title: Preparation and characterization of collagen-based ADSC-carrier sheets for cardiovascular application.
abstract: The use of scaffolds composed of natural biodegradable matrices represents an attractive strategy to circumvent the lack of cell engraftment, a major limitation of stem cell therapy in cardiovascular diseases. Bovine-derived non-porous collagen scaffolds with different degrees of cross-linking (C0, C2, C5 and C10) were produced and tested for their mechanical behavior, in vitro biocompatibility with adipose-derived stem cells (ADSCs) and tissue adhesion and inflammatory reaction. Uniaxial tensile tests revealed an anisotropic behavior of collagen scaffolds (2×0.5cm) and statistically significant differences in the mechanical behavior between cross-linked and non-cross-linked scaffolds (n=5). In vitro, ADSCs adhered homogenously and showed a similar degree of proliferation on all four types of scaffolds (cells×10(3)cm(-2) at day 7: C0: 94.7±37.1; C2: 91.7±25.6; C5: 88.2±6.8; C10: 72.8±10.7; P=n.s.; n=3). In order to test the in vivo biocompatibility, a chronic myocardial infarction model was performed in rats and 1.2×1.2cm size collagen scaffolds implanted onto the heart 1month post-infarction. Six animals per group were killed 2, 7 and 30days after transplant. Complete and long-lasting adhesion to the heart was only observed with the non-cross-linked scaffolds with almost total degradation 1month post-transplantation. After 7 and 30days post-implantation, the degree of inflammation was significantly lower in the hearts treated with non-cross-linked scaffolds (day 7: C0: 10.2±2.1%; C2: 16.3±2.9%; C5: 15.9±4.8%; C10: 17.4±4.1%; P<0.05 vs. C0; day 30: C0: 1.3±1.3%; C2: 9.4±3.0%; C5: 7.0±2.1%; C10: 9.8±2.5%; P<0.01 vs. C0). In view of the results, the non-cross-linked scaffold (C0) was chosen as an ADSC-carrier sheet and tested in vivo. One week post-implantation, 25.3±7.0% of the cells transplanted were detected in those animals receiving the cell-carrier sheet whereas no cells were found in animals receiving cells alone (n=3 animals/group). We conclude that the biocompatibility and mechanical properties of the non-cross-linked collagen scaffolds make them a useful cell carrier that greatly favors tissue cell engraftment and may be exploited for cell transplantation in models of cardiac disease.
authors.affiliation: Laboratory of Cell Therapy, Division of Cancer, Foundation for Applied Medical Research, University of Navarra, Navarra, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Araña
authors.forename: Estefanía
authors.initials: E
authors.lastname: Peña
authors.forename: Gloria
authors.initials: G
authors.lastname: Abizanda
authors.forename: Myriam
authors.initials: M
authors.lastname: Cilla
authors.forename: Ignacio
authors.initials: I
authors.lastname: Ochoa
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Gavira
authors.forename: Gaudencio
authors.initials: G
authors.lastname: Espinosa
authors.forename: Manuel
authors.initials: M
authors.lastname: Doblaré
authors.forename: Beatriz
authors.initials: B
authors.lastname: Pelacho
authors.forename: Felipe
authors.initials: F
authors.lastname: Prosper
mesh_terms: D020341:Absorbable Implants; D017667:Adipocytes / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D024042:Collagen Type I / Q000737:chemistry*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005260:Female; D008422:Materials Testing; D009203:Myocardial Infarction / Q000473:pathology / Q000601:surgery*; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology*; D023822:Tissue Engineering / Q000295:instrumentation; D054457:Tissue Scaffolds; D016896:Treatment Outcome
chemical_list: D024042:Collagen Type I