Effects of Sodium Copper Chlorophyllin on Mesenchymal Stem Cell Function in Aplastic Anemia Mice

Chin J Integr Med. 2013 May;19(5):360-6. doi: 10.1007/s11655-012-1210-z. Epub 2012 Sep 21.

Abstract

Objective: To investigate the effects of sodium copper chlorophyllin (SCC) on the proliferation, differentiation and immunomodulatory function of mesenchymal stem cells (MSCs) from mice with aplastic anemia.

Methods: A mouse model of aplastic anemia was established by exposure of BALB/c mice to sublethal doses of 5.0 Gy Co60 γ radiation, followed by transplantation of 2×10(6) lymph node cells from DBA/2 donor mice within 4 h after radiation. Aplastic anemic BALB/c mice were randomly divided into six groups: the treated groups, which received 25, 50, or 100 mg/kg/day SCC, respectively; a positive control group treated with cyclosporine A (CsA); and an untreated model control group (model group); while, the non-irradiated mice as the normal control group. SCC or CsA were administered by gastrogavage for 20 days, starting on day 4 after irradiation. Peripheral blood cells were counted and colony-forming fibroblasts (CFU-F) in the bone marrow were assayed. The ability of MSCs to form calcium nodes after culture in osteoinductive medium was also observed. The immunosuppressive effect of MSCs on T lymphocytes was analyzed by enzyme-linked immunosorbent assay and flow cytometry, to evaluate the efficacy of SCC in mice with aplastic anemia.

Results: Peripheral blood white cell and platelet counts were increased by medium and high SCC doses, compared with the untreated control. CFU-Fs were also increased compared with the untreated control, and the numbers of calcium nodes in MSCs in osteoinductive medium were elevated in response to SCC treatment. The percentage of Forkhead box protein 3 (FOXP3(+)) T cells was increased in T cell-MSC cocultures, and the cytokine transforming growth factor β1 was up-regulated in SCC-treated groups.

Conclusion: The results of this study suggest that SCC not only promotes the proliferation and differentiation of MSCs, but also improves their immunoregulatory capacity in mice with aplastic anemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia, Aplastic / blood
  • Anemia, Aplastic / pathology
  • Anemia, Aplastic / therapy*
  • Animals
  • Anthraquinones / metabolism
  • Biomarkers / metabolism
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / pathology
  • Calcium / metabolism
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Chlorophyllides / pharmacology*
  • Colony-Forming Units Assay
  • Female
  • Immunosuppression
  • Leukocyte Count
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred DBA
  • Osteoblasts / drug effects
  • Osteoblasts / pathology
  • Platelet Count
  • T-Lymphocytes / drug effects

Substances

  • Anthraquinones
  • Biomarkers
  • Chlorophyllides
  • alizarin
  • chlorophyllin
  • Calcium