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Alivio de la diabetes en ratones por las células α humanas secretoras de insulina sensibles a la glucosa

Kenichiro Furuyama¹, Simona Chera^1,2, Léon van Gurp¹

¹Department of Genetic Medicine and Development, iGE3 and Centre Facultaire du Diabète, Faculty of Medicine, University of Geneva, Geneva, Switzerland.

|February 15, 2019

Resumen

Las células de los islotes humanos pueden cambiar de identidad para convertirse en células productoras de insulina, ofreciendo un nuevo tratamiento potencial para la diabetes. Esta plasticidad celular en el páncreas humano ofrece esperanza para la medicina regenerativa.

Área de la Ciencia:

Endocrinología
La Medicina Regenerativa
Biología celular

Sus antecedentes:

Los interruptores de identidad celular son una estrategia regenerativa conocida en los animales, pero poco comprendida en los mamíferos.
En ratones, las células alfa y delta pancreáticas pueden convertirse en células beta productoras de insulina después de la pérdida de células beta.
La plasticidad de las células de los islotes humanos, particularmente en la diabetes, sigue siendo en gran medida desconocida.

Objetivo del estudio:

Investigar si las células no beta de los islotes humanos (células alfa y gamma) presentan plasticidad.
Para determinar si estas células humanas pueden ser reprogramadas para producir insulina.
Evaluar el potencial terapéutico de las células de islotes humanos convertidas para el tratamiento de la diabetes.

Principales métodos:

Se rastrearon células de islotes humanos de donantes no diabéticos y diabéticos.
Las células no beta (células gamma productoras de alfa y PPY) fueron reprogramadas utilizando los factores de transcripción PDX1 y MAFA.
Se trasplantaron células convertidas en ratones diabéticos y se evaluó la producción de insulina y la reversión de la diabetes.
Se realizaron análisis transcriptómicos y proteómicos profundos en las células alfa productoras de insulina convertidas.

Principales resultados:

Las células alfa y gamma de los islotes humanos fueron reprogramadas con éxito para producir y secretar insulina en respuesta a la glucosa.
Las células alfa humanas convertidas trasplantadas revirtieron la diabetes en ratones y mantuvieron la producción de insulina durante al menos seis meses.
Las células alfa reprogramadas mantuvieron la expresión de marcadores de células alfa, lo que indica una identidad celular estable.
La caracterización molecular profunda confirmó la plasticidad y la función de las células convertidas.

Conclusiones:

Las células de los islotes humanos poseen plasticidad, lo que permite que las células no beta se conviertan en células funcionales productoras de insulina.
Esta reprogramación celular ofrece una vía prometedora para el tratamiento de la diabetes a través de la medicina regenerativa.
Los hallazgos proporcionan un marco molecular para comprender y utilizar la plasticidad celular in situ para el tratamiento de la diabetes y otras enfermedades degenerativas.

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