Cell-derived extracellular matrix-coated silk fibroin scaffold for cardiogenesis of brown adipose stem cells through modulation of TGF-β pathway

Abstract

The cell-derived extracellular matrix (ECM)-modified scaffolds have advantages of mimic tissue specificity and been thought to better mimic the native cellular microenvironment in vitro. ECM derived from cardiac fibroblasts (CFs) are considered as key elements that provide a natural cell growth microenvironment and change the fate of cardiomyocytes (CMs). Here, a new hybrid scaffold is designed based on silk fibroin (SF) scaffold and CFs-derived ECM. CFs were seeded on the SF scaffold for 10 days culturing and decellularized to produce CFs-derived ECM-coated SF scaffold. The results showed that the cell-derived ECM-modified silk fibroin scaffold material contained collagen, laminin, fibronectin and other ECM components with myocardial-like properties. Further to explore its effects on brown adipose stem cells (BASCs) differentiation into CMs. We found that the CF-derived ECM-coated scaffold also increased the expression of CM-specific proteins (e.g. cardiac troponin T and α-actinin) of BASCs. Notably, the β1-integrin-dependent transforming growth factor-β1 signaling pathway was also involved in the regulation of CF-derived ECM by promoting the differentiation of BASCs into CMs. Overall, these findings provide insights into the bionic manufacturing of engineered cardiac tissues (ECTs) and establish a theoretical basis for the construction of ECTs.

Application potential of three-dimensional silk fibroin scaffold using mesenchymal stem cells for cardiac regeneration

“…26,32 The potential usage of 3D SF scaffold to support cell attachment and proliferation was confirmed by the quantitative and qualitative cell viability assays as required by ISO 10993-5 guidelines. These findings were confirmed with the studies in which the usage of SF alone, 21 and its modified versions; ECM coated-SF, 20 hyaluronic acid/SF-PLC, 15 and SF-PLC, 16 scaffolds were also significantly induced cell viability and proliferation of rat BMSCs, hAD-MSCs, 20,21 and hBMSCs, 15,16 for various tissue engineering applications, respectively. Although, hAD-MSCs with SF scaffold was used for bone regeneration, the application of hAD-MSC as an alternative cell source on 3D SF scaffolds was only used for cardiac tissue engineering in our study.…”

“…18 Another approach was the modification of SF with decellularized extracellular matrix (ECM) to improve cell attachment and migration. 19,20 Different production strategies have been used to produce scaffolds in the form of nanofiber mats, 12,17 patches, 14 patterned films, 12,18 and sponges. 10,11 In several studies, SF was used as coating material to improve cell behavior on the surface.…”

“…10,11 In several studies, SF was used as coating material to improve cell behavior on the surface. 13,15,16 The potential usage of SF-based scaffolds in cardiac tissue engineering has been shown both in vitro and in vivo systems using isolated rat cardiac cells, 10,12,13,19 mice/rat AD-MSCs, 13,20 and rat bone marrow (BM) MSCs, 14 The majority of these applications especially in vivo studies involved the usage of cells derived from rodents. Although SF scaffolds have been used with the cells isolated from human such as human BMSCs, 15,16 human menstrual blood SCs, 11 and human embryonic SC (hESCs) 18 for cardiac studies,there has been no report on the usage of hAD-MSCs with SF scaffolds for cardiac regeneration/repair studies.…”

Segmentally Demineralized Cortical Bone With Stem Cell-Derived Matrix Promotes Proliferation, Migration and Differentiation of Stem Cells in vitro

“…However, we found that H 2 O 2 removes some biochemical components of DCB, such as vascular endothelial growth factor and TGF-β1, inducing chondrogenic or tenogenic differentiation of stem cells. Stem cell-derived ECM could provide a special microenvironment to promote the healing of injured tissues (Yang et al, 2018b;Carvalho et al, 2019;Liu et al, 2020). Therefore, we used TDSC-derived ECM to modify the sDCB-D region of sDCB for improving the chondrogenic or tenogenic differentiation of stem cells.…”

A Robustly Supported Extracellular Matrix Improves the Intravascular Delivery Efficacy of Endothelial Progenitor Cells

“…Moreover, the existing substrate pre‐treatments and crosslinking methods can cause the ECM detachment from substrates and structural and chemical variations in ECMs. [ 15,16 ]…”