The effects of EPO on cutaneous wound healing, dermal stem cell marker activation, and gene expression patterns

Publikation: Qualifikations-/StudienabschlussarbeitDissertation

Autoren

  • Meimanat Fathi

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OriginalspracheEnglisch
QualifikationDoctor rerum naturalium
Gradverleihende Hochschule
Betreut von
Datum der Verleihung des Grades22 Feb. 2023
ErscheinungsortHannover
PublikationsstatusVeröffentlicht - 2023

Abstract

Narben wirken sich oft negativ auf die individuelle Selbstwahrnehmung von Schönheit, Lebensqualität und Selbstvertrauen aus. Um diese negativen Auswirkungen zu verringern, versuchen Forscher die biologischen Mechanismen, die zur Narbenbildung führen, besser zu verstehen, damit wirksamere klinische Behandlungen entwickelt werden können. Langfristige Ziele sind die Hautregeneration zu beschleunigen und die narbenlose Heilung von Wundverletzungen. In früheren Studien haben Forscher gezeigt, dass niedrig dosiertes Erythropoietin (EPO) regenerative und zytoprotektive Wirkungen in präklinischen Tiermodellen und sogar bei klinischen Patienten mit Verbrennungen oder diabetischen Wunden hat. Allerdings sind die molekularen Mechanismen, durch die EPO die Narbenbildung und/oder Wundheilung im menschlichen Hautgewebe beeinflusst, unklar. Daher werden in diesem Forschungsprojekt die Wirkung von EPO auf die Wundheilung von Hauttransplantaten beim menschlichen Patienten mit immunhistochemischen Methoden untersucht, und dann zusätzliche In-vitro-Experimente durchgeführt, um zu prüfen, wie die Wirkung von EPO durch das Vorhandensein anderer kleiner Moleküle, sogenannter proinflammatorischer Zytokine, beeinflusst wird. Im Einzelnen wurde in einer Studie (i) die Wirkung einer systemischen Anwendung von EPO auf immunhistochemische Indikatoren der Wundheilung anhand von Hautproben aus einer klinischen Studie untersucht, bei der EPO-behandelte Gruppen mit Placebo-behandelten Gruppen verglichen wurden. In einer zweiten In-vitro Studie wurde: (ii) die Wirkung der EPO-Verabreichung (allein und in Kombination mit verschiedenen Zytokinen, z. B. IL-6, TNF-a) auf die Expressionsniveaus von Genen, die mit der Wundheilung in Verbindung stehen, getestet. In der ersten Studie ergaben die immunhistochemischen Analysen keine eindeutigen Muster, die die Behandlungs- und Kontrollgruppen unterschieden, mit Ausnahme des von-Willebrand-Faktor, der Anzeichen einer verringerten Expression in der der EPO-behandelten Gruppe zeigte. In der zweiten Studie führte die Verabreichung von EPO und die gleichzeitige Verabreichung von EPO mit den Zytokinen TNF-a und IL-6 zu einigen Veränderungen der Genexpression in den Mesenchymalen Stammzellen die aus der Vorhaut gewonnen wurden. Die Behandlung mit EPO allein und die gleichzeitige Verabreichung von EPO mit TNF-a und IL-6 führte jedoch nicht zu statistisch signifikanten Unterschieden in GO- oder KEGG-Signalwegen.

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The effects of EPO on cutaneous wound healing, dermal stem cell marker activation, and gene expression patterns. / Fathi, Meimanat.
Hannover, 2023. 86 S.

Publikation: Qualifikations-/StudienabschlussarbeitDissertation

Fathi, M 2023, 'The effects of EPO on cutaneous wound healing, dermal stem cell marker activation, and gene expression patterns', Doctor rerum naturalium, Gottfried Wilhelm Leibniz Universität Hannover, Hannover. https://doi.org/10.15488/13329
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