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Zellbasierte Strategien für die Speicheldrüsenregeneration

Cell-based strategies for salivary gland regeneration

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Zusammenfassung

Die Xerostomie nach Bestrahlung oder bei M. Sjögren führt zu schwerwiegenden Einschränkungen der Lebensqualität der betroffenen Patienten. Präventive Therapieansätze wie die intensitätsmodulierte Strahlentherapie, die chirurgische Verlagerung einer Gl. submandibularis aus dem Strahlenfeld oder die Gabe von Amifostin während der Bestrahlung sind noch nicht klinisch etabliert und auch nicht für alle Patienten einsetzbar. Die symptomatische Therapie mit Pilocarpin oder künstlichem Speichel führt nur bei einem Teil der Patienten zur Besserung der Symptome und weist im Falle von Pilocarpin bedeutsame systemische anticholinerge Nebenwirkungen auf. Aufgrund der Vielzahl der betroffenen Patienten und der ungenügenden Therapieoptionen ist die Entwicklung neuer Therapieformen von großer Bedeutung. Neben der In-vitro-Herstellung von funktionellen Speicheldrüsenkonstrukten mit Tissue-Engineering-Verfahren wird gegenwärtig versucht, durch gentherapeutische Ansätze, die die Transfektion der betroffenen Speicheldrüsen mit Aquaporinen oder gefäßwachstuminduzierenden Faktoren umfasst, die eingeschränkte Speicheldrüsenfunktion experimentell zu therapieren. Darüber hinaus wird die Applikation von Stammzellen in vivo als weitere Therapieoption diskutiert und analysiert. Im vorliegenden Artikel wird der klinische und strahlenbiologische Hintergrund der Xerostomie erläutert und die angesprochenen neuen Therapieansätze dargestellt und diskutiert.

Abstract

Xerostomia as a side effect of radiotherapy or due to Sjögren’s disease leads to considerable impairment of the quality of life of the affected patients. Preventive treatment approaches such as intensity-modulated radiotherapy, surgical transfer of a submandibular gland to a site outside the radiation field or administration of amifostin during radiation treatment are not yet completely established in clinical practice and are not applicable for all patients. Symptomatic treatment with pilocarpin or synthetic saliva leads to an improvement of the symptoms only in some patients, and in the case of pilocarpin significant systemic anticholinergic side-effects might occur. Because large numbers of patients are affected and current treatment options are not satisfactory, it is essential to develop new treatment options. In parallel with the in vitro production of functional salivary gland constructs by means of tissue engineering techniques, attempts are currently under way to experimentally restore salivary gland function by genetic treatment approaches such as transfection of the affected salivary glands with aquaporins or pro-angiogenic factors. In addition, the in vivo application of stem cells is under investigation. In the present paper, we discuss the clinical and radiobiological background of xerostomia and highlight possible innovative future treatment options.

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Danksagung

Unterstützt durch die Novartis-Stiftung für Therapeutische Forschung sowie durch den Schwerpunkt „Regenerative Medizin“ der Universität Lübeck.

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Rotter, N., Wirz, C., Oder, J. et al. Zellbasierte Strategien für die Speicheldrüsenregeneration. HNO 56, 281–287 (2008). https://doi.org/10.1007/s00106-007-1650-5

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