title: Nanoprecipitated catestatin released from pharmacologically active microcarriers (PAMs) exerts pro-survival effects on MSC.
abstract: Catestatin (CST), a fragment of Chromogranin-A, exerts angiogenic, arteriogenic, vasculogenic and cardioprotective effects. CST is a very promising agent for revascularization purposes, in "NOOPTION" patients. However, peptides have a very short half-life after administration and must be conveniently protected. Fibronectin-coated pharmacologically active microcarriers (FN-PAM), are biodegradable and biocompatible polymeric microspheres that can convey mesenchymal stem cell (MSCs) and therapeutic proteins delivered in a prolonged manner. In this study, we first evaluated whether a small peptide such as CST could be nanoprecipitated and incorporated within FN-PAMs. Subsequently, whether CST may be released in a prolonged manner by functionalized FN-PAMs (FN-PAM-CST). Finally, we assessed the effect of CST released by FN-PAM-CST on the survival of MSCs under stress conditions of hypoxia-reoxygenation. An experimental design, modifying three key parameters (ionic strength, mixing and centrifugation time) of protein nanoprecipitation, was used to define the optimum condition for CST. An optimal nanoprecipitation yield of 76% was obtained allowing encapsulation of solid CST within FN-PAM-CST, which released CST in a prolonged manner. In vitro, MSCs adhered to FN-PAMs, and the controlled release of CST from FN-PAM-CST greatly limited hypoxic MSC-death and enhanced MSC-survival in post-hypoxic environment. These results suggest that FN-PAM-CST are promising tools for cell-therapy.
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Torino, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Angotti
authors.affiliation: INSERM U 1066, Micro et Nanomédecines biomimétiques - MINT, Angers, France; Université Angers, UMR-S1066 Angers, France.
authors.forename: M C
authors.initials: MC
authors.lastname: Venier-Julienne
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Torino, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Penna
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Torino, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Femminò
authors.affiliation: INSERM U 1066, Micro et Nanomédecines biomimétiques - MINT, Angers, France; Université Angers, UMR-S1066 Angers, France.
authors.forename: L
authors.initials: L
authors.lastname: Sindji
authors.affiliation: Artificial Biopolymers Department, Institut des Biomolecules Max Mousseron (IBMM) UMR5247, CNRS, University of Montpellier, ENSCM, Montpellier, France.
authors.forename: C
authors.initials: C
authors.lastname: Paniagua
authors.affiliation: INSERM U 1066, Micro et Nanomédecines biomimétiques - MINT, Angers, France; Université Angers, UMR-S1066 Angers, France.
authors.forename: C N
authors.initials: CN
authors.lastname: Montero-Menei
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Torino, Italy. Electronic address: pasquale.pagliaro@unito.it.
authors.forename: P
authors.initials: P
authors.lastname: Pagliaro
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry; D002454:Cell Differentiation; D053379:Chromogranin A / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*
chemical_list: D001672:Biocompatible Materials; D053379:Chromogranin A; D004337:Drug Carriers; D010446:Peptide Fragments; C109084:chromogranin A (344-364)
keywords: Catestatin; Drug delivery; Hypoxia; Mesenchymal stem cells; Microcarriers