Preparation of high bioactivity multilayered bone-marrow mesenchymal stem cell sheets for myocardial infarction using a 3D-dynamic system

Abstract

This study provides an efficient method to prepare vascular endothelial growth factor covalent decellularized pericardium scaffold with aspartic acid, and a multilayered bone marrow mesenchymal stem cell (BMSC) sheet is constructed on it using a 3D-dynamic system. The dynamic nutrition supply showed a significant benefit on BMSC bioactivity in vitro, including decreasing cell apoptosis, reducing stem cell differentiation, and improving growth factor secretion. These favorable bioactivity improved BMSC survival, angiogenesis, and cardiac function of the infarcted myocardium. The study highlights the importance of dynamic nutrition supply on maintaining stem cell bioactivity within cell sheet, and it stresses the necessity and significance of setting a standard for assessing cell sheet products before transplantation in the future application.

Crosslinked Decellularized Porcine Pericardium as a Substrate for Conjunctival Reconstruction

“…Phospholipase A2 (PLA2) is a kind of hydrolase that acts on ester bonds and completely hydrolyzes triglycerides into fatty acids and glycerol. PLA2 has been proven to be an efficient decellularized method for the preparation of scaffolds [ 21 , 37 ] and has the advantage of maintaining ECM and collagenous structure [ 36 ]. Moreover, the absence of nuclear structures in HE staining was an indicator of effective cell removal during the decellularization process, and the extracellular matrix components type I collagen, type IV collagen, and laminin do not appear to be disrupted following decellularization according to qualitative and quantitative data ( Figure 2 ).…”

“…Meanwhile, chemical crosslinking will significantly inhibit the degradation of biological scaffolds and alter the host tissue response to the biological material [ 16 ]. Asp is a nontoxic, biocompatible, and biodegradable protein widely expressed in the human body and may help to promote damage repair and the production of extracellular matrix [ 21 ]. In this study, Asp was crosslinked with collagen to form hydrogen bonds and was used as a spacer arm to crosslink hEGF on DPP-Asp.…”

“…N-Hydroxysuccinimide (NHS) can enhance the stability of EDC crosslinked products by reacting to generate more stable esters; thus, crosslinking with EDC/NHS can result in a highly aligned fibrillar structure with banding similar to native collagen [ 20 ]. Some reports showed aspartic acid (Asp) crosslinked with epidermal growth factor (EGF) on the scaffold by activating carboxylic acid groups in collagen [ 21 , 22 ].…”

Targeting Programmed Cell Death to Improve Stem Cell Therapy: Implications for Treating Diabetes and Diabetes-Related Diseases

“…Cell culture is conventionally conducted by a two-dimensional (2D) system that often does not adequately replicate the three-dimensional (3D) environment, and it is deficient in cell-to-cell interactions ( Madl et al, 2018 ; Seo et al, 2019 ). The 3D culturing of bone marrow MSCs using a 3D-dynamic system exhibited decreased apoptosis and improved therapeutic effect for cardiac function ( Wang Y. et al, 2018 ). A recently developed 3D culture clump of MSCs/extracellular matrix complexes also showed resistance against apoptosis ( Komatsu et al, 2020 ).…”

Construction of Sandwich-like cell sheets with natural electrospun gelatin/chitosan nanofibrous delivered plasmid VEGF for accelerated wound healing

“…Cell sheet engineering involves many disciplines including medicine, biology, engineering, and pharmacy [2,3], because the noninvasive cell sheet can be engrafted to the desired transplantation site without suturing the cell sheet. Preclinical and Clinical studies have been conducted by cell sheet transplantation for the regeneration of cornea [4], bone [5], tendon [6], myocardium [7] and peridontium [8]. Transplanted cell sheets can replace injured tissue and compensate impaired function when implanted in the ectopic region.…”