A pre-conditioning protocol of peripheral blood derived endothelial colony forming cells for endothelialization of tissue engineered constructs

Kraus, Xenia; Pflaum, Michael; Thoms, Stefanie; Jonczyk, Rebecca; Witt, Martin; Scheper, Thomas; Blume, Cornelia

doi:10.1016/j.mvr.2020.104107

Cited by 11 publications

(9 citation statements)

References 59 publications

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“…Conversely, the glycocalyx has also crucial mechano-sensing functions to mediate shear stress induced signaling cascades into the cells, resulting in cytoskeletal remodeling, control stiffness and height of the ECs [48]. Most importantly, shear stress is also a crucial signal for the upregulation of the anti-thrombogenic surface protein thrombomodulin [49], which also was significantly upregulated in the flow exposed cells of this study. A pivotal transcription factor needed for these shear stress activated cell responses is KLF2 [50], which also was found to be significantly upregulated in this study under flow conditions, however, on both coated HFM.…”

Section: Discussionmentioning

confidence: 60%

Towards Biohybrid Lung Development—Fibronectin-Coating Bestows Hemocompatibility of Gas Exchange Hollow Fiber Membranes by Improving Flow-Resistant Endothelialization

et al. 2021

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To provide an alternative treatment option for patients with end-stage lung disease, we aim for biohybrid lung development (BHL) based on hollow fiber membrane (HFM) technology used in extracorporeal membrane oxygenators. For long-term BHL application, complete hemocompatibility of all blood-contacting surfaces is indispensable and can be achieved by their endothelialization. Indeed, albumin/heparin (AH) coated HFM enables initial endothelialization, but as inexplicable cell loss under flow conditions was seen, we assessed an alternative HFM coating using fibronectin (FN). Therefore, endothelial cell (EC) adherence and viability on both coated HFM were analyzed by fluorescence-based staining. Functional leukocyte and thrombocyte adhesion assays were performed to evaluate hemocompatibility, also in comparison to blood plasma coated HFM as a clinically relevant control. To assess monolayer resistance and EC behavior under clinically relevant flow conditions, a mock circulation setup was established, which also facilitates imitation of lung-disease specific blood gas settings. Besides quantification of flow-associated cell loss, endothelial responses towards external stimuli, like flow exposure or TNFα stimulation, were analyzed by qRT-PCR, focusing on inflammation, thrombus formation and extracellular matrix production. Under static conditions, both coated HFM enabled the generation of a viable, confluent, non-inflammatory and anti-thrombogenic monolayer. However, by means of homogenous FN coating, cell retention and physiologic gene regulation towards an improved hemocompatible-and extracellular matrix producing phenotype, was significantly superior compared to the inhomogeneous AH coating. In summary, our adaptable in-house FN coating secures the endothelial requirements for long-term BHL application and may promote monolayer establishment on all other blood contacting surfaces of the BHL (e.g., cannulae).

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Section: Discussionmentioning

confidence: 60%

Towards Biohybrid Lung Development—Fibronectin-Coating Bestows Hemocompatibility of Gas Exchange Hollow Fiber Membranes by Improving Flow-Resistant Endothelialization

et al. 2021

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“…Luo et al [15] used human iPS on PGA scaffolds, and in his approach, the bio-hybrid vessel was stimulated by stretching in a bioreactor system, which had an augmenting effect on collagen synthesis and SMC proliferation. Dynamic cultivation therefore is important not only to induce anti-thrombogenic markers [8], but makes a difference in terms of biomechanical stability.…”

Section: Dynamic Cultivation In a Bioreactormentioning

confidence: 99%

“…(A) Schematic of a bioreactor setup for in vitro cultivation of a TEVG with external control unit for parallelization of cultivation processes; (B) Demonstration of assembled Bioreactor Setup [24] Pressure here was applied intermittently or uniformly to support the maturation of differentiated endothelial cells (e.g., indicated by vascular endothelial growth factor receptor-2, von-Willebrand-factor or vascular endothelialcadherin), or SMCs (e.g., α-smooth muscle actin or smooth muscle myosin heavy chain) [26,27]. In addition, cells developed an anti-thrombogenic gene profile [8]. Besides conditioning cell phenotypes, bioreactors were used to train and test stability of the matured vascular graft, and here a pressure load up to 2000 mbar and a suture tear strength of up to 3 mm/min have been realized in comparable systems [28].…”

Section: Monitoring and Control Of Physical Conditionsmentioning

confidence: 99%

“…In this context, Uzurski described umbilical cord scaffolds with HUVECs that successfully generated nitric oxide when exposed to undulating pulsing in a bioreactor [79]. Von Hafften et al showed, that cyclic pulsatile flow had an anti-inflammatory effect on macrophages ; ECFCs (MSS: medium shear stress = 5 dynes/cm 2 ; HSS = high shear stress of 20 dynes/cm 2 ; Scale in all images: 100 μm); adopted from [8] and fibroblasts invading a successfully endothelialized "electrospun" PCL/N,N′-bis(trimethylsilyl)urea-scaffold. Future dynamic cultivation concepts should therefore take also variable pulsatile flow into account [80].…”

Section: Conditioning Of Cellsmentioning

confidence: 99%

“…The resulting vascular grafts unfortunately revealed an inferior biomechanical stability in nude rats, possibly due to the fact, that the differentiation process did not reach the quality of end‐differentiated contractile SMCs. Besides the research on stem cells, other concepts are being developed for autologous cells in high cell numbers [ 8 ].…”

Section: Which Innovations Are Needed and Why?mentioning

confidence: 99%

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Vascular implants – new aspects for in situ tissue engineering

Blume

Kraus

Heene

et al. 2022

Engineering in Life Sciences

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Conventional synthetic vascular grafts require ongoing anticoagulation, and autologous venous grafts are often not available in elderly patients. This review highlights the development of bioartificial vessels replacing brain-dead donoror animal-deriving vessels with ongoing immune reactivity. The vision for such bio-hybrids exists in a combination of biodegradable scaffolds and seeding with immune-neutral cells, and here different cells sources such as autologous progenitor cells or stem cells are relevant. This kind of in situ tissue engineering depends on a suitable bioreactor system with elaborate monitoring systems, three-dimensional (3D) visualization and a potential of cell conditioning into the direction of the targeted vascular cell phenotype. Necessary bioreactor tools for dynamic and pulsatile cultivation are described. In addition, a concept for design of vasa vasorum is outlined, that is needed for sustainable nutrition of the wall structure in large caliber vessels. For scaffold design and cell adhesion additives, different materials and technologies are discussed. 3D printing is introduced as a relatively new field with promising prospects, for example, to create complex geometries or micro-structured surfaces for optimal cell adhesion and ingrowth in a standardized and custom designed procedure. Summarizing, a bio-hybrid vascular prosthesis from a controlled biotechnological process is thus coming more and more into view. It has the potential to withstand strict approval requirements applied for advanced therapy medicinal products.

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Vascular Functional Recovery and Reparation by Human Endothelial Progenitor Cells

Berezin

2022

Handbook of Stem Cell Therapy

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A pre-conditioning protocol of peripheral blood derived endothelial colony forming cells for endothelialization of tissue engineered constructs

Cited by 11 publications

References 59 publications

Towards Biohybrid Lung Development—Fibronectin-Coating Bestows Hemocompatibility of Gas Exchange Hollow Fiber Membranes by Improving Flow-Resistant Endothelialization

Towards Biohybrid Lung Development—Fibronectin-Coating Bestows Hemocompatibility of Gas Exchange Hollow Fiber Membranes by Improving Flow-Resistant Endothelialization

Vascular implants – new aspects for in situ tissue engineering

Vascular Functional Recovery and Reparation by Human Endothelial Progenitor Cells

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