construction-multilayered-mesenchymal-stem-cell-sheet-with-3d-dynamic

Construction of a Multilayered Mesenchymal Stem Cell Sheet with a 3D Dynamic Culture System

Stem cell therapy shows a promising future in regenerating injured organ and tissues, and the cell sheet technique has been developed to improve the low ...

jinan university

Endotoxins including lipopolysaccharide (LPS) could cause endotoxemia which often results in excessive inflammation, organ dysfunction, sepsis, disseminated intravascular coagulation (DIC) or even death. Previously, a novel fibrinogenase (FII) showed protective effects on LPS-induced DIC via activating protein C and suppressing inflammatory cytokines.

A novel fibrinogenase from Agkistrodon acutus venom protects against LPS-induced endotoxemia via regulating NF-κB pathway.

Corticosteroids are efficient anti-inflammation treatments. However, there are still arguments on whether it should be used in keratitis. This study was to observe the effect of corticosteroids on keratocytes both in normal condition and inflammation status in vitro.

Corticosteroids effects on LPS-induced rat inflammatory keratocyte cell model.

Cell sheet techniques offer a promising future for myocardial infarction (MI) therapy; however, insufficient nutrition supply remains the major limitation in maintaining stem cell bioactivity in vitro. In order to enhance cell sheet mechanical strength and bioactivity, a decellularized porcine pericardium (DPP) scaffold was prepared by the phospholipase A2 method, and aspartic acid was used as a spacer arm to improve the vascular endothelial growth factor crosslink efficiency on the DPP scaffold. Based on this scaffold, multilayered bone marrow mesenchymal stem cell sheets were rapidly constructed, using RAD16-I peptide hydrogel as a temporary 3D scaffold, and cell sheets were cultured in either the 3D-dynamic system (DCcs) or the traditional static condition (SCcs). The multilayered structure, stem cell bioactivity, and ultrastructure of DCcs and SCcs were assessed. The DCcs exhibited lower apoptosis, lower differentiation, and an improved paracrine effect after a 48 h culture in vitro compared to the SCcs. Four groups were set to evaluate the cell sheet effect in rat MI model: sham group, MI control group, DCcs group, and SCcs group. The DCcs group improved cardiac function and decreased the infarcted area compared to the MI control group, while no significant improvements were observed in the SCcs group. Improved cell survival, angiogenesis, and Sca-1 cell and c-kit cell amounts were observed in the DCcs group. In conclusion, the DCcs maintained higher stem cell bioactivity by using the 3D-dynamic system to provide sufficient nutrition, and transplanting DCcs significantly improved the cardiac function and angiogenesis.

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

Cardiospheres (CSps) are a promising new form of cardiac stem cells with advantage over other stem cells for myocardial regeneration, but direct implantation of CSps by conventional routes has been limited due to potential embolism. We have implanted CSps into the pericardial cavity and systematically demonstrated its efficacy regarding myocardial infarction. Stem cell potency and cell viability can be optimized in vitro prior to implantation by pre-conditioning CSps with pericardial fluid and hydrogel packing. Transplantation of optimized CSps into the pericardial cavity improved cardiac function and alleviated myocardial fibrosis, increased myocardial cell survival and promoted angiogenesis. Mechanistically, CSps are able to directly differentiate into cardiomyocytes in vivo and promote regeneration of myocardial cells and blood vessels through a paracrine effect with released growth factors as potential paracrine mediators. These findings establish a new strategy for therapeutic myocardial regeneration to treat myocardial infarction.

Article	Year
A novel fibrinogenase from Agkistrodon acutus venom protects against LPS-induced endotoxemia via regulating NF-κB pathway. Immunopharmacology and immunotoxicology\| PubMed ID: 26369367	2015
Corticosteroids effects on LPS-induced rat inflammatory keratocyte cell model. PloS one\| PubMed ID: 28448563	2017
Preparation of high bioactivity multilayered bone-marrow mesenchymal stem cell sheets for myocardial infarction using a 3D-dynamic system. Acta biomaterialia\| PubMed ID: 29627677	2018
Pericardial application as a new route for implanting stem-cell cardiospheres to treat myocardial infarction. The Journal of physiology\| PubMed ID: 29736937	2018

Yingwei Wang

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