studied in patients who receive concomitant therapy with other immunomodulatory medications. 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 anti-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 patients 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 pronounced 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.

Stem Cell Therapy in Inflammatory Bowel Disease: A Review of Achievements and Challenges

“…Blood immunoassays show that the levels of pro-inflammatory factors, such as INF-γ, TNF-α, and IL-12-β, are significantly decreased and more pronounced in the combined ASA group. 113 Table 3 summarizes the clinical studies of MSCs in treating IBD completed in recent years.…”

“… AZA >6 month Clinical remission (CDAI < 150) at 12 months. [ 113 ] Abbreviations : Allo, Allogeneic; ASCs, adipose mesenchymal stem cells; Auto, Autogenous; BM-MSCs, Bone marrow mesenchymal stem cells; CD, Crohn’s disease; CDAI, Crohn’s disease activity index; CDEIS, Crohn’s Disease Endoscopic Index of Severity; HBI, Harvey-Bradshaw index; HSCT, hematopoietic stem cell transplantation; IBD, Inflammatory bowel disease; IL-10, interleukin-10; IP, intraperitoneal injection; IV, intravenous injection; mPP, Massively Parallel Processing; MRI, Magnetic resonance imaging; MSCs, mesenchymal stem cells; MSCT, mesenchymal stem cells transplantation; PBSCT, Peripheral blood stem cell transplantation; PDA-001, Human placenta-derived cells; PFCD, perianal fistula Crohn’s disease; RFCD, rectovaginal fistula CD; SCs, stem cells; SVF, Stromal Vascular Fraction; UC, Ulcerative colitis; UCBSCs, Umbilical Cord Blood stem cells; CTX, Cyclophosphamide; ATG, antithymocyte globulin; F-ara-A, fludarabine; AZA, azathioprine; N/A, Not provided. …”

“…Blood immunoassays show that the levels of pro-inflammatory factors, such as INF-γ, TNF-α, and IL-12-β, are significantly decreased and more pronounced in the combined ASA group. 113…”