Limbusstammzellen und ihre Nische: Bedeutung für biotechnologischen Gewebeersatz

Zusammenfassung

Reparatur- und Regenerationsvorgänge des Hornhautepithels werden aus einem Reservoir unipotenter Progenitorzellen gespeist, welche in der basalen Epithelschicht am korneoskleralen Limbus lokalisiert sind. Geht diese Zellpopulation verloren, kommt es zu Störungen der Oberflächenintegrität, mit der möglichen Folge eines schmerzhaften Sehverlusts. Zur Therapie werden seit Ende der 1990er-Jahre kultivierte limbale Epithelzellen klinisch angewandt. Hierzu werden Limbusepithelzellen aus dem Partnerauge oder aus Spendergewebe entnommen, im Labor auf unterschiedlichen Trägern vermehrt und anschließend transplantiert. Dieser Vorgang entfernt die Progenitorzellen aus ihrem natürlich vorherrschenden Milieu. Jedoch herrscht weitgehend Konsens, dass umgebende Zellen und extrazelluläre Matrix wichtige Stimuli zur Verfügung stellen, welche für den Erhalt der Stammzelleigenschaften und für eine korrekte Ausdifferenzierung erforderlich sind. Neuere Ansätze versuchen daher, diese sogenannte „Stammzellnische“ auch ex vivo und nach erfolgter Transplantation bereitzustellen. Zugleich können Nischenfaktoren die Transdifferenzierung alternativer Progenitorzelltypen zu einem kornealen Phänotyp unterstützen und ermöglichen somit den Einsatz autologer Zellen auch bei beidseitiger Insuffizienz der Limbusregion. Für die Kultivierung, Transdifferenzierung und Transplantation der Spenderzellen wurden diverse biosynthetische Träger entwickelt. Die vorliegende Arbeit soll einen Überblick über die bislang verfügbaren und zum Teil klinisch angewendeten Konstrukte geben. Zusätzlich werden in der Entwicklung befindliche Konzepte zusammengefasst, welche mittels Integration putativer Nischenfaktoren in das Stammzell-Trägerkonstrukt eine Replikation der Stammzellnische erreichen sollen.

Abstract

Regeneration and repair of corneal epithelium rely on a reservoir of unipotent progenitor cells, which is situated within the basal epithelial layer at the corneoscleral limbus. If these cells are lost, corneal surface integrity is disturbed, which may lead to a painful loss of vision. Since the late 1990s cultivated grafts of limbal epithelium are being used therapeutically. Limbal epithelial cells are obtained from the fellow eye or from an allogeneic donor, propagated in culture on different types of carriers, and subsequently transplanted. This process entails removal of progenitor cells from their natural environment. However, surrounding cells and extracellular matrix are widely believed to provide important stimuli for stem cell maintenance and for correct differentiation. Therefore, new approaches aim at providing this so-called stem cell niche ex vivo and following transplantation. Niche factors can also drive transdifferentiation of alternative progenitor cell types towards a corneal phenotype. This permits the use of autologous cells in cases of bilateral limbal stem cell insufficiency. Several biosynthetic substrates have been devised for culture, transdifferentiation and transplantation of donor cells. This work intends to provide an overview of constructs that are currently available and to some extent clinically employed. In addition, a summary is given of novel concepts which aim at integrating putative niche factors into the stem cell carriers to replicate the stem cell niche.

Schlüsselwörter

Limbusstammzellen - Stammzellnische - Cornea - Tissue engineering

Key words

limbal stem cells - stem cell niche - cornea - tissue engineering

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