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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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MSCs treated with proinflammatory cytokines favour the growth of tumour. (A) MSCs at passage 8 were grown under different conditions that favour differentiation into either adipocytes (for 14 days), or osteoblasts (for 14 days), as described in ‘Materials and methods’. The presence of triglycerides, characteristic of adipocytes, was revealed by staining with oil red O. Calcium deposition, indicative of osteoblasts, was stained with Von Kossa stain. (B) MSCs derived from C57BL/6 mice were stained with commercially available antibodies to analysis the surface marker by flow cytometry (red). Corresponding antibodies of the same isotype were used as controls (white). (C) C57BL/6 MSCs (1 × 106) were pretreated with proinflammatory 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 C57BL/6 mice armpit area. After 14 days of implantation, the animals were sacrificed and tumours were dissected. The weight and volume of B16 tumours were measured. The weight of tumour were measured after been removed from the mice. (*P < 0.05).
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fig01: MSCs treated with proinflammatory cytokines favour the growth of tumour. (A) MSCs at passage 8 were grown under different conditions that favour differentiation into either adipocytes (for 14 days), or osteoblasts (for 14 days), as described in ‘Materials and methods’. The presence of triglycerides, characteristic of adipocytes, was revealed by staining with oil red O. Calcium deposition, indicative of osteoblasts, was stained with Von Kossa stain. (B) MSCs derived from C57BL/6 mice were stained with commercially available antibodies to analysis the surface marker by flow cytometry (red). Corresponding antibodies of the same isotype were used as controls (white). (C) C57BL/6 MSCs (1 × 106) were pretreated with proinflammatory 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 C57BL/6 mice armpit area. After 14 days of implantation, the animals were sacrificed and tumours were dissected. The weight and volume of B16 tumours were measured. The weight of tumour were measured after been removed from the mice. (*P < 0.05).

Mentions: MSCs adhered to the plastic surface, presenting a small population of single cells which were spindle-shaped and contained one nucleus after 72 hrs of the primary culture. During 7 to 10 days after the initial plating, the cells looked like long spindle-shaped fibroblastic cells and began to form colonies. MSCs could differentiate into adipocytes and osteoblast-like cells. The surface antigen profile of mouse MSCs was detected by flow cytometry was positive for CD90, CD105 and CD29 and negative for CD34 and CD45 (Fig. 1A, B)


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)

MSCs treated with proinflammatory cytokines favour the growth of tumour. (A) MSCs at passage 8 were grown under different conditions that favour differentiation into either adipocytes (for 14 days), or osteoblasts (for 14 days), as described in ‘Materials and methods’. The presence of triglycerides, characteristic of adipocytes, was revealed by staining with oil red O. Calcium deposition, indicative of osteoblasts, was stained with Von Kossa stain. (B) MSCs derived from C57BL/6 mice were stained with commercially available antibodies to analysis the surface marker by flow cytometry (red). Corresponding antibodies of the same isotype were used as controls (white). (C) C57BL/6 MSCs (1 × 106) were pretreated with proinflammatory 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 C57BL/6 mice armpit area. After 14 days of implantation, the animals were sacrificed and tumours were dissected. The weight and volume of B16 tumours were measured. The weight of tumour were measured after been removed from the mice. (*P < 0.05).
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Related In: Results  -  Collection

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fig01: MSCs treated with proinflammatory cytokines favour the growth of tumour. (A) MSCs at passage 8 were grown under different conditions that favour differentiation into either adipocytes (for 14 days), or osteoblasts (for 14 days), as described in ‘Materials and methods’. The presence of triglycerides, characteristic of adipocytes, was revealed by staining with oil red O. Calcium deposition, indicative of osteoblasts, was stained with Von Kossa stain. (B) MSCs derived from C57BL/6 mice were stained with commercially available antibodies to analysis the surface marker by flow cytometry (red). Corresponding antibodies of the same isotype were used as controls (white). (C) C57BL/6 MSCs (1 × 106) were pretreated with proinflammatory 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 C57BL/6 mice armpit area. After 14 days of implantation, the animals were sacrificed and tumours were dissected. The weight and volume of B16 tumours were measured. The weight of tumour were measured after been removed from the mice. (*P < 0.05).
Mentions: MSCs adhered to the plastic surface, presenting a small population of single cells which were spindle-shaped and contained one nucleus after 72 hrs of the primary culture. During 7 to 10 days after the initial plating, the cells looked like long spindle-shaped fibroblastic cells and began to form colonies. MSCs could differentiate into adipocytes and osteoblast-like cells. The surface antigen profile of mouse MSCs was detected by flow cytometry was positive for CD90, CD105 and CD29 and negative for CD34 and CD45 (Fig. 1A, B)

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