Bone marrow‐on‐a‐chip: Long‐term culture of human haematopoietic stem cells in a three‐dimensional microfluidic environment

Sieber, Stefan; Wirth, Lorenz; Cavak, Nino; Koenigsmark, Marielle; Marx, Uwe; Lauster, Roland; Rosowski, Mark

doi:10.1002/term.2507

Cited by 160 publications

(168 citation statements)

References 40 publications

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“…Therefore, multi material bioprinting seems to be an ideal technology to create an in vitro model with blended bioinks. The bioprinted articular cartilage constructs could extend a previously published bone marrow model to a complete tissue engineered in vitro femoral head describing joint diseases like osteoarthritis. Furthermore, bioprinting technology becomes crucial in enhancing tissue models mimicking human in vivo organ interaction.…”

Section: Resultsmentioning

confidence: 99%

Photopolymerizable gelatin and hyaluronic acid for stereolithographic 3D bioprinting of tissue‐engineered cartilage

Lam¹,

et al. 2019

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To create artificial cartilage in vitro, mimicking the function of native extracellular matrix (ECM) and morphological cartilage‐like shape is essential. The interplay of cell patterning and matrix concentration has high impact on the phenotype and viability of the printed cells. To advance the capabilities of cartilage bioprinting, we investigated different ECMs to create an in vitro chondrocyte niche. Therefore, we used methacrylated gelatin (GelMA) and methacrylated hyaluronic acid (HAMA) in a stereolithographic bioprinting approach. Both materials have been shown to support cartilage ECM formation and recovery of chondrocyte phenotype. We used these materials as bioinks to create cartilage models with varying chondrocyte densities. The models maintained shape, viability, and homogenous cell distribution over 14 days in culture. Chondrogenic differentiation was demonstrated by cartilage‐typical proteoglycan and type II collagen deposition and gene expression (COL2A1, ACAN) after 14 days of culture. The differentiation pattern was influenced by cell density. A high cell density print (25 × 106 cells/mL) led to enhanced cartilage‐typical zonal segmentation compared to cultures with lower cell density (5 × 106 cells/mL). Compared to HAMA, GelMA resulted in a higher expression of COL1A1, typical for a more premature chondrocyte phenotype. Both bioinks are feasible for printing in vitro cartilage with varying differentiation patterns and ECM organization depending on starting cell density and chosen bioink. The presented technique could find application in the creation of cartilage models and in the treatment of articular cartilage defects using autologous material and adjusting the bioprinted constructs size and shape to the patient. © 2019 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2649–2657, 2019.

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Section: Resultsmentioning

confidence: 99%

Photopolymerizable gelatin and hyaluronic acid for stereolithographic 3D bioprinting of tissue‐engineered cartilage

Lam¹,

et al. 2019

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“…Contrarily to traditional animal testing systems, whose use poses ethical issues and limits the translation of obtained results to human patients due to inherent species‐specific differences, and 2‐D systems, which lack the complexity of in vivo microenvironments, in vitro 3‐D co‐cultured models of HSPC and supportive MSC in a microfluidic environment can help improving our capacity to successfully mimic the BM niche. Such an approach has been followed by Sieber and co‐workers whose 3‐D co‐culture model, based on a hydroxyapatite coated zirconium oxide scaffold comprising human BM MSC inserted in a microfluidic device, was capable of supporting the long‐term culture of primitive HSPC . Equally exploiting a microfluidic device, BMP2‐ and BMP4‐loaded collagen scaffolds were implanted subcutaneously into mice so that native cells and vasculature would migrate and develop on the chip‐sized bone matrix, ultimately resembling a BM compartment that was built in vivo throughout 8 weeks after transplantation.…”

Section: Biomaterial‐supported Cultures Of Hspc In Bioreactorsmentioning

confidence: 99%

Hematopoietic Niche – Exploring Biomimetic Cues to Improve the Functionality of Hematopoietic Stem/Progenitor Cells

Costa

Soure

Cabral

et al. 2017

Biotechnology Journal

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The adult bone marrow (BM) niche is a complex entity where a homeostatic hematopoietic system is maintained through a dynamic crosstalk between different cellular and non-cellular players. Signaling mechanisms triggered by cell-cell, cell-extracellular matrix (ECM), cell-cytokine interactions, and local microenvironment parameters are involved in controlling quiescence, self-renewal, differentiation, and migration of hematopoietic stem/progenitor cells (HSPC). A promising strategy to more efficiently expand HSPC numbers and tune their properties ex vivo is to mimic the hematopoietic niche through integration of adjuvant stromal cells, soluble cues, and/or biomaterial-based approaches in HSPC culture systems. Particularly, mesenchymal stem/stromal cells (MSC), through their paracrine activity or direct contact with HSPC, are thought to be a relevant niche player, positioning HSPC-MSC co-culture as a valuable platform to support the ex vivo expansion of hematopoietic progenitors. To improve the clinical outcome of hematopoietic cell transplantation (HCT), namely when the available HSPC are present in a limited number such is the case of HSPC collected from umbilical cord blood (UCB), ex vivo expansion of HSPC is required without eliminating the long-term repopulating capacity of more primitive HSC. Here, we will focus on depicting the characteristics of co-culture systems, as well as other bioengineering approaches to improve the functionality of HSPC ex vivo.

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“…Moreover longer wavelengths in near‐IR exhibit too much absorption in water molecules. Example applications of the two‐photon microscopy are imaging of single cells trapped in a microfluidic channel and a bone‐on‐a‐chip platform . An example output image is shown in Figure e.…”

Section: Imaging Approaches For Static Platformsmentioning

confidence: 99%

Optical Imaging Approaches to Monitor Static and Dynamic Cell‐on‐Chip Platforms: A Tutorial Review

Arandian

Bagheri

Ehtesabi

et al. 2019

Small

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Miniaturized laboratories on chip platforms play an important role in handling life sciences studies. The platforms may contain static or dynamic biological cells. Examples are a fixed medium of an organ‐on‐a‐chip and individual cells moving in a microfluidic channel, respectively. Due to feasibility of control or investigation and ethical implications of live targets, both static and dynamic cell‐on‐chip platforms promise various applications in biology. To extract necessary information from the experiments, the demand for direct monitoring is rapidly increasing. Among different microscopy methods, optical imaging is a straightforward choice. Considering light interaction with biological agents, imaging signals may be generated as a result of scattering or emission effects from a sample. Thus, optical imaging techniques could be categorized into scattering‐based and emission‐based techniques. In this review, various optical imaging approaches used in monitoring static and dynamic platforms are introduced along with their optical systems, advantages, challenges, and applications. This review may help biologists to find a suitable imaging technique for different cell‐on‐chip studies and might also be useful for the people who are going to develop optical imaging systems in life sciences studies.

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Bone marrow‐on‐a‐chip: Long‐term culture of human haematopoietic stem cells in a three‐dimensional microfluidic environment

Cited by 160 publications

References 40 publications

Photopolymerizable gelatin and hyaluronic acid for stereolithographic 3D bioprinting of tissue‐engineered cartilage

Photopolymerizable gelatin and hyaluronic acid for stereolithographic 3D bioprinting of tissue‐engineered cartilage

Hematopoietic Niche – Exploring Biomimetic Cues to Improve the Functionality of Hematopoietic Stem/Progenitor Cells

Optical Imaging Approaches to Monitor Static and Dynamic Cell‐on‐Chip Platforms: A Tutorial Review

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