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Regeneración del alvéolo pulmonar por un progenitor epitelial conservado evolutivamente

William J Zacharias^1,2, David B Frank^2,3,4, Jarod A Zepp^1,2

¹Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

|March 1, 2018

Resumen

Los investigadores descubrieron un linaje específico de células epiteliales alveolares (AEP) en el pulmón. Estos AEP son cruciales para la regeneración del tejido pulmonar después de la lesión y ofrecen un nuevo objetivo para las terapias de regeneración pulmonar.

Área de la Ciencia:

Medicina de los pulmones
Biología Regenerativa
Biología celular

Sus antecedentes:

La regeneración funcional del tejido es vital para la homeostasis del órgano después de la lesión.
Los órganos en reposo como el pulmón dependen de células progenitoras facultativas para la regeneración.
La identificación de células progenitoras específicas es clave para comprender los mecanismos de reparación pulmonar.

Objetivo del estudio:

Identificar y caracterizar las células progenitoras facultativas del pulmón distal responsables de la regeneración.
Investigar el papel de las células epiteliales alveolares (AEP) sensibles a Wnt en la reparación pulmonar.
Determinar si las AEP humanas pueden aislarse y utilizarse para estrategias regenerativas.

Principales métodos:

Profilación transcriptómica y epigenómica de las células epiteliales alveolares progenitoras.
Estudios in vivo de la expansión del linaje AEP después de una lesión pulmonar aguda.
Aislamiento y evaluación funcional de las AEP humanas utilizando modelos organoides tridimensionales.
Análisis de la participación de las vías de señalización Wnt y Fgf.

Principales resultados:

Se identificó un linaje progenitor epitelial alveolar (AEP) sensible a Wnt dentro de las células alveolares de tipo 2.
Las AEP son estables durante la homeostasis, pero se expanden significativamente para regenerar el epitelio alveolar después de la lesión.
Las AEP poseen un perfil molecular y funcional distinto, respondiendo a las señales Wnt y Fgf.
Las AEP humanas se aislaron utilizando el marcador TM4SF1 y demostraron capacidad regenerativa en organoides.

Conclusiones:

El linaje AEP representa una célula progenitora facultativa importante en el pulmón distal.
Este linaje se conserva evolutivamente y juega un papel crítico en la regeneración pulmonar.
La orientación de los AEP ofrece una nueva vía prometedora para las estrategias de regeneración pulmonar humana.

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