Abstract
The complex and highly organized environment in which cells reside consists primarily of the extracellular matrix (ECM) that delivers biological signals and physical stimuli to resident cells. In the native myocardium, the ECM contributes to both heart compliance and cardiomyocyte maturation and function. Thus, myocardium regeneration cannot be accomplished if cardiac ECM is not restored. We hypothesize that decellularized human skin might make an easily accessible and viable alternate biological scaffold for cardiac tissue engineering (CTE). To test our hypothesis, we decellularized specimens of both human skin and human myocardium and analyzed and compared their composition by histological methods and quantitative assays. Decellularized dermal matrix was then cut into 600-μm-thick sections and either tested by uniaxial tensile stretching to characterize its mechanical behavior or used as three-dimensional scaffold to assess its capability to support regeneration by resident cardiac progenitor cells (hCPCs) in vitro. Histological and quantitative analyses of the dermal matrix provided evidence of both effective decellularization with preserved tissue architecture and retention of ECM proteins and growth factors typical of cardiac matrix. Further, the elastic modulus of the dermal matrix resulted comparable with that reported in literature for the human myocardium and, when tested in vitro, dermal matrix resulted a comfortable and protective substrate promoting and supporting hCPC engraftment, survival and cardiomyogenic potential. Our study provides compelling evidence that dermal matrix holds promise as a fully autologous and cost-effective biological scaffold for CTE.
Highlights
Accounting for more than 13% of all deaths, ischemic heart disease (IHD) is the single most common cause of death globally (GBD 2016 Causes of Death Collaborators, 2017)
Following the simple and effective protocol we recently described for the decellularization of human myocardial sections (Di Meglio et al, 2017), skin specimens and 600-μm-thick sections of human myocardium were incubated in decellularizing solution for 24 h
D-HuSk fulfilled the requirements proposed for the evaluation of the effectiveness of decellularization procedures, which include the absence of nuclei as revealed by histology and a content of dsDNA per mg of dry tissue below the set threshold of 50 ng (Crapo et al, 2011)
Summary
Accounting for more than 13% of all deaths, ischemic heart disease (IHD) is the single most common cause of death globally (GBD 2016 Causes of Death Collaborators, 2017). While in the native myocardium elasticity is essentially conferred by the cardiomyocytes themselves (Jacot et al, 2010) and, the decellularization process leads to scaffolds with poor mechanical properties, skin elasticity is provided by the ECM rather than by the resident cells and, the decellularization treatment is unlikely to cause loss of elasticity (Hoganson et al, 2010; Krieg and Aumailley, 2011) On this basis, we hypothesize that dermal decellularized ECM (d-ECM) may represent an innovative and viable alternate biological scaffold to restore myocardial microenvironment for future in vitro cardiac tissue production. 600-μm-thick sections of d-HuSk were seeded with resident human cardiac progenitor cells (hCPCs) to test their ability to ensure hCPC engraftment and survival and to support hCPC retention of the expression of markers specific for cardiac myocytes
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
