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Volume 18 Supplement 2

Sepsis 2014

Effects of mesenchymal stromal cells on human umbilical vein endothelial cells in in vitro sepsis models

Introduction

Septic shock is a medical emergency that, despite the medical advances that have been made, still remains a major cause of hospital deaths. Cell therapy is an innovative field of research that could provide a therapy for sepsis. Mesenchymal stromal cells (MSC) are promising in cell therapy and more importantly for sepsis because of their immunosuppressive capabilities [1]. MSC have been shown by several groups to have a positive effect against sepsis in vivo [24]. It has been predicted that the MSC interact with macrophage to release IL-10 that in turns reduces inflammation [4]. Other groups have focused on the use of stimulated MSC to ameliorate their immunosuppressive capabilities [5]. The main stimulation of MSC has been the use of inflammatory stimulants like IFNγ. Our work focuses on the identification of effective MSC donors, whether primed with IFNγ or naïve, and the development of in vitro models that will predict how an MSC donor will act in vivo. We also want to eliminate the use of cells completely and use their secreted microvesicles as a therapy. The hypothesis is that the in vitro models will eliminate a noneffective MSC donor and allow us to identify the MSC donor that will have the greatest effect.

Methods

We developed two in vitro models that are similar to what happens in vivo with WBC as they circulate in a septic patient. The first test is the adherence of WBC to a layer of HUVECs in the presence of MSC or microvesicles. The second is a permeability test to determine MSC ability to block the permeability of a HUVEC layer.

Results

Our preliminary results have shown that we are able to identify, using our two in vitro models, which MSC donor would be an effective MSC for cell therapy.

Conclusion

MSC and their paracrine factors have to the potential to be an effective therapy for sepsis, but one needs to identify an effective donor before use in cell therapy.

References

  1. 1.

    Meirelles L, Fontes AM, Covas DT, et al.: Mechanisms involved in the therapeutic properties of mesenchymal stem cells. Cytokine Growth Factor Rev 2009, 20: 419-427. 10.1016/j.cytogfr.2009.10.002

    CAS  Article  Google Scholar 

  2. 2.

    Gonzalez-Rey E, Anderson P, Gonzalez MA, et al.: Human adult stem cells derived from adipose tissue protect against experimental colitis and sepsis. Gut 2009, 58: 929-939. 10.1136/gut.2008.168534

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Hall SR, Tsoyi K, Ith B, et al.: Mesenchymal stromal cells improve survival during sepsis in the absence of heme oxygenase-1: the importance of neutrophils. Stem Cells 2012, 31: 397-407.

    Article  Google Scholar 

  4. 4.

    Nemeth K, Leelahavanichkul A, Yuen PS, et al.: Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat Med 2009, 15: 42-49. 10.1038/nm.1905

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Polchert D, Sobinsky J, Douglas G, et al.: IFN-gamma activation of mesenchymal stem cells for treatment and prevention of graft versus host disease. Eur J Immunol 2008, 38: 1745-1755. 10.1002/eji.200738129

    CAS  Article  PubMed  PubMed Central  Google Scholar 

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Correspondence to K Lund.

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Lund, K., Peltzer, J., Montespan, F. et al. Effects of mesenchymal stromal cells on human umbilical vein endothelial cells in in vitro sepsis models. Crit Care 18, P72 (2014). https://doi.org/10.1186/cc14075

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Keywords

  • Septic Shock
  • Cell Therapy
  • Human Umbilical Vein Endothelial Cell
  • Effective Therapy
  • Umbilical Vein