cell-patterning-using-magnetic-archimedes-strategy

Cell Patterning Using Magnetic-Archimedes Strategy

Cell patterning, allowing precise control of cell positioning, presents a unique advantage in the study of cell behavior. In this protocol, a cell ...

Zhejiang University School of Medicine

State Key Laboratory of Transvascular Implantation Devices

Cardiovascular Key Laboratory of Zhejiang Province

As the most important component of the vascular wall, vascular smooth muscle cells (VSMCs) participate in the pathological process by phenotype transformation or differentiation from stem/progenitor cells. The main purpose of this study was to reveal the role and related molecular mechanism of microRNA-30c-5p (miR-30c-5p) in VSMC differentiation from adventitial progenitor cells expressing stem cell antigen-1(Sca-1).

MiR-30c-5p regulates adventitial progenitor cells differentiation to vascular smooth muscle cells through targeting OPG.

Perivascular tissue including adipose layer and adventitia have been considered to play pivotal roles in vascular development and disease progression. Recent studies showed that abundant stem/progenitorcells (SPCs) are present in perivascular tissues. These SPCs exhibit capability to proliferate and differentiate into specific terminal cells. Adult perivascular SPCs are quiescent in normal condition, once activated by specific molecules (e.g., cytokines), they migrate toward the lumen side where they differentiate into both smooth muscle cells (SMCs) and endothelial cells (ECs), thus promoting intima hyperplasia or endothelial regeneration. In addition, perivascular SPCs can also regulate vascular diseases via other ways including but not limited to paracrine effects, matrix protein modulation and microvessel formation. Perivascular SPCs have also been shown to possess therapeutic potentials due to the capability to differentiate into vascular cells and regenerate vascular structures. This review summarizes current knowledge on resident SPCs features and discusses the potential benefits of SPCs therapy in vascular diseases.

Perivascular tissue stem cells are crucial players in vascular disease.

CD34 cells are believed being progenitors that may be used to treat cardiovascular disease. However, the exact identity and the role of CD34 cells in physiological and pathological conditions remain unclear.

CD34 cell atlas of main organs implicates its impact on fibrosis.

Tissue engineering raised a high requirement to control cell distribution in defined materials and structures. In "ink"-based bioprintings, such as 3D printing and photolithography, cells were associated with inks for spatial orientation; the conditions suitable for one ink are hard to apply on other inks, which increases the obstacle in their universalization. The Magneto-Archimedes effect based (Mag-Arch) strategy can modulate cell locomotion directly without impelling inks. In a paramagnetic medium, cells were repelled from high magnetic strength zones due to their innate diamagnetism, which is independent of substrate properties. However, Mag-Arch has not been developed into a powerful bioprinting strategy as its precision, complexity, and throughput are limited by magnetic field distribution. By controlling the paramagnetic reagent concentration in the medium and the gaps between magnets, which decide the cell repelling scope of magnets, we created simultaneously more than a hundred micrometer scale identical assemblies into designed patterns (such as alphabets) with single/multiple cell types. Cell patterning models for cell migration and immune cell adhesion studies were conveniently created by Mag-Arch. As a proof of concept, we patterned a tumor/endothelial coculture model within a covered microfluidic channel to mimic epithelial-mesenchymal transition (EMT) under shear stress in a cancer pathological environment, which gave a potential solution to pattern multiple cell types in a confined space without any premodification. Overall, our Mag-Arch patterning presents an alternative strategy for the biofabrication and biohybrid assembly of cells with biomaterials featured in controlled distribution and organization, which can be broadly employed in tissue engineering, regenerative medicine, and cell biology research.

Programing Cell Assembly via Ink-Free, Label-Free Magneto-Archimedes Based Strategy.

Single-nanoparticle detection has received tremendous interest due to its significance in fundamental physics and biological applications. Here, we demonstrate an optical nanofibre-enabled microfluidic sensor for the detection and sizing of nanoparticles. Benefitting from the strong evanescent field outside the nanofibre, a nanoparticle close to the nanofibre can scatter a portion of the field energy to the environment, resulting in a decrease in the transmitted intensity of the nanofibre. On the other hand, the narrow and shallow microfluidic channel provides a femtoliter-scale detection region, making nanoparticles flow through the detection region one by one. By real-time monitoring of the transmitted intensity of the nanofibre, the detection of a single polystyrene (PS) nanoparticle as small as 100 nm in diameter and exosomes in solution is realised. Based on a statistical analysis, the mean scattering signal is related to the size of the nanoparticle. Experimentally, a mixture of nanoparticles of different diameters (200, 500, and 1000 nm) in solution is identified. To demonstrate its potential in biological applications, high-throughput counting of yeasts using a pair of microchannels and dual-wavelength detection of fluorescently labelled nanoparticles are realised. We believe that the developed nanoparticle sensor holds great potential for the multiplexed and rapid sensing of diverse viruses.

An optical nanofibre-enabled on-chip single-nanoparticle sensor.

Calcific aortic valve disease is a prevalent cardiovascular disease with no available drugs capable of effectively preventing its progression. Hence, an efficient drug delivery system could serve as a valuable tool in drug screening and potentially enhance therapeutic efficacy. However, due to the rapid blood flow rate associated with aortic valve stenosis and the lack of specific markers, achieving targeted drug delivery for calcific aortic valve disease has proved to be challenging. Here we find that protease-activated-receptor 2 (PAR2) expression is up-regulated on the plasma membrane of osteogenically differentiated valvular interstitial cells. Accordingly, we develop a magnetic nanocarrier functionalized with PAR2-targeting hexapeptide for dual-active targeting drug delivery. We show that the nanocarriers effectively deliver XCT790-an anti-calcification drug-to the calcified aortic valve under extra magnetic field navigation. We demonstrate that the nano-cargoes consequently inhibit the osteogenic differentiation of valvular interstitial cells, and alleviate aortic valve calcification and stenosis in a high-fat diet-fed low-density lipoprotein receptor-deficient (Ldlr) mouse model. This work combining PAR2- and magnetic-targeting presents an effective targeted drug delivery system for treating calcific aortic valve disease in a murine model, promising future clinical translation.

Article	Year
MiR-30c-5p regulates adventitial progenitor cells differentiation to vascular smooth muscle cells through targeting OPG. Stem cell research & therapy\| PubMed ID: 33468212	2021
Perivascular tissue stem cells are crucial players in vascular disease. Free radical biology & medicine\| PubMed ID: 33556462	2021
CD34 cell atlas of main organs implicates its impact on fibrosis. Cellular and molecular life sciences : CMLS\| PubMed ID: 36315271	2022
Programing Cell Assembly via Ink-Free, Label-Free Magneto-Archimedes Based Strategy. ACS nano\| PubMed ID: 37363813	2023
An optical nanofibre-enabled on-chip single-nanoparticle sensor. Lab on a chip\| PubMed ID: 37874569	2023
Enhancing aortic valve drug delivery with PAR2-targeting magnetic nano-cargoes for calcification alleviation. Nature communications\| PubMed ID: 38228638	2024

Xuhao Zhou

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