Novel tissue engineering strategies based on the combination of polymeric devices and adult stem cells for cardiac repair

  1. Díaz Herráez, Paula
Dirigida por:
  1. María José Blanco Prieto Directora
  2. Elisa Garbayo Atienza Codirectora

Universidad de defensa: Universidad de Navarra

Fecha de defensa: 09 de octubre de 2015

Tribunal:
  1. María del Rocío Herrero Vanrell Presidente/a
  2. Aránzazu Gonzalez Miqueo Secretario/a
  3. Manuel María Mazo Vega Vocal
  4. María de los Reyes Elizalde González Vocal
  5. Pieter Jelle Dijkstra Vocal
Departamento:
  1. (FFN) Ciencias Farmacéuticas

Tipo: Tesis

Teseo: 120222 DIALNET lock_openDadun editor

Resumen

Cardiovascular diseases (CVD) are the leading cause of death worldwide. Among them, myocardial infarction (MI) is the main CVDs, causing 7.4 million deaths each year. The current therapies for MI are palliative rather than regenerative. Since that, the tissue engineering (TE) strategy has grown investigators attention. With the aim of improving heart repair after MI, we have developed two TE strategies. The first strategy was the use of poly(lactic co-glycolic acid) (PLGA) microparticles (MPs) containing neuregulin (NRG), as support for attaching adipose-derived stem cells (ADSC): ADSC-NRG-MP. The second strategy was the combination of two different polymeric devices, MPs and hydrogels. The MPs loaded with NRG were embedded together with the ADSCs in hydrogels composed of different ratios of dextran (Dex) and hyaluronic acid (HA). Our hypothesis was that the developed systems would increase cell survival and would activate different pathways to favor heart regeneration. The ADSC-NRG-MP induced a more pronounced regeneration of the infarcted heart in a rat MI model (reduction in infarct size, higher left ventricle thickness and vasculogenesis). Also the employment of MPs as support for the ADSC, favored a long-term survival of the cells once in the tissue, being detectable three months after their administration. Moreover, among the hydrogels developed, the 50:50 Dex:HA hydrogel embedding 1 mg of NRG-MP and 500,000 ADSC showed to present the best characteristics (adequate stiffness for heart administration, prolonged gelation time to allow its injectability and degradation rate to allow cell survival). To conclude, the two strategies developed have shown to be promising candidates for heart repair after a MI.