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Myocardio humano diseñado con maduración avanzada para aplicaciones en el modelado y la reparación de insuficiencia

Malte Tiburcy¹, James E Hudson¹, Paul Balfanz¹

¹From Institute of Pharmacology and Toxicology, University Medical Center Göttingen, Germany (M.T., J.E.H., P.B., S.S., T.M., M.-L.C.L., E.L., F.R., S.Z., E. Wettwer, W.-H.Z.); German Center for Cardiovascular Research (DZHK), partner site Göttingen, Germany (M.T., J.E.H., P.B., S.S., T.M., M.-L.C.L., E.L., F.R., S.Z., E. Wingender, W.A.L., W.-H.Z.); Institute of Bioinformatics, University Medical Center Göttingen, Germany (S.Z., E. Wingender); Stanford Cardiovascular Institute (J.R., M.W., J.D.G., J.C.W.) and Department of Radiology (J.D.G., J.C.W.), Molecular Imaging Program, Stanford University School of Medicine, CA; The Sohnis Laboratory for Cardiac Electrophysiology and Regenerative Medicine, Technion-Israel Institute of Technology, Haifa (I.K., L.G.); Institute of Pharmacology and Toxicology, Technical University Dresden, Germany (E. Wettwer, U.R.); University Medical Center Utrecht and Hubrecht Institute, The Netherlands (P.D., L.W.v.L.); Leiden University Medical Center, The Netherlands (M.J.G.); Clinic for Cardiology and Pneumology, University Medical Center Göttingen, Germany (S.K., K.T., G.H., W.A.L.); Center for Applied Technology, Beckman Research Institute, City of Hope, Duarte, CA (L.A.C.); Department of Cardiovascular Physiology, Institute of Physiology, Ruhr University Bochum, Bochum, Germany (A.U., W.A.L.); New Laura and Isaac Perlmutter Cancer Center at New York University Langone (T.A., B.N.); and McEwen Centre for Regenerative Medicine, Toronto, Canada (G.K.). The current address for Dr Hudson is Laboratory for Cardiac Regeneration, School of Biomedical Sciences, The University of Queensland, Australia.

|February 8, 2017

Resumen

Este estudio desarrolló miocardio humano de ingeniería (EHM) a partir de células madre, logrando una función similar a la de los adultos para la reparación del corazón y el modelado de enfermedades. La tecnología EHM escalable es prometedora para aplicaciones clínicas.

Área de la Ciencia:

Ingeniería cardiovascular
Biología de las células madre
La Medicina Regenerativa

Sus antecedentes:

Los cardiomiocitos derivados de células madre requieren una mayor maduración para su uso efectivo en aplicaciones cardíacas.
Los métodos actuales se enfrentan a desafíos para lograr propiedades estructurales y funcionales similares a las de los adultos.

Objetivo del estudio:

Para avanzar en la maduración de los cardiomiocitos derivados de células madre dentro del miocardio humano modificado.
Obtener un fenotipo similar al adulto en la EMH bajo condiciones definidas libres de suero.

Principales métodos:

Investigación sistemática de la composición celular, la matriz y los medios para la generación de EHM.
Se utilizaron cardiomiocitos y fibroblastos derivados de células madre pluripotentes embrionarias e inducidas.
Utilizó análisis morfológicos, funcionales y transcriptómicos para evaluar la maduración.

Principales resultados:

EHM exhibió propiedades estructurales y funcionales del miocardio postnatal, incluidos los cardiomiocitos en forma de varilla, fuerzas contráctiles significativas y una respuesta positiva de fuerza-frecuencia.
Se ha demostrado la señalización canónica β-adrenérgica y la respuesta a la toxicidad de las catecolaminas, imitando las características de la insuficiencia cardíaca.
Demostró la escalabilidad de EHM para las posibles demandas clínicas de reparación cardíaca.

Conclusiones:

Prueba de concepto para una tecnología universalmente aplicable para diseñar el miocardio humano a gran escala.
La EHM derivada de células madre en condiciones definidas y libres de suero es adecuada para el modelado de enfermedades y la reparación del corazón.

Palabras clave:

insuficiencia cardíaca Modelos de enfermedad cardiovascular regeneración Células madre ingeniería de tejidos

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