Fachbereich Veterinärmedizin



    Autologe mesenchymale Stromazellen im Ischämie/Reperfusions-induzierten akuten Nierenversagen im Schweinemodell (2013)

    Boche, Janna (WE 12)
    Berlin: Mensch und Buch Verlag, 2013 — 161 Seiten
    ISBN: 978-3-86387-269-4
    URL (Volltext): http://www.diss.fu-berlin.de/diss/receive/FUDISS_thesis_000000093975
    Institut für Tierpathologie

    Robert-von-Ostertag-Str. 15
    Gebäude 12
    14163 Berlin
    +49 30 838 62450

    Abstract / Zusammenfassung

    It could previously be demonstrated in the rat model of acute kidney injury that treatment with mesenchymal stromal cells (MSCs) has a protective effect on kidney functioning and accelerates the healing process through complex paracrine mechanisms.
    In order to obtain preparatory data for future clinical studies with human patients, the kidney protecting effect of MSC in acute kidney injury was tested in a porcine model. For the induction of acute kidney injury in pigs a method was established in which through bilateral balloon catheter technique via the Aa. femorales into the Aa. renales a reversible ischemia was induced. After an occlusion time of 110 minutes for the induction of the acute kidney injury, eight female pigs were infused with autologuous MSC into the supra aorta, a control group consisting of seven animals was just infused with medium. Through the determination of biological parameters (i.e. creatinine, urea) in blood and urine the progression of the kidney injury was monitored over four weeks.
    After the killing of the pigs tissue was taken and examined morphologically and histologically. There were no acute or subsequent complications after the transplantation of MSC, but the beneficial effect of MCS on kidney function and histology from the rat model could not be demonstrated.
    The MSC were plastic adherent, differentiated in adipocytes, chondrocytes and osteoblasts, showed the characteristic antigen profile (CD 90, CD 105 and MHCI positive and CD 14 and CD 45 negative) and therefore fulfilled all the criteria of mesenchymal stromal cells.
    It can be concluded from the data of the mixed lymphocyte reaction (MLR) that porcine MSC have a different immune response than human MSC. In vitro, they are not able to suppress a T-lymphocyte activation and proliferation through cellular or unspecific mitogen stimuli.
    However, since the inflammation in the pathophysiology plays an important role in acute kidney injury, the inadequate immune-modulating effect could be the reason for the fact that the porcine MSC did not show any improvement of kidney function and a successful therapy is possibly dependent on the anti-inflammatory effect.
    Consequently, the treatment of acute kidney injury in this large animal model did not provide any information in relation to the underlying mechanisms.
    It can be hoped that the treatment of acute kidney injury in humans with MCS could be equally successful as in the rodent model, due to its immune-modulating effect.