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Search terms: exosomes OR "extracellular vesicles" OR microvesicles OR microparticles. Direct link to the PubMed search here.

Multiplexing Techniques for Measurement of the Immunomodulatory Effects of Particulate Materials: Precautions When Testing Micro- and Nano-particles.

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Multiplexing Techniques for Measurement of the Immunomodulatory Effects of Particulate Materials: Precautions When Testing Micro- and Nano-particles.

Methods. 2019 Jan 17;:

Authors: Elsabahy M, Wooley KL, Hendricksen A, Oh K

Abstract
Particulate materials at nano- and micro-scales have widespread pharmaceutical and medical applications. Understanding the interactions of these materials with biological systems is crucial for the design of clinically-viable biomaterials of high safety profiles. Immunomodulatory effects of particulate materials can be studied via multiplexing techniques that are capable of measuring up to 500 biomarkers in a few microliters of biological samples. However, there are several challenges towards the use of multiplexing techniques for testing the ability of nanomaterials to induce the release of various biomarkers. As one of the potential challenges, the adsorption of biomarkers on surfaces or within internal structures of nano- or micro-particles has been explored to a lesser extent, although it can lead to biased conclusions and data misinterpretation. Herein, we provide technical details on the use of multiplexing techniques for the evaluation of immunomodulatory effects of nanoparticulates. The same principles can also be applied for the assessment of microparticles. Importantly, precautions to avoid artifacts and data misinterpretation, due to interactions between particles and biomarkers, are provided.

PMID: 30660862 [PubMed - as supplied by publisher]

Construction of multicellular aggregate by E-cadherin coated microparticles enhancing the hepatic specific differentiation of mesenchymal stem cells.

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Construction of multicellular aggregate by E-cadherin coated microparticles enhancing the hepatic specific differentiation of mesenchymal stem cells.

Acta Biomater. 2019 Jan 17;:

Authors: Cao L, Zhang Y, Qian M, Wang X, Shuai Q, Gao C, Lang R, Yang J

Abstract
The differentiation of human mesenchymal stem cells (hMSCs) into hepatocyte-like cells in vitroprovides a promising candidate for cell therapy of liver diseases, and cell aggregates have been proposed to improve the efficiency of expansion and differentiation. Previously, we engineered multicellular aggregates incorporating human E-cadherin fusion protein (hE-cad-Fc)-coated poly(lactic-co-glycolic acid) (PLGA) microparticles (hE-cad-PLGAs), and a significant improvement was obtained in both cellular proliferation of and cytokine secretion by hMSCs. In this study, hepatic differentiation of hMSCs was induced by a biomimetic microenvironment consisting of these engineered aggregates and a cocktail of specific cytokines. The ratio of hE-cad-PLGAs to hMSCs in engineered hMSCs aggregates was optimized to 1:3 for hepatic differentiation. The expressions of hepatic-specific markers were significantly promoted, and cell polarity and activated drug metabolism enzymes were established in MSC/hE-cad-PLGA aggregates compared with MSC and MSC/PLGA aggregates. Moreover, the expressions of stemness and definitive endoderm markers confirmed effectively induced endoderm differentiation in MSC/hE-cad-PLGA aggregates, which was consistent with the pattern of embryonic development. After pre-differentiation for 1 week, the MSC/hE-cad-PLGA aggregates continuously progressed the hepatic phenotype expression in healthy rat peritoneum. Therefore, the biomimetic microenvironment constructed by hE-cad-PLGAs in engineered multicellular aggregates was able to promote the process of endoderm differentiation and the subsequent hepatic differentiation of hMSCs. It would be appropriate for applied research in hepatotoxic drug screening and cell-based treatment of liver diseases. By optimizing with other cytokine cocktail, the engineered multicellular aggregates can be applied to the construction of other endoderm-derived organs. STATEMENT OF SIGNIFICANCE: The differentiation of mesenchymal stem cells (MSCs) into hepatocyte-like cells in vitroprovides a promising for cell therapy for liver diseases, and cell aggregates have been proposed to improve the expansion and differentiation efficiency. Here, engineered multicellular aggregates were constructed by E-cadherin modified microparticles (hE-cad-PLGAs) construct a biomimetic microenvironment to promote the process of endoderm differentiation and the subsequent hepatic differentiation of hMSCs. Furthermore, after pre-differentiation for 1 week, the MSC/hE-cad-PLGA aggregates continuously progressed the hepatic phenotype expression in healthy rat peritoneum. Therefore, engineered multicellular aggregates with hE-cad-PLGAs would be appropriate for applied research in hepatotoxic drug screening and cell-based treatment of liver diseases, and provide a promising method in the construction of other endoderm-derived organs.

PMID: 30660779 [PubMed - as supplied by publisher]

 

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