Secretome of Mesenchymal Bone Marrow Stem Cells: Is It Immunosuppressive or Proinflammatory?

Mesenchymal stem cells (MSC) are characterized by tolerogenic potential and therefore, are used in the treatment of autoimmune diseases such as graft-versus-host disease (GVHD) reactions after allogeneic hematopoietic cell transplantation to improve the transplant functions, as well as for the therapy and prevention of cytokine storm in COVID-19 patients and some other conditions. However, MSC can exhibit proinflammatory activity, which causes risks for their clinical use. We studied the cytokine profile of bone marrow MSC culture and demonstrate intensive production of IL-6, IL-8, and chemokine MCP-1, which participate in the pathogenesis of cytokine storm and GVHD.

Combination of Muramylpeptides from Gram-Negative Bacteria Corrects Cyclophosphamide-Induced Disorders of Hematopoiesis and Spleen Cell Composition in Mice with B16 Melanoma.

We studied the effect of a combination of three muramylpeptides from gram-negative bacteria (Polymuramyl) on hematological parameters, morphology of the spleen, and serum cytokine level in mice with B16 melanoma treated with cyclophosphamide. Intraperitoneal administration of cyclophosphamide to tumor-bearing animals sharply reduced the number of leukocytes, especially neutrophils, in the blood and depleted the cellular composition of the spleen white pulp. Subsequent three daily intramuscular injections of Polymuramyl in doses of 70 and 860 ng/mouse for 3 days, as well as subcutaneous injection of the reference drug filgrastim (granulocytic CSF) in a dose of 12 μg/mouse partially corrected hematopoietic disorders and restored the cellular composition of the spleen.

Effect of Albumin on Tumor Cells In Vitro.

The study examined the effect of BSA on cultured cells of breast cancer, erythroleukemia, and ovarian carcinoma. BSA cytotoxic activity was examined with light microscopy and spectrophotometry in the concentration range of 6.25 to 50 mg/ml.

Effect of Cathepsine L1 on Transformation of Malignant Melanoma B16 Cells into Melanocytes.

We studied the effects of cathepsins produced by immunocompetent cells of intact mice, mice with B16 melanoma, mice with removed B16 melanoma, and mice with removed Ehrlich carcinoma on the growth of B16 melanoma. Incubation of B16 melanoma cells with cathepsins from immunocompetent cells of intact mice, mice with B16 melanoma, and mice with removed Ehrlich carcinoma did not affect tumor growth. Incubation of B16 melanoma cells with cathepsin from immunocompetent cells of mice with removed B16 melanoma was followed by complete loss of malignancy by these cells.

Comparative Analysis of Cytotoxic Activity of New Nitrosyl Iron-Sulfur Complexes in Human Tumor Cells In Vitro.

We studied cytotoxic activity of new tetranitrosyl NO-generating binuclear iron-sulfur [Fe-S] complexes containing different ligands in the molecule against tumor cells in vitro. Cytotoxic activity of the most active complex with cysteamine (CysAm) was compared with that of antitumor drug cisplatin. Caspase activation and morphological changes in cells were visualized by fluorescence microscopy.