Clin Pediatr Hematol Oncol.  2010 Apr;17(1):51-58.

Hypoxic Treated Bone Marrow Cells Enhanced Foxp3 and IL-10 Expression in a Murine Liver Injury Model

• Joo SY
• Jung SO
• Cho KA
• Woo SY
• Seoh JY
• Ryu KH

Abstract

PURPOSE
It has been reported that bone marrow (BM)-derived stem cells retain the capability of regenerating organs, as well as functioning as an immune modulator. We previously reported that liver function recovered with bone marrow cells (BMCs) transplantation in a liver failure mouse by CCl4 injection and after hypoxic conditioned BMCs transplantation, cell migration and engraftment had been improved. We investigated immune modulation after hypoxic conditioned BMCs transplantation.
METHODS
To induce the acute liver failure, C57BL/6 mice were injected intra-peritoneally once a day with CCl4 (10microliter/g) for two consecutive days, and were used as liver injury recipients. Donor BMCs were incubated under the desired level of O2 (0.1% and 20%) for 24 hours. We then injected the conditioned BMCs through the tail vein into the CCl4-injected mice. For further analyzing immunological changes after transferring BMCexposed to hypoxia to CCl4 treated mice, we separated spleen cells after BMCs transplantation and analyzed phenotype changes of Foxp3, IL-10, IL-4, IL-12 and IFN- of CD4+ T cells.
RESULTS
The proportion of CD4+CD25+Foxp3+ cells, IL-10 secreting cells increased in CCl4 damaged mice after the BMCs transfers after hypoxic treatment. Although the proportion of IL-4 expressing CD4+ cells increased under the hypoxic conditions, did not have statistical significance. The percentage IFN-gamma and IL-12 expressing CD4+ cells did not show statistical significance.
CONCLUSION
It is suggested that hypoxic conditioned BMCs transplantation affected the immune modulation via inducing Foxp3+ and IL-10 secreting CD4+ cells in CCl4 damaged mice.

Keyword

Carbon tetrachloride; Bone marrow cells; Hypoxia; Regulatory T cell; Foxp3; IL-10; CD4+CD25+ cells

MeSH Terms

Animals
Anoxia
Bone Marrow
Bone Marrow Cells
Carbon Tetrachloride
Cell Transplantation
Humans
Interleukin-10
Interleukin-12
Interleukin-4
Liver
Liver Failure
Liver Failure, Acute
Mice
Phenotype
Spleen
Stem Cells
T-Lymphocytes
Tissue Donors
Transplants
Veins
Carbon Tetrachloride
Interleukin-10
Interleukin-12
Interleukin-4