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Immunosuppressive effect of bone marrow-derived mesenchymal stem cells in inflammatory microenvironment favours the growth of B16 melanoma cells.

Han Z, Tian Z, Lv G, Zhang L, Jiang G, Sun K, Wang C, Bu X, Li R, Shi Y, Wu M, Wei L - J. Cell. Mol. Med. (2011)

Bottom Line: We first compared the promotive capacity of bone marrow-derived MSCs on B16 melanoma cells growth in vivo, pre-incubated or not with the inflammatory cytokines interferon (IFN)-γ and tumour necrosis factor (TNF)-α.We showed that the development of B16 melanoma cells is faster when co-injected with MSCs pre-incubated with IFN-γ and TNF-α compared with control groups.The impulsive effect of MSCs treated with inflammatory cytokines on B16 melanoma cells in vivo can be reversed by inhibitor or short interfering RNA of iNOS.

View Article: PubMed Central - PubMed

Affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medicial University, Shanghai, China.

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The rejection from Balb/c mice on B16 melanoma cells are reduced by the MSCs treated with proinflammatory cytokines. (A) Balb/c MSCs (1 × 106) were pretreated with inflammatory cytokines IFN-γ and TNF-α (20 ng/ml each) for 12 hrs and then mixed with B16 melanoma cells (5 × 106) to perform subcutaneous administration in the Balb/c mice armpit area. Tumour incidence was observed to evaluate the immunosuppressive function of MSCs that assisted the B16 melanoma cells from escaping the immunological rejection of Balb/c mice. As negative controls, B16 cells or MSCs alone were injected in Balb/c mice. (B) C57BL/6 MSCs were pretreated with inflammatory cytokines IFN-γ and TNF-α (20 ng/ml each) for 12 hrs. Fresh C57BL/6 splenocytes were activated by ConA (5 μg/ml) for 72 hrs and IL-2 (20 ng/ml) was added for proliferation. MSCs were cocultured in a 96-well with splenocytes (1 × 105/well) plate at a 1:10 ratio and cell proliferation was assessed 72 hrs later by 3H-Tdr incorporation. (C) MSCs were mixed with splenocytes (1 × 105/well) at different ratios (1:500, 1:250, 1:50, 1:10), and the proliferation was assessed 72 hrs later (*P < 0.05).
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fig02: The rejection from Balb/c mice on B16 melanoma cells are reduced by the MSCs treated with proinflammatory cytokines. (A) Balb/c MSCs (1 × 106) were pretreated with inflammatory cytokines IFN-γ and TNF-α (20 ng/ml each) for 12 hrs and then mixed with B16 melanoma cells (5 × 106) to perform subcutaneous administration in the Balb/c mice armpit area. Tumour incidence was observed to evaluate the immunosuppressive function of MSCs that assisted the B16 melanoma cells from escaping the immunological rejection of Balb/c mice. As negative controls, B16 cells or MSCs alone were injected in Balb/c mice. (B) C57BL/6 MSCs were pretreated with inflammatory cytokines IFN-γ and TNF-α (20 ng/ml each) for 12 hrs. Fresh C57BL/6 splenocytes were activated by ConA (5 μg/ml) for 72 hrs and IL-2 (20 ng/ml) was added for proliferation. MSCs were cocultured in a 96-well with splenocytes (1 × 105/well) plate at a 1:10 ratio and cell proliferation was assessed 72 hrs later by 3H-Tdr incorporation. (C) MSCs were mixed with splenocytes (1 × 105/well) at different ratios (1:500, 1:250, 1:50, 1:10), and the proliferation was assessed 72 hrs later (*P < 0.05).

Mentions: We implanted B16 melanoma cells in Balb/c mice with MSCs, which were pre-incubated or not with the inflammatory cytokines, to test the immunosuppression properties of MSCs that favour the B16 melanoma cells escaping from the rejection of Balb/c mice. While B16 melanoma cells developed into tumours rapidly after implanted subcutaneously in C57BL/6 mice, they were fully rejected in Balb/c mice, indicating no tumour formation at all. Once we implanted B16 melanoma cells mixed with MSCs in Balb/c mice, the incidence of tumour increased. Moreover, the tumour incidence could increase higher if the MSCs were pretreated with proinflammatory cytokines before they were mixed with B16 cells (Fig. 2A). These results indicate that MSCs have the ability to assist the B16 cells escaping from immune surveillance and this capacity is induced by proinflammatory cytokines.


Immunosuppressive effect of bone marrow-derived mesenchymal stem cells in inflammatory microenvironment favours the growth of B16 melanoma cells.

Han Z, Tian Z, Lv G, Zhang L, Jiang G, Sun K, Wang C, Bu X, Li R, Shi Y, Wu M, Wei L - J. Cell. Mol. Med. (2011)

The rejection from Balb/c mice on B16 melanoma cells are reduced by the MSCs treated with proinflammatory cytokines. (A) Balb/c MSCs (1 × 106) were pretreated with inflammatory cytokines IFN-γ and TNF-α (20 ng/ml each) for 12 hrs and then mixed with B16 melanoma cells (5 × 106) to perform subcutaneous administration in the Balb/c mice armpit area. Tumour incidence was observed to evaluate the immunosuppressive function of MSCs that assisted the B16 melanoma cells from escaping the immunological rejection of Balb/c mice. As negative controls, B16 cells or MSCs alone were injected in Balb/c mice. (B) C57BL/6 MSCs were pretreated with inflammatory cytokines IFN-γ and TNF-α (20 ng/ml each) for 12 hrs. Fresh C57BL/6 splenocytes were activated by ConA (5 μg/ml) for 72 hrs and IL-2 (20 ng/ml) was added for proliferation. MSCs were cocultured in a 96-well with splenocytes (1 × 105/well) plate at a 1:10 ratio and cell proliferation was assessed 72 hrs later by 3H-Tdr incorporation. (C) MSCs were mixed with splenocytes (1 × 105/well) at different ratios (1:500, 1:250, 1:50, 1:10), and the proliferation was assessed 72 hrs later (*P < 0.05).
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Related In: Results  -  Collection

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fig02: The rejection from Balb/c mice on B16 melanoma cells are reduced by the MSCs treated with proinflammatory cytokines. (A) Balb/c MSCs (1 × 106) were pretreated with inflammatory cytokines IFN-γ and TNF-α (20 ng/ml each) for 12 hrs and then mixed with B16 melanoma cells (5 × 106) to perform subcutaneous administration in the Balb/c mice armpit area. Tumour incidence was observed to evaluate the immunosuppressive function of MSCs that assisted the B16 melanoma cells from escaping the immunological rejection of Balb/c mice. As negative controls, B16 cells or MSCs alone were injected in Balb/c mice. (B) C57BL/6 MSCs were pretreated with inflammatory cytokines IFN-γ and TNF-α (20 ng/ml each) for 12 hrs. Fresh C57BL/6 splenocytes were activated by ConA (5 μg/ml) for 72 hrs and IL-2 (20 ng/ml) was added for proliferation. MSCs were cocultured in a 96-well with splenocytes (1 × 105/well) plate at a 1:10 ratio and cell proliferation was assessed 72 hrs later by 3H-Tdr incorporation. (C) MSCs were mixed with splenocytes (1 × 105/well) at different ratios (1:500, 1:250, 1:50, 1:10), and the proliferation was assessed 72 hrs later (*P < 0.05).
Mentions: We implanted B16 melanoma cells in Balb/c mice with MSCs, which were pre-incubated or not with the inflammatory cytokines, to test the immunosuppression properties of MSCs that favour the B16 melanoma cells escaping from the rejection of Balb/c mice. While B16 melanoma cells developed into tumours rapidly after implanted subcutaneously in C57BL/6 mice, they were fully rejected in Balb/c mice, indicating no tumour formation at all. Once we implanted B16 melanoma cells mixed with MSCs in Balb/c mice, the incidence of tumour increased. Moreover, the tumour incidence could increase higher if the MSCs were pretreated with proinflammatory cytokines before they were mixed with B16 cells (Fig. 2A). These results indicate that MSCs have the ability to assist the B16 cells escaping from immune surveillance and this capacity is induced by proinflammatory cytokines.

Bottom Line: We first compared the promotive capacity of bone marrow-derived MSCs on B16 melanoma cells growth in vivo, pre-incubated or not with the inflammatory cytokines interferon (IFN)-γ and tumour necrosis factor (TNF)-α.We showed that the development of B16 melanoma cells is faster when co-injected with MSCs pre-incubated with IFN-γ and TNF-α compared with control groups.The impulsive effect of MSCs treated with inflammatory cytokines on B16 melanoma cells in vivo can be reversed by inhibitor or short interfering RNA of iNOS.

View Article: PubMed Central - PubMed

Affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medicial University, Shanghai, China.

Show MeSH
Related in: MedlinePlus