Comparison of Mesenchymal Stem Cell Source Differentiation Toward Human Pediatric Aortic Valve Interstitial Cells within 3D Engineered Matrices

Duan, Bin; Hockaday, Laura A.; Das, Shoshana L.; Xu, Charlie; Butcher, Jonathan T.

doi:10.1089/ten.tec.2014.0589

Cited by 35 publications

(56 citation statements)

References 80 publications

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“…BMSCs and human endothelial cells are potential sources of material for the construction of TEHVs but also can be influenced by high FSS . In this study, we also identified important growth factors for the development of TEHVs, including TGF‐ β , bFGF , VEGF , and PDGF , which were decreased by high FSS. BMSC apoptosis was also increased by high FSS in an intensity‐dependent manner.…”

Section: Discussionmentioning

confidence: 73%

Melatonin reverses flow shear stress‐induced injury in bone marrow mesenchymal stem cells via activation of AMP‐activated protein kinase signaling

Yang

Fan

Deng

et al. 2016

Journal of Pineal Research

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Tissue-engineered heart valves (TEHVs) are a promising treatment for valvular heart disease, although their application is limited by high flow shear stress (FSS). Melatonin has a wide range of physiological functions and is currently under clinical investigation for expanded applications; moreover, extensive protective effects on the cardiovascular system have been reported. In this study, we investigated the protection conferred by melatonin supplementation against FSS-induced injury in bone marrow mesenchymal stem cells (BMSCs) and elucidated the potential mechanism in this process. Melatonin markedly reduced BMSC apoptotic death in a concentration-dependent manner while increasing the levels of transforming growth factor β (TGF-β), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and B-cell lymphoma 2 (Bcl2), and decreasing those of Bcl-2-associated X protein (Bax), p53 upregulated modulator of apoptosis (PUMA), and caspase 3. Notably, melatonin exerted its protective effects by upregulating the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), which promotes acetyl-CoA carboxylase (ACC) phosphorylation. Further molecular experiments revealed that luzindole, a nonselective antagonist of melatonin receptors, blocked the anti-FSS injury (anti-FSSI) effects of melatonin. Inhibition of AMPK by Compound C also counteracted the protective effects of melatonin, suggesting that melatonin reverses FSSI in BMSCs through the AMPK-dependent pathway. Overall, our findings indicate that melatonin contributes to the amelioration of FSS-induced BMSC injury by activating melatonin receptors and AMPK/ACC signaling. Our findings may provide a basis for the design of more effective strategies that promote the use of TEHCs in patients.

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Section: Discussionmentioning

confidence: 73%

Melatonin reverses flow shear stress‐induced injury in bone marrow mesenchymal stem cells via activation of AMP‐activated protein kinase signaling

Yang

Fan

Deng

et al. 2016

Journal of Pineal Research

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“…After the measurements of dry weight, total collagen content was determined using a hydroxyproline assay [55]. The collagen values were calculated assuming 12.5% of collagen is hydroxyproline.…”

Section: Methodsmentioning

confidence: 99%

Living nanofiber yarn-based woven biotextiles for tendon tissue engineering using cell tri-culture and mechanical stimulation

et al. 2017

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Non-woven nanofibrous scaffolds have been developed for tendon graft application by using electrospinning strategies. However, electrospun nanofibrous scaffolds face some obstacles and limitations, including suboptimal scaffold structure, weak tensile and suture-retention strengths, and compact structure for cell infiltration. In this work, a novel nanofibrous, woven biotextile, fabricated based on electrospun nanofiber yarns, was implemented as a tissue engineered tendon scaffold. Based on our modified electrospinning setup, polycaprolactone (PCL) nanofiber yarns were fabricated with reproducible quality, and were further processed into plain-weaving fabrics interlaced with polylactic acid (PLA) multifilaments. Nonwoven nanofibrous PCL meshes with random or aligned fiber structures were generated using typical electrospinning as comparative counterparts. The woven fabrics contained 3D aligned microstructures with significantly larger pore size and obviously enhanced tensile mechanical properties than their nonwoven counterparts. The biological results revealed that cell proliferation and infiltration, along with the expression of tendon-specific genes by human adipose derived mesenchymal stem cells (HADMSC) and human tenocytes (HT), were significantly enhanced on the woven fabrics compared with those on randomly-oriented or aligned nanofiber meshes. Co-cultures of HADMSC with HT or human umbilical vein endothelial cells (HUVEC) on woven fabrics significantly upregulated the functional expression of most tenogenic markers. HADMSC/HT/HUVEC tri-culture on woven fabrics showed the highest upregulation of most tendon-associated markers than all the other mono- and co-culture groups. Furthermore, we conditioned the tri-cultured constructs with dynamic conditioning and demonstrated that dynamic stretch promoted total collagen secretion and tenogenic differentiation. Our nanofiber yarn-based biotextiles have significant potential to be used as engineered scaffolds to synergize the multiple cell interaction and mechanical stimulation for promoting tendon regeneration.

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“…We chose these targets because this thickness of precursor solution approximately corresponds between two and three extrusion printed layers of hydrogel (if using a 0.8 mm diameter printing tip) 28 , and could enable printing of a 3 cm tall hydrogel construct in 100 minutes (a scale useful if fabricating a heart valve conduit) 25 . Additionally, our previous work with a methacrylated gelatin and methacrylated hyaluronic acid photocrosslinking hydrogel prepared with Irgacure photoinitiator, demonstrated greater than 80% live/dead HAVIC and HADMSC viability at 14 and 28 days in culture 13 , and VA086 photoinitiator is reportedly less cytotoxic than Irgacure 9,38 . In the present study we quantified the percentage of live HAVIC, HASSMC, and HADMSC in photo-crosslinking encapsulation conditions in MEGEL/PEGDA hydrogels with Irgacure 2959 and VA086 photoinitiators.…”

Section: Introductionmentioning

confidence: 84%

“…Photoinitiators 2,2′-Azobis[2-methyl-N-(2-hydroxyethyl)propionamide] (VA086, Wako Chemicals) and 2-hydroxy-1(4-(hydroxyethox)pheny)-2-methyl-1-propanone (Irgacure 2959, BASF Corporation, Newport, DE) were dissolved in 70% ethanol and sterile filtered to make stock solutions (0.1g VA086/ml, 0.015g Irgacure/ml) 9,38 . Irgacure photoinitiator was investigated because it has been one of the most widely used in contact with cells 19 and it has been previously used in the photo-encapsulation of both valve and adipose derived stem cells 13,15 . VA086 photoinitiator was investigated because it is reportedly less cytotoxic compared to Irgacure 9,38 .…”

Section: Methodsmentioning

confidence: 99%

“…S1 and Table S1). The lower intensity light sources were tested because we had previously found them effective for photocrosslinking other hydrogel precursor solutions 13,15,25 and we built and tested the high LED array light source so less efficiently crosslinking photoinitiator and polymer precursor combinations could be tested. To test a range, a high and a low light intensity (2 and 136 mW/cm 2) , were selected for mechanical testing and cell encapsulation.…”

Section: Methodsmentioning

confidence: 99%

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Optimizing Photo-Encapsulation Viability of Heart Valve Cell Types in 3D Printable Composite Hydrogels

et al. 2016

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Photocrosslinking hydrogel technologies are attractive for the biofabrication of cardiovascular soft tissues, but 3D printing success is dependent on multiple variables. In this study we systematically test variables associated with photocrosslinking hydrogels (photoinitiator type, photoinitiator concentration, and light intensity) for their effects on encapsulated cells in an extrusion 3D printable mixture of methacrylated gelatin/poly-ethylene glycol diacrylate/alginate (MEGEL/PEGDA3350/alginate). The fabrication conditions that produced desired hydrogel mechanical properties were compared against those that optimize aortic valve or mesenchymal stem cell viability. In the 3D hydrogel culture environment and fabrication setting studied, Irgacure can increase hydrogel stiffness with a lower proportional decrease in encapsulated cell viability compared to VA086. Human adipose derived mesenchymal stem cells (HADMSC) survived increasing photoinitiator concentrations in photo-encapsulation conditions better than aortic valve interstitial cells (HAVIC) and aortic valve sinus smooth muscle cells (HASSMC). Within the range of photo-encapsulation fabrication conditions tested with MEGEL/PEGDA/alginate (0.25–1.0% w/v VA086, 0.025–0.1% w/v Irgacure 2959, and 365 nm light intensity 2–136 mW/cm2), the highest viabilities achieved were 95%, 93%, and 93% live for HASSMC, HAVIC, and HADMSC respectively. These results identify parameter combinations that optimize cell viability during 3D printing for multiple cell types. These results also indicate that general oxidative stress is higher in photocrosslinking conditions that induce lower cell viability. However, suppressing this increase in intracellular oxidative stress did not improve cell viability, which suggests that other stress mechanisms also contribute.

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Comparison of Mesenchymal Stem Cell Source Differentiation Toward Human Pediatric Aortic Valve Interstitial Cells within 3D Engineered Matrices

Cited by 35 publications

References 80 publications

Melatonin reverses flow shear stress‐induced injury in bone marrow mesenchymal stem cells via activation of AMP‐activated protein kinase signaling

Melatonin reverses flow shear stress‐induced injury in bone marrow mesenchymal stem cells via activation of AMP‐activated protein kinase signaling

Living nanofiber yarn-based woven biotextiles for tendon tissue engineering using cell tri-culture and mechanical stimulation

Optimizing Photo-Encapsulation Viability of Heart Valve Cell Types in 3D Printable Composite Hydrogels

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