Cardiac patches made of brown adipose-derived stem cell sheets and conductive electrospun nanofibers restore infarcted heart for ischemic myocardial infarction

Cell sheet engineering has been proven to be a promising strategy for cardiac remodeling post-myocardial infarction. However, insufficient mechanical strength and low cell retention lead to limited therapeutic efficiency. The thickness and area of artificial cardiac patches also affect their therapeutic efficiency. Cardiac patches prepared by combining cell sheets with electrospun nanofibers, which can be transplanted and sutured to the surface of the infarcted heart, promise to solve this problem. Here, we fabricated a novel cardiac patch by stacking brown adipose-derived stem cells (BADSCs) sheet layer by layer, and then they were combined with multi-walled carbon nanotubes (CNTs)-containing electrospun polycaprolactone/silk fibroin nanofibers (CPSN). The results demonstrated that BADSCs tended to generate myocardium-like structures seeded on CPSN. Compared with BADSCs suspension-containing electrospun nanofibers, the transplantation of the CPSN-BADSCs sheets (CNBS) cardiac patches exhibited accelerated angiogenesis and decreased inflammation in a rat myocardial infarction model. In addition, the CNBS cardiac patches could regulate macrophage polarization and promote gap junction remodeling, thus restoring cardiac functions. Overall, the hybrid cardiac patches made of electrospun nanofibers and cell sheets provide a novel solution to cardiac remodeling after ischemic myocardial infarction.

Embryoid bodies formation and differentiation from mouse embryonic stem cells in collagen/Matrigel scaffolds

Embryonic stem （ES） cells have the potential to develop into any type of tissue and are considered as a promising source of seeding cells for tissue engineering and transplantation therapy.The main catalyst for ES cells differentiation is the growth into embryoid bodies （EBs）,which are utilized widely as the trigger of in vitro differentiation.In this study,a novel method for generating EBs from mouse ES cells through culture in collagen/Matrigel scaffolds was successfully established.When single ES cells were seeded in three dimensional collagen/Matrigel scaffolds,they grew into aggregates gradually and formed simple EBs with circular structures.After 7 days＇ culture,they formed into cystic EBs that would eventually differentiate into the three embryonic germ layers.Evaluation of the EBs in terms of morphology and potential to differentiate indicated that they were typical in structure and could generate various cell types;they were also able to form into tissue-like structures.Moreover,with introduction of ascorbic acid,ES cells differentiated into cardiomyocytes efficiently and started contracting synchronously at day 19.The results demonstrated that collagen/Matrigel scaffolds supported EBs formation and their subsequent differentiation in a single three dimensional environment.

Identification and characterization of mammaglobin-A epitope in heterogenous breast cancers for enhancing tumor-targeting therapy

Although targeted therapy has been extensively investigated for breast cancers,a molecular target with broad application is currently unavailable due to the high heterogeneity of these cancers.Mammaglobin-A(Mam-A),which is overexpressed in most breast carcinomas,has been proposed as a promising target.However,the lack of specific targeting moieties due to uncertain binding epitopes hampers further translational study.Here,seven potential epitopes of Mam-A were disclosed,and a unique epitope was then identified in most types of breast cancers,despite the genotypic heterogeneity.With phage display technology,the epitope was determined to be N-terminal amino acids 42–51 of Mam-A(N42–51).Then,the N42–51 epitope-specific monoclonal antibody,mAb785,was conjugated to poly lactic-co-glycolic acid(PLGA)nanoparticles loaded with therapeutic agents,thereby enhancing the drug uptake and therapeutic efficacy in different genotypes of breast cancers.The computer simulation of the N42–51 epitope and the mAb785 structures,as well as their interactions,further revealed the specific targeting mechanism of the mAb785-conjugated nanoparticles to breast cancers.