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Mesenchymale Stromazellen und ihre Nische

Mesenchymal stroma cells and their niche

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Zusammenfassung

Stammzellen leben in einem hochspezialisierten Mikromilieu, das als Stammzellnische bezeichnet wird. Die Stammzellnische kann vereinfacht umschrieben werden als anatomisch definierter Raum, in dem die Stammzelle lokalisiert ist, ernährt und die Homöostase des Stammzellpools über Stammzellproliferation und -differenzierung reguliert wird. Ein primäres Ziel des Tissue Engineering ist es, die Stammzellnische zu imitieren, um entweder die Differenzierung der Stammzelle in eine bestimmte Richtung zu induzieren, ihr Selbsterneuerungspotenzial zu erhalten oder beide Eigenschaften in einem ausbalancierten Verhältnis zu wahren.

Mesenchymale Stamm-/Stromazellen („mesenchymal stem cells“, MSC) können in einem phosphatreichen Kultivierungsmileu in einer 3-D-kollagenreichen Matrix in Osteoblasten differenzieren und einen prosynthetischen, matrixremodellierenden Phänotyp akquirieren. Da es im Rahmen der Gefäßverkalkung beim niereninsuffizienten Patienten auch zu einer ausgeprägten Matrixremodellierung mit Verkalkung kommt, wurde der Einfluss der Urämie als pathophysiologischer Stimulus auf MSC und Endothelzellen untersucht. Die Ergebnisse stellen klar, dass BMP-2/4-vermittelt in der Urämie eine osteogene (Mal)Differenzierung der MSC mit ausgeprägter Matrixverkalkung eintritt und MSC ihre proangiogenen Eigenschaften verlieren, sodass keine Nischenfunktion für Endothelzellen aufgebaut werden kann. Die Arbeiten lassen den Schluss zu, dass die Urämie die Stammzellnische zerstört und eine fortschreitende Gefäßverkalkung durch osteogene (Mal)Differenzierung der MSC beeinflussen kann.

So kann die Stammzellnische Stammzelleigenschaften dirigieren und ihre Nachahmung kann in vitro für das Tissue Engineering genutzt werden, jedoch scheint die Stammzellnische unter pathophysiologischen Bedingungen entscheidend zur Pathogenese einer Erkrankung beitragen zu können.

Abstract

Stem cells reside in a highly specialized, complex microenvironment that is known as the stem cell niche. The stem cell niche can be described as an anatomically defined space where the stem cell is localized and nourished and stem cell quiescence, proliferation and differentiation are maintained. Tissue engineering aims to imitate the stem cell niche to (I) induce a directed differentiation, (II) maintain the self-renewal capacity or (III) find a regulated balance between self-renewal and differentiation. Mesenchymal stem or stromal cells (MSC) can differentiate in three-dimensional collagen gels into functional osteoblasts when subjected to a phosphate-rich cultivation medium. Furthermore, they acquire a prosynthetic, matrix remodeling, contractile phenotype. Medial artery calcification in patients with chronic kidney disease also proceeds through intramembranous ossification resulting from osteoblast-induced calcification of the collagen extracellular matrix. Thus, the influence of uremic cultivation conditions as a pathophysiological stimulus on MSC and endothelial cells was analyzed with special regards to matrix remodeling, vascularization and calcification. The results showed that BMP-2/4 mediated MSC (mal)differentiation into osteoblasts with acquired matrix remodeling phenotype and loss of proangiogenic capacity. These studies have led to the conclusion that uremia has detrimental effects on the stem cell niche and promotes the continuous calcification by osteogenic (mal)differentiation. In summary, recent studies have shown the conducting and regulating effect of the stem cell niche under physiological conditions that can be applied and mimicked for tissue engineering applications. However, under pathological conditions the stem cell niche can have detrimental effects on stem cell function and can promote disease progression.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. R.K. Schneider gibt an, dass kein Interessenkonflikt besteht. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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  1. Institut für Pathologie, Universitätsklinikum RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Deutschland

    R.K. Schneider

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Schneider, R. Mesenchymale Stromazellen und ihre Nische. Pathologe 34 (Suppl 2), 264–268 (2013). https://doi.org/10.1007/s00292-013-1818-6

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