Beyond fibrosis: stellate cells as liver stem cells

Abstract

The high regenerative potential of the liver is driven by parenchymal and non-parenchymal cells, which restore the original liver mass after injury by cell proliferation. The contribution of stem- and progenitor cells to liver regeneration is mainly observed when hepatocyte proliferation is impaired. However, the origin of stem/progenitor cells and their effectivity to restore injured liver is currently discussed controversially. Hepatic stellate cells, which are mainly known for their contribution to fibrosis in chronic liver diseases, were recently identified as mesenchymal stem cells (MSC) of the liver. Stellate cells are also involved in liver regeneration and fulfill a dual function by supporting neighboring cells and developing into liver epithelial cells. This demonstrates that stellate cells not only exhibit the same expression profile and differentiation potential but also functional similarities to MSC of other organs, which are at present intensively studied by many groups for their therapeutic use in liver diseases.

Zusammenfassung

Die sehr gute Fähigkeit der Leber zur Regeneration wird von Parenchym- und Nicht-Parenchymzellen getragen, die nach einer Schädigung die ursprüngliche Lebermasse durch Zellteilung wiederherstellen. Eine Beteiligung von Stamm- und Progenitorzellen an regenerativen Prozessen der Leber wird v. a. bei einer inhibierten Proliferation von Hepatozyten beobachtet. Die Herkunft der Stamm-/Progenitorzellen und das Ausmaß ihrer Beteiligung an der Regeneration wird jedoch derzeit kontrovers diskutiert. Hepatische Sternzellen, die hauptsächlich durch ihre Beteiligung an der Entstehung einer Fibrose bei chronischen Erkrankungen der Leber bekannt sind, wurden kürzlich als mesenchymale Stammzellen (MSC) der Leber identifiziert. Sternzellen sind ebenfalls in die Regeneration der geschädigten Leber involviert und besitzen offensichtlich eine duale Funktion, indem sie einerseits benachbarte Zellen beeinflussen und andererseits epitheliale Zellen der Leber bilden können. Damit zeigen Sternzellen nicht nur ein Expressionsprofil und Differenzierungspotenzial, sondern auch funktionell eine hohe Übereinstimmung mit MSC anderer Organe, deren therapeutisches Potenzial zur Behandlung von Lebererkrankungen gegenwärtig von vielen Arbeitsgruppen untersucht wird.

Schlüsselwörter

mesenchymale Stammzellen - MSC - Sternzellen - Ovalzellen - Leberstammzellen - Leberregeneration

Key words

mesenchymal stem cells - MSC - stellate cells - oval cells - liver stem cells - liver regeneration

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