An artificial membrane binding protein-polymer surfactant nanocomplex facilitates stem cell adhesion to the cartilage extracellular matrix

Abstract Background Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) are regarded as promising cell type for cardiac cell replacement therapy, but it is not known whether the developmental stage influences their persistence and functional integration in the host tissue, which are crucial for a long-term therapeutic benefit. To investigate this, we first tested the cell adhesion capability of murine iPSC-CM in vitro at three different time points during the differentiation process and then examined cell persistence and quality of electrical integration in the infarcted myocardium in vivo. Methods To test cell adhesion capabilities in vitro, iPSC-CM were seeded on fibronectin-coated cell culture dishes and decellularized ventricular extracellular matrix (ECM) scaffolds. After fixed periods of time, stably attached cells were quantified. For in vivo experiments, murine iPSC-CM expressing enhanced green fluorescent protein was injected into infarcted hearts of adult mice. After 6–7 days, viable ventricular tissue slices were prepared to enable action potential (AP) recordings in transplanted iPSC-CM and surrounding host cardiomyocytes. Afterwards, slices were lysed, and genomic DNA was prepared, which was then used for quantitative real-time PCR to evaluate grafted iPSC-CM count. Results The in vitro results indicated differences in cell adhesion capabilities between day 14, day 16, and day 18 iPSC-CM with day 14 iPSC-CM showing the largest number of attached cells on ECM scaffolds. After intramyocardial injection, day 14 iPSC-CM showed a significant higher cell count compared to day 16 iPSC-CM. AP measurements revealed no significant difference in the quality of electrical integration and only minor differences in AP properties between d14 and d16 iPSC-CM. Conclusion The results of the present study demonstrate that the developmental stage at the time of transplantation is crucial for the persistence of transplanted iPSC-CM. iPSC-CM at day 14 of differentiation showed the highest persistence after transplantation in vivo, which may be explained by a higher capability to adhere to the extracellular matrix.

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Directing Stem Cell Fate in 3D Through Cell Inert and Adhesive Diblock Copolymer Domains

Volume 1B: Extremity; Fluid Mechanics; Gait; Growth, Remodeling, and Repair; Heart Valves; Injury Biomechanics; Mechanotransduction and Sub-Cellular Biophysics; MultiScale Biotransport; Muscle, Tendon and Ligament; Musculoskeletal Devices; Multiscale Mechanics; Thermal Medicine; Ocular Biomechanics; Pediatric Hemodynamics; Pericellular Phenomena; Tissue Mechanics; Biotransport Design and Devices; Spine; Stent Device Hemodynamics; Vascular Solid Mechanics; Student Paper and Design Competitions ◽

10.1115/sbc2013-14442 ◽

2013 ◽

Author(s):

Somyot Chirasatitsin ◽

Priyalakshmi Viswanathan ◽

Giuseppe Battaglia ◽

Adam J. Engler

Keyword(s):

Extracellular Matrix ◽

Stem Cell ◽

Cell Adhesion ◽

Cell Fate ◽

Diblock Copolymer ◽

Stem Cell Differentiation ◽

Stem Cell Fate ◽

Cell Behaviors ◽

Cell Structures

Adhesions are important cell structures required to transduce a variety of chemical and mechanics signals from outside-in and vice versa, all of which regulate cell behaviors, including stem cell differentiation (1). Though most biomaterials are coated with an adhesive ligand to promote adhesion, they do not often have a uniform distribution that does not match the heterogeneously adhesive extracellular matrix (ECM) in vivo (2). We have previously shown that diblock copolymer (DBC) mixtures undergo interface-confined de-mixing to form nanodomins of one copolymer in another (3). Here we demonstrate how diblock copolymer mixtures can be made into foams with nanodomains to better recapitulate native ECM adhesion regions and influence cell adhesion.

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Regulatory effects of stem cell factor and interleukin-4 on adhesion of human mast cells to extracellular matrix proteins

Blood ◽

10.1182/blood.v99.3.966 ◽

2002 ◽

Vol 99 (3) ◽

pp. 966-972 ◽

Cited By ~ 47

Author(s):

Axel Lorentz ◽

Detlef Schuppan ◽

Andreas Gebert ◽

Michael P. Manns ◽

Stephan C. Bischoff

Keyword(s):

Extracellular Matrix ◽

Mast Cell ◽

Stem Cell ◽

Cell Adhesion ◽

Mast Cells ◽

Stem Cell Factor ◽

Collagen I ◽

Interleukin 4 ◽

Human Mast Cells ◽

Ecm Proteins

Abstract Mast cells are inflammatory and immunoregulatory cells resident in tissues. They develop from bone marrow-derived progenitor cells that enter the tissue through the blood circulation. The specific localization and migration of mast cells in tissues is dependent on their interaction with extracellular matrix (ECM) proteins. Adhesion of human mast cells isolated from intestinal mucosa and cultured in the presence of stem cell factor (SCF) to ECM proteins is analyzed. It was observed that SCF is a unique cytokine enhancing mast cell adhesion to all tested ECM proteins (fibronectin, laminin, collagen I, III, IV, VI, XIV) up to 5-fold, particularly to fibronectin (54% ± 12% of mast cells) and to denatured collagens (40% ± 12% on cyanogen bromide-cleaved peptides of collagen I). Most noteworthy, preculture of mast cells with interleukin-4 (IL-4), in addition to SCF, reduced their potency to adhere to ECM proteins to one third compared to mast cells cultured with SCF alone. Mast cell adhesion was preferentially mediated by β1 integrins, and most cells expressed the ECM-binding integrins α2β1, α3β1, α4β1, α5β1, and αVβ3. SCF-induced mast cell adhesion was totally blocked by wortmannin and apigenin, indicating an involvement of phosphatidylinositol 3-kinase and mitogen-activated protein kinase, and it was related to an up-regulation of the HUTS-21 β1 epitope, which is associated with an activated conformation of β1. In conclusion, these data indicate that SCF induces the adhesion of cultured mast cells to ECM proteins, whereas IL-4 may promote detachment from the ECM.

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Stem cell factor modulates avidity of alpha 4 beta 1 and alpha 5 beta 1 integrins expressed on hematopoietic cell lines

Blood ◽

10.1182/blood.v85.1.159.bloodjournal851159 ◽

1995 ◽

Vol 85 (1) ◽

pp. 159-167 ◽

Cited By ~ 137

Author(s):

NL Kovach ◽

N Lin ◽

T Yednock ◽

JM Harlan ◽

VC Broudy

Keyword(s):

Flow Cytometry ◽

Extracellular Matrix ◽

Stem Cell ◽

Cell Adhesion ◽

Stromal Cells ◽

Stem Cell Factor ◽

Hematopoietic Cells ◽

Hematopoietic Cell ◽

Dependent Manner ◽

Prolonged Incubation

Interactions between hematopoietic cells and bone marrow (BM) stroma, composed of extracellular matrix and stromal cells, are crucial for hematopoiesis. Integrins facilitate these interactions by mediating adherence of hematopoiesis. Integrins facilitate these interactions by mediating adherence of hematopoietic cells to both the extracellular matrix and stromal cells. Marrow stromal cells secrete a variety of growth factors, including stem cell factor (SCF). Because treatment with SCF in vivo mobilizes primitive hematopoietic cells from the BM, we investigated the effect of the growth factor SCF of hematopoietic cell adhesion. These studies show that SCF modulates adhesive function in a dose- and time-dependent manner, but does not modulate expression of the integrins alpha 4 beta 1 and alpha 5 beta 1 in the SCF- responsive cell line MO7E. Treatment of MO7E cells with SCF (200 ng/mL) produced a transient increase in adherence to cytokine-activated human umbilical vein endothelial cells (HUVECs) or to vascular cell adhesion molecule 1 (VCAM-1)-transfected Chinese hamster ovary (CHO) cells with peak adhesion at 30 minutes and return to baseline by 60 to 90 minutes. This increase in adhesion was paralleled by increased binding of the beta 1 activation-dependent monoclonal antibody (MoAb) 15/7, as determined by flow cytometry. However, prolonged incubation of MO7E with SCF induced a marked decrease in integrin-mediated adherence, with maximal inhibition by 24 hours. No change in expression of integrins, as determined by flow cytometry, was observed with short- or long-term incubation with SCF. SCF-treated cells were still able to respond to phorbol esters and to the activating beta 1 MoAb 8A2 with increased adherence, but not to the level seen in control cells. This suggests that a subpopulation of expressed alpha 4 beta 1 and alpha 5 beta 1 integrins is disengaged by prolonged incubation with SCF.

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Repair of articular cartilage defect using adipose‐derived stem cell‐loaded scaffold derived from native cartilage extracellular matrix

Journal of Cellular Physiology ◽

10.1002/jcp.30020 ◽

2021 ◽

Author(s):

Liang Lu ◽

Xifu Shang ◽

Bin Liu ◽

Weijian Chen ◽

Yu Zhang ◽

...

Keyword(s):

Extracellular Matrix ◽

Stem Cell ◽

Articular Cartilage ◽

Cartilage Defect ◽

Articular Cartilage Defect ◽

Native Cartilage ◽

Cartilage Extracellular Matrix ◽

Adipose Derived Stem Cell

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Hyaluronan-Based Grafting Strategies for Liver Stem Cell Therapy and Tracking Methods

Stem Cells International ◽

10.1155/2019/3620546 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 3

Author(s):

Lorenzo Nevi ◽

Samira Safarikia ◽

Sabina Di Matteo ◽

Francesca Biancaniello ◽

Michele Francesco Chiappetta ◽

...

Keyword(s):

Extracellular Matrix ◽

Stem Cell ◽

Cell Adhesion ◽

Cell Therapy ◽

Surface Glycoprotein ◽

Target Tissue ◽

Cell Surface Glycoprotein ◽

Cell Functions ◽

Cell Engraftment ◽

Cell Grafting

Cell adhesion is essential for survival, it plays important roles in physiological cell functions, and it is an innovative target in regenerative medicine. Among the molecular interactions and the pathways triggered during cell adhesion, the binding of cluster of differentiation 44 (CD44), a cell-surface glycoprotein involved in cell-cell interactions, to hyaluronic acid (HA), a major component of the extracellular matrix, is a crucial step. Cell therapy has emerged as a promising treatment for advanced liver diseases; however, so far, it has led to low cell engraftment and limited cell repopulation of the target tissue. Currently, different strategies are under investigation to improve cell grafting in the liver, including the use of organic and inorganic biomatrices that mimic the microenvironment of the extracellular matrix. Hyaluronans, major components of stem cell niches, are attractive candidates for coating stem cells since they improve viability, proliferation, and engraftment in damaged livers. In this review, we will discuss the new strategies that have been adopted to improve cell grafting and track cells after transplantation.

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Hierarchical “As-Electrospun” Self-Assembled Fibrous Scaffolds Deconvolute Impacts of Chemically Defined Extracellular Matrix- and Cell Adhesion-Type Interactions on Stem Cell Haptokinesis

ACS Macro Letters ◽

10.1021/acsmacrolett.7b00834 ◽

2017 ◽

Vol 6 (12) ◽

pp. 1420-1425 ◽

Cited By ~ 3

Author(s):

Sandra Camarero-Espinosa ◽

Ilaria Stefani ◽

Justin Cooper-White

Keyword(s):

Extracellular Matrix ◽

Stem Cell ◽

Cell Adhesion ◽

Fibrous Scaffolds ◽

Self Assembled

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Extracellular Matrix Expression in Human Induced Pluripotent Stem Cell-Derived Optic Vesicles

International Journal of Regenerative Medicine ◽

10.31487/j.rgm.2021.02.01 ◽

2021 ◽

pp. 1-10

Author(s):

Heuy-Ching Wang ◽

Ramesh R. Kaini ◽

Christina L. Rettinger ◽

Heuy-Ching Wang

Keyword(s):

Extracellular Matrix ◽

Stem Cell ◽

Cell Adhesion ◽

Adhesion Molecule ◽

Pluripotent Stem Cell ◽

Critical Role ◽

Induced Pluripotent Stem Cell ◽

Ecm Proteins ◽

Optic Vesicles ◽

Induced Pluripotent

Background: Human tissue/organ development is a complex, highly orchestrated process, regulated in part by the surrounding extracellular matrix (ECM). Every complex tissue, including the retina, has a unique ECM configuration that plays a critical role in cellular differentiation, adhesion, migration, and maturation. Aim: To characterize ECM expression of human induced pluripotent stem cell-derived optic vesicles (iPSC-OVs). Methods: A 3- dimensional (3D) in vitro suspension culture system was used to direct differentiation of human induced pluripotent stem cells (iPSCs) into optic vesicles (OVs). Stepwise differentiation of iPSCs into retinal progenitor cells was confirmed by sequential expression of OTX2, SOX1, SIX6, LHX2, PAX6, and CHX10. Expression of ECM genes in iPSC-derived OVs was analyzed by RT2 ProfilerTM PCR Array, whereas immunofluorescence staining was performed to detect ECM proteins in the OVs. Results: A number of cell adhesion molecules (CAMs) previously reported to be abundantly expressed in iPSCs such as E-cadherin, Intercellular adhesion molecule-1 (ICAM1), Integrin-α L, Integrin-α M, Integrin-α 6 were downregulated while neural and retina specific CAMs including neural cell adhesion molecule 1 (NCAM1), neural plakophilin-related armadillo repeat protein (NPRAP), Integrin-α 1 and Integrin-α 4 were upregulated. Several glycoproteins that have been reported to play key roles during retinogenesis, namely CD44, Tenascin C, Tenascin R, Neurocan, Neuroglycan C, Delta 2 Catenin, Vitronectin, and Reelin were also present. Conclusion: We have identified an array of ECM proteins that were expressed during retinogenesis. Further characterization of these proteins will lead to a better understanding of retinal development.

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