title: Adipose-derived stem cells combined with neuregulin-1 delivery systems for heart tissue engineering.
abstract: Myocardial infarction (MI) is the leading cause of death worldwide, and extensive research has therefore been performed to find a cure. Neuregulin-1 (NRG) is a growth factor involved in cardiac repair after MI. We previously described how biocompatible and biodegradable microparticles, which are able to release NRG in a sustained manner, represent a valuable approach to avoid problems related to the short half-life after systemic administration of proteins. The effectiveness of this strategy could be improved by combining NRG with several cytokines involved in cardiac regeneration. The present study investigates the potential feasibility of using NRG-releasing particle scaffold combined with adipose-derived stem cells (ADSC) as a multiple growth factor delivery-based tissue engineering strategy for implantation in the infarcted myocardium. NRG-releasing particle scaffolds with a suitable size for intramyocardial implantation were prepared by TROMS. Next, ADSC were adhered to particle scaffolds and their potential for heart administration was assessed in a MI rat model. NRG was successfully encapsulated reaching encapsulation efficiencies of 92.58 ± 3.84%. NRG maintained its biological activity after the microencapsulation process. ADSCs adhered efficiently to particle scaffolds within a few hours. The ADSC-cytokine delivery system developed proved to be compatible with intramyocardial administration in terms of injectability through a 23-gauge needle and tissue response. Interestingly, ADSC-scaffolds were present in the peri-infarted tissue 2 weeks after implantation. This proof of concept study provides important evidence required for future effectiveness studies and for the translation of this approach.
authors: Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra, Pamplona, Spain.
authors: P
authors: P
authors: Díaz-Herráez
authors: E
authors: E
authors: Garbayo
authors: T
authors: T
authors: Simón-Yarza
authors: F R
authors: FR
authors: Formiga
authors: F
authors: F
authors: Prosper
authors: M J
authors: MJ
authors: Blanco-Prieto
mesh_terms: D050153:Abdominal Fat / Q000166:cytology*; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000009:adverse effects; D005240:Feasibility Studies; D005549:Foreign-Body Reaction / Q000517:prevention & control; D006133:Growth Substances / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics / Q000627:therapeutic use; D048091:Guided Tissue Regeneration / Q000009:adverse effects; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D015552:Injections, Intralesional; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D020890:Neuregulin-1 / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012038:Regeneration / Q000187:drug effects; D033581:Stem Cell Transplantation / Q000009:adverse effects; D054457:Tissue Scaffolds / Q000009:adverse effects / Q000737:chemistry
chemical_list: D006133:Growth Substances; C094131:NRG1 protein, human; D020890:Neuregulin-1; D011994:Recombinant Proteins
keywords: ADSC; Cardiac repair; Myocardial infarction; NRG-1; PLGA microparticles; Particle scaffold