Mesenchymal stem cells correct haemodynamic dysfunction associated with liver injury after extended resection in a pig model

间充质干细胞纠正猪模型中扩大切除后肝损伤相关的血流动力学功能障碍

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作者:Hans-Michael Tautenhahn, Sandra Brückner, Christiane Uder, Silvio Erler, Madlen Hempel, Martin von Bergen, Janine Brach, Sandra Winkler, Franziska Pankow, Claudia Gittel, Manja Baunack, Undine Lange, Johannes Broschewitz, Matthias Dollinger, Michael Bartels, Uta Pietsch, Kerstin Amann, Bruno Christ1

Abstract

In patients, acute kidney injury (AKI) is often due to haemodynamic impairment associated with hepatic decompensation following extended liver surgery. Mesenchymal stem cells (MSCs) supported tissue protection in a variety of acute and chronic diseases, and might hence ameliorate AKI induced by extended liver resection. Here, 70% liver resection was performed in male pigs. MSCs were infused through a central venous catheter and haemodynamic parameters as well as markers of acute kidney damage were monitored under intensive care conditions for 24 h post-surgery. Cytokine profiles were established to anticipate the MSCs' potential mode of action. After extended liver resection, hyperdynamic circulation, associated with hyponatraemia, hyperkalaemia, an increase in serum aldosterone and low urine production developed. These signs of hepatorenal dysfunction and haemodynamic impairment were corrected by MSC treatment. MSCs elevated PDGF levels in the serum, possibly contributing to circulatory homeostasis. Another 14 cytokines were increased in the kidney, most of which are known to support tissue regeneration. In conclusion, MSCs supported kidney and liver function after extended liver resection. They probably acted through paracrine mechanisms improving haemodynamics and tissue homeostasis. They might thus provide a promising strategy to prevent acute kidney injury in the context of post-surgery acute liver failure.

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