Engineered extracellular microenvironment with a tunable mechanical property for controlling cell behavior and cardiomyogenic fate of cardiac stem cells

Choi, Min Yeong; Kim, Jongtae; Lee, Won-Jin; Lee, Yunki; Park, Kyung Min; Yang, Young‐Il; Парк, Ки Донг

doi:10.1016/j.actbio.2017.01.002

Cited by 25 publications

(12 citation statements)

References 54 publications

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“…By growing precardiac embryonic stem cells on HA-hydrogels with elastic moduli ranging from 1 to 10 kPa, a 60% increase in myofibril orientation and a 3-fold increase in Troponin T expression was observed compared to cells grown on mechanically static polyacrylamide hydrogels [ 192 ]. A recent example of modulating the ECM stiffness is shown by Choi et al, where a sol-to-gel transitional gelatin-PEG-tyramine (GPT) hydrogel with tunable mechanical properties was developed [ 193 ]. Hydrogels with elastic moduli of 1.8, 2.8, 5.8, and 8.1 kPa were created by varying the H 2 O 2 concentration.…”

Section: The Cpc Microenvironmentmentioning

confidence: 99%

Cardiac Progenitor Cells and the Interplay with Their Microenvironment

Mauretti

Spaans

Bax

et al. 2017

Stem Cells International

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The microenvironment plays a crucial role in the behavior of stem and progenitor cells. In the heart, cardiac progenitor cells (CPCs) reside in specific niches, characterized by key components that are altered in response to a myocardial infarction. To date, there is a lack of knowledge on these niches and on the CPC interplay with the niche components. Insight into these complex interactions and into the influence of microenvironmental factors on CPCs can be used to promote the regenerative potential of these cells. In this review, we discuss cardiac resident progenitor cells and their regenerative potential and provide an overview of the interactions of CPCs with the key elements of their niche. We focus on the interaction between CPCs and supporting cells, extracellular matrix, mechanical stimuli, and soluble factors. Finally, we describe novel approaches to modulate the CPC niche that can represent the next step in recreating an optimal CPC microenvironment and thereby improve their regeneration capacity.

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Section: The Cpc Microenvironmentmentioning

confidence: 99%

Cardiac Progenitor Cells and the Interplay with Their Microenvironment

Mauretti

Spaans

Bax

et al. 2017

Stem Cells International

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“…The reason why hMSCs cultured in GH-7-L gels spread more is likely due to a faster degradation rate of cross-linked gelatin matrix, which leaves more room for cell spreading and nutrient/oxygen transport. In addition, other previous studies also demonstrated that lower cross-linking density resulted in an increase in mesh size, swelling degree, and degradation rate, thus enhanced cellular activities such as cell migration and growth in 3D cell culture system [ 31 , 32 ].…”

Section: Resultsmentioning

confidence: 95%

In Situ Forming Gelatin Hydrogels-Directed Angiogenic Differentiation and Activity of Patient-Derived Human Mesenchymal Stem Cells

Lee

Balikov

Lee

et al. 2017

IJMS

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Directing angiogenic differentiation of mesenchymal stem cells (MSCs) still remains challenging for successful tissue engineering. Without blood vessel formation, stem cell-based approaches are unable to fully regenerate damaged tissues due to limited support for cell viability and desired tissue/organ functionality. Herein, we report in situ cross-linkable gelatin−hydroxyphenyl propionic acid (GH) hydrogels that can induce pro-angiogenic profiles of MSCs via purely material-driven effects. This hydrogel directed endothelial differentiation of mouse and human patient-derived MSCs through integrin-mediated interactions at the cell-material interface, thereby promoting perfusable blood vessel formation in vitro and in vivo. The causative roles of specific integrin types (α1 and αvβ3) in directing endothelial differentiation were verified by blocking the integrin functions with chemical inhibitors. In addition, to verify the material-driven effect is not species-specific, we confirmed in vitro endothelial differentiation and in vivo blood vessel formation of patient-derived human MSCs by this hydrogel. These findings provide new insight into how purely material-driven effects can direct endothelial differentiation of MSCs, thereby promoting vascularization of scaffolds towards tissue engineering and regenerative medicine applications in humans.

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“…A total of 2 × 10 6 in vitro cultured MSCs were mixed with the GH polymer (5 wt%) that containing 0.0015 mg/mL of horseradish peroxidase (HRP). The hydrogel formation was occurred when the solution mixed with same volume of GH polymer (5 wt%) that containing 0.005 wt% hydrogen peroxide (H 2 O 2 ) 60 . At 8 weeks after the operation, the rabbits were euthanized and defect sites were extracted for the histological analysis.…”

Section: Methodsmentioning

confidence: 99%

Enhanced articular cartilage regeneration with SIRT1-activated MSCs using gelatin-based hydrogel

et al. 2018

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To investigate the functional effects of resveratrol (RSV) on mesenchymal stem cells (MSCs), we treated MSCs with RSV continuously during ex vivo expansion. MSCs were continuously treated with RSV from passage (P) 0 to P5. A proliferative capacity of RSV-treated MSCs was higher than that of non-treated MSCs and similar with P1-MSCs. Continuous treatment of RSV on MSCs increased the stemness and inhibited the senescence. During chondrogenic differentiation in vitro, RSV-treated MSCs had higher differentiation potential and reduced hypertrophic maturation, which are limitations for hyaline cartilage formation. The histological analysis of micromass demonstrated increased chondrogenic differentiation potential. We further explored the therapeutic effectiveness of this method in a rabbit osteochondral defect model. A rabbit osteochondral defect model was established to investigate the hyaline cartilage regeneration potential of RSV-treated MSCs. Moreover, the cartilage regeneration potential of RSV-treated MSCs was greater than that of untreated MSCs. The expression levels of chondrogenic markers increased and those of hypertrophic markers decreased in RSV-treated MSCs compared with untreated MSCs. Sustained treatment of RSV on MSCs during ex vivo expansion resulted in the maintenance of stemness and enhanced chondrogenic differentiation potential. Consequentially, highly efficient MSCs promoted superior hyaline cartilage regeneration in vivo. This novel treatment method provides a basis for cell-based tissue engineering.

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Engineered extracellular microenvironment with a tunable mechanical property for controlling cell behavior and cardiomyogenic fate of cardiac stem cells

Cited by 25 publications

References 54 publications

Cardiac Progenitor Cells and the Interplay with Their Microenvironment

Cardiac Progenitor Cells and the Interplay with Their Microenvironment

In Situ Forming Gelatin Hydrogels-Directed Angiogenic Differentiation and Activity of Patient-Derived Human Mesenchymal Stem Cells

Enhanced articular cartilage regeneration with SIRT1-activated MSCs using gelatin-based hydrogel

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