Vascular differentiation of bone marrow stem cells is directed by a tunable three-dimensional matrix

Zhang, Ge; Drinnan, Charles T.; Geuss, Laura R.; Suggs, Laura J.

doi:10.1016/j.actbio.2010.03.019

Cited by 76 publications

(79 citation statements)

References 34 publications

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“…Fibrin, PEGylated in different molar ratios, was used for encapsulation of HUVECs and hASCs in order to evaluate the optimal gel compositions for cell growth, including the ratio of thrombin and fibrinogen. Based on previous scientific reports, we have chosen 10:1 and 5:1 PEGylation ratios for fibrinogen modification [14,25]. In contrast to pure fibrin, PEGylated fibrin gels remained fully transparent upon crosslinking with thrombin, which represents a physico-optical benefit and enables deep microscopic analysis of cells cultured within the fibrin hydrogel.…”

Section: Discussionmentioning

confidence: 99%

“…Several publications have reported on entrapment of living cells within 3-D PEG modified fibrin matrices for studying cell migration, proliferation, differentiation, and tubulogenesis [13][14][15][16]. Zhang et al have reported on the development of a 3-D PEGylated fibrin matrix with tunable physical and mechanical properties [15].…”

Section: Introductionmentioning

confidence: 99%

“…Zhang et al have reported on the development of a 3-D PEGylated fibrin matrix with tunable physical and mechanical properties [15]. The effects of various formulations of PEGylated fibrin environments on the differentiation of human mesenchymal stem cells (hMSCs) towards a vascular phenotype were investigated by analysis of angiogenic gene expression and phenotypic immunofluorescent staining.…”

Section: Introductionmentioning

confidence: 99%

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Hydrogel-based microfluidics for vascular tissue engineering

Koroleva

Deiwick

Nguyen³

et al. 2016

BioNanoMaterials

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Abstract:In this work, we have explored 3-D co-culture of vasculogenic cells within a synthetically modified fibrin hydrogel. Fibrinogen was covalently linked with PEG-NHS in order to improve its degradability resistance and physico-optical properties. We have studied influences of the degree of protein PEGylation and the concentration of enzyme thrombin used for the gel preparation on cellular responses. Scanning electron microscopy analysis of prepared gels revealed that the degree of PEGylation and the concentration of thrombin strongly influenced microstructural characteristics of the protein hydrogel. Human umbilical vein endothelial cells (HUVECs) and human adipose-derived stem cells (hASCs), used as vasculogenic co-culture, could grow in 5:1 PEGylated fibrin gels prepared using 1:0.2 protein to thrombin ratio. This gel formulation supported hASCs and HUVECs spreading and the formation of cell extensions and cell-to-cell contacts. Expression of specific ECM proteins and vasculogenic process inherent cellular enzymatic activity were investigated by immunofluorescent staining, gelatin zymography, western blot and RT-PCR analysis. After evaluation of the optimal gel composition and PEGylation ratio, the hydrogel was utilized for investigation of vascular tube formation within a perfusable microfluidic system. The morphological development of this co-culture within a perfused hydrogel over 12 days led to the formation of interconnected HUVEC-hASC network. The demonstrated PEGylated fibrin microfluidic approach can be used for incorporating other cell types, thus representing a unique experimental platform for basic vascular tissue engineering and drug screening applications.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hydrogel-based microfluidics for vascular tissue engineering

Koroleva

Deiwick

Nguyen³

et al. 2016

BioNanoMaterials

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“…As cells migrate away from their CSM base and enter their surrounding extracellular environment, the cells take cue from the scaffold and can either maintain "stemness" (collagen) or be induced to differentiate toward vascular-and vascular-supportive cell types (fibrin). Since our lab is interested in skin and soft-tissue wound healing, we strategically implemented a bilayer of collagen and fibrin since collagen supports dermal and epidermal regeneration by the host, whereas fibrin naturally induces vascular network formation 9 . Furthermore, it is now understood that cross-talk occurs between proliferating skin keratinocytes, fibroblast, and the underlying vascular network; and this complex mechanism is highly critical for proper wound healing 10 .…”

Section: Discussionmentioning

confidence: 99%

Engineering a Bilayered Hydrogel to Control ASC differentiation

Natesan

Zamora

Suggs

et al. 2012

JoVE

Self Cite

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Natural polymers over the years have gained more importance because of their host biocompatibility and ability to interact with cells in vitro and in vivo. An area of research that holds promise in regenerative medicine is the combinatorial use of novel biomaterials and stem cells. A fundamental strategy in the field of tissue engineering is the use of three-dimensional scaffold (e.g., decellularized extracellular matrix, hydrogels, micro/nano particles) for directing cell function. This technology has evolved from the discovery that cells need a substrate upon which they can adhere, proliferate, and express their differentiated cellular phenotype and function 2-3 . More recently, it has also been determined that cells not only use these substrates for adherence, but also interact and take cues from the matrix substrate (e.g., extracellular matrix, ECM) 4 . Therefore, the cells and scaffolds have a reciprocal connection that serves to control tissue development, organization, and ultimate function. Adipose-derived stem cells (ASCs) are mesenchymal, non-hematopoetic stem cells present in adipose tissue that can exhibit multi-lineage differentiation and serve as a readily available source of cells (i.e. pre-vascular endothelia and pericytes). Our hypothesis is that adipose-derived stem cells can be directed toward differing phenotypes simultaneously by simply co-culturing them in bilayered matrices 1 . Our laboratory is focused on dermal wound healing. To this end, we created a single composite matrix from the natural biomaterials, fibrin, collagen, and chitosan that can mimic the characteristics and functions of a dermal-specific wound healing ECM environment. Video LinkThe video component of this article can be found at http://www.jove.com/video/3953/ Protocol 1. Isolating Adipose-Derived Stem Cells (ASCs) 1, 5 Note: All procedures were performed at room temperature unless otherwise noted.

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“…5 Furthermore, it could direct endothelial differentiation of endothelial progenitor cells or marrow stem cells. 6,7 Moreover, the ECM has been used frequently to load growth factors and cytokines, preventing them from degradation and inactivation. 8,9 The present ECM modification of CVIs aims to mimic the microenvironment of ECs, namely the basement membrane.…”

Section: Introductionmentioning

confidence: 99%

Effect of Tissue Specificity on the Performance of Extracellular Matrix in Improving Endothelialization of Cardiovascular Implants

Yang

Zhu

et al. 2013

Tissue Engineering Part A

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Natural extracellular matrix (ECM) deposited in situ by cultured endothelial cells (ECs) has been proven effective in accelerating endothelialization of titanium (Ti) cardiovascular implants (CVIs) in our previous studies. In this study, the ECM deposited by smooth muscle cells (SMCs) was used in comparison to investigate the effects of tissue specificity of the ECM on the ability to accelerate endothelialization of CVIs. The results demonstrated that the ECM deposited by ECs and SMCs (EC-ECM, SMC-ECM, respectively) differed considerably in components and fibril morphology. Surface modification of Ti CVIs with both types of natural ECM was effective in improving their in vitro hemocompatibility and cytocompatibility simultaneously. However, the endothelialization of ECM-modified Ti CVIs in a canine model demonstrated a high tissue specificity of the ECM. Although the ECM deposited by SMCs (SMC-ECM) induced fewer platelet adhesion and sustained better growth and viability of ECs in vitro, its performance in accelerating in vivo endothelialization of Ti CVIs was extremely poor. In contrast, the ECM deposited by ECs (EC-ECM) led to complete endothelium formation in vivo.

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Vascular differentiation of bone marrow stem cells is directed by a tunable three-dimensional matrix

Cited by 76 publications

References 34 publications

Hydrogel-based microfluidics for vascular tissue engineering

Hydrogel-based microfluidics for vascular tissue engineering

Engineering a Bilayered Hydrogel to Control ASC differentiation

Effect of Tissue Specificity on the Performance of Extracellular Matrix in Improving Endothelialization of Cardiovascular Implants

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