Cytotoxic and proliferation-inhibitory activity of natural and synthetic fungal tropolone sesquiterpenoids in various cell lines.

Fungal specialized metabolites are known for their potent biological activities, among which tropolone sesquiterpenoids (TS) stand out for their diverse bioactivities. Here, we report cytotoxic and proliferation inhibitory effects of the recently discovered TS compounds 4-hydroxyxenovulene B and 4-dihydroxy norpycnidione, and the structurally related 4-hydroxy norxenovulene B and xenovulene B. Inhibition of metabolic activity after TS treatment was observed in Jurkat, PC-3 and FAIK3-5 cells, whereas MDA-MB-231 cells were unresponsive to treatment.

A Multifunctional Nanostructured Hydrogel as a Platform for Deciphering Niche Interactions of Hematopoietic Stem and Progenitor Cells.

For over half a century, hematopoietic stem cells (HSCs) have been used for transplantation therapy to treat severe hematologic diseases. Successful outcomes depend on collecting sufficient donor HSCs as well as ensuring efficient engraftment. These processes are influenced by dynamic interactions of HSCs with the bone marrow niche, which can be revealed by artificial niche models.

On the reproducibility of extrusion-based bioprinting: round robin study on standardization in the field.

The outcome of three-dimensional (3D) bioprinting heavily depends, amongst others, on the interaction between the developed bioink, the printing process, and the printing equipment. However, if this interplay is ensured, bioprinting promises unmatched possibilities in the health care area. To pave the way for comparing newly developed biomaterials, clinical studies, and medical applications (i.

Flow-induced glycocalyx formation and cell alignment of HUVECs compared to iPSC-derived ECs for tissue engineering applications.

The relevance of cellular models highly depends on their ability to mimic the physiological environment of the respective tissue or cell niche. Static culture conditions are often unsuitable, especially for endothelial models, since they completely neglect the physiological surface shear stress and corresponding reactions of endothelial cells (ECs) such as alignment in the direction of flow. Furthermore, formation and maturation of the glycocalyx, the essential polysaccharide layer covering all endothelial surfaces and regulating diverse processes, is highly dependent on applied fluid flow.

A parallelized, perfused 3D triculture model of leukemia fordrug testing of chemotherapeutics.

Leukemia patients undergo chemotherapy to combat the leukemic cells (LCs) in the bone marrow. During therapy not only the LCs, but also the blood-producing hematopoietic stem and progenitor cells (HSPCs) may be destroyed. Chemotherapeutics targeting only the LCs are urgently needed to overcome this problem and minimize life-threatening side-effects.

The extracellular matrix of hematopoietic stem cell niches.

Hematopoietic stem cells (HSCs) are the life-long source of all types of blood cells. Their function is controlled by their direct microenvironment, the HSC niche in the bone marrow. Although the importance of the extracellular matrix (ECM) in the niche by orchestrating niche architecture and cellular function is widely acknowledged, it is still underexplored.

Fused Deposition Modeling of Microfluidic Chips in Transparent Polystyrene.

Polystyrene (PS) is one of the most commonly used thermoplastic materials worldwide and plays a ubiquitous role in today's biomedical and life science industry and research. The main advantage of PS lies in its facile processability, its excellent optical and mechanical properties, as well as its biocompatibility. However, PS is only rarely used in microfluidic prototyping, since the structuring of PS is mainly performed using industrial-scale replication processes.

Rebuilding the hematopoietic stem cell niche: Recent developments and future prospects.

Hematopoietic stem cells (HSCs) have proven their clinical relevance in stem cell transplantation to cure patients with hematological disorders. Key to their regenerative potential is their natural microenvironment - their niche - in the bone marrow (BM). Developments in the field of biomaterials enable the recreation of such environments with increasing preciseness in the laboratory.

Nitric Oxide in the Control of the Proliferation and Differentiation of Human Hematopoietic Stem and Progenitor Cells.

Hematopoietic stem and progenitor cell (HSPC) transplantation is the best-studied cellular therapy and successful control of HSPCs has wide clinical implications. Nitric oxide (NO) is a central signaling molecule and has been implicated in HSPC mobilization to the blood stream in mice. The influence of NO on HSPC behavior is, however, largely obscure due to the variety of employed cell types, NO administration systems, and used concentration ranges in the literature.

Iron Nanoparticle Composite Hydrogels for Studying Effects of Iron Ion Release on Red Blood Cell Production.

Growing numbers of complex surgical interventions increase the need for blood transfusions, which cannot be fulfilled by the number of donors. Therefore, the interest in producing erythrocytes from their precursors-the hematopoietic stem and progenitor cells (HSPCs)-in laboratories is rising. To enable this, systems are needed, which allow analysis of the effects of essential factors such as iron on erythroid development.

Limited Potential or Unfavorable Manipulations? Strategies Toward Efficient Mesenchymal Stem/Stromal Cell Applications.

Despite almost 50 years of research and over 20 years of preclinical and clinical studies, the question of curative potential of mesenchymal stem/stromal cells (MSCs) is still widely discussed in the scientific community. Non-reproducible treatment outcomes or even absence of treatment effects in comparison to control groups challenges the potential of these cells for routine application both in tissue engineering and in regenerative medicine. One of the reasons of such outcomes is non-standardized and often disadvantageous manipulation of MSCs prior therapy.

Monitoring matrix remodeling in the cellular microenvironment using microrheology for complex cellular systems.

Multiple particle tracking (MPT) microrheology was employed for monitoring the development of extracellular matrix (ECM) mechanical properties in the direct microenvironment of living cells. A customized setup enabled us to overcome current limitations: (i) Continuous measurements were enabled using a cell culture chamber, with this, matrix remodeling by fibroblasts in the heterogeneous environment of macroporous scaffolds was monitored continuously. (ii) Employing tracer laden porous scaffolds for seeding human mesenchymal stem cells (hMSCs), we followed conventional differentiation protocols.

Potential of electrospun cationic BSA fibers to guide osteogenic MSC differentiation via surface charge and fibrous topography.

Large or complex bone fractures often need clinical treatments for sufficient bone repair. New treatment strategies have pursued the idea of using mesenchymal stromal cells (MSCs) in combination with osteoinductive materials to guide differentiation of MSCs into bone cells ensuring complete bone regeneration. To overcome the challenge of developing such materials, fundamental studies are needed to analyze and understand the MSC behavior on modified surfaces of applicable materials for bone healing.

Migration Assay for Leukemic Cells in a 3D Matrix Toward a Chemoattractant.

In leukemia, leukemic cells hijack the hematopoietic stem cell (HSC) microenvironment in the bone marrow-the so-called stem cell niche-by flooding the niche with clonal progeny of leukemic cells. They can exploit signaling pathways which are critical for HSC development to support their own survival, homing, and maintenance. These interactions of leukemic cells with the microenvironment have an impact on therapy progress and patient outcome.

Microfluidic Shear Force Assay to Determine Cell Adhesion Forces.

Cell adhesion is implicated in many physiological settings such as the retention of hematopoietic stem cells (HSCs) in their bone marrow niches or their migration into the bloodstream. During HSC mobilization these adhesion sites are cleaved and have to be newly formed during HSC homing and engraftment. To determine the adhesive properties of HSCs on different extracellular matrix (ECM) molecules, we present a microfluidic shear force assay, where a laminar flow is used to detach a semi-adherent cell population, the HSC model cell line KG-1a, from an ECM protein-coated substrate.

3D models of the bone marrow in health and disease: yesterday, today and tomorrow.

The complex interaction between hematopoietic stem cells (HSCs) and their microenvironment in the human bone marrow ensures a life-long blood production by balancing stem cell maintenance and differentiation. This so-called HSC niche can be disturbed by malignant diseases. Investigating their consequences on hematopoiesis requires deep understanding of how the niches function in health and disease.

Biomimetic 3D in vitro model of biofilm triggered osteomyelitis for investigating hematopoiesis during bone marrow infections.

Unlabelled: In this work, we define the requirements for a human cell-based osteomyelitis model which overcomes the limitations of state of the art animal models. Osteomyelitis is a severe and difficult to treat infection of the bone that develops rapidly, making it difficult to study in humans. We have developed a 3D in vitro model of the bone marrow, comprising a macroporous material, human hematopoietic stem and progenitor cells (HSPCs) and mesenchymal stromal cells (MSCs).

Magnetic Macroporous Hydrogels as a Novel Approach for Perfused Stem Cell Culture in 3D Scaffolds via Contactless Motion Control.

There is an urgent need for 3D cell culture systems that avoid the oversimplifications and artifacts of conventional culture in 2D. However, 3D culture within the cavities of porous biomaterials or large 3D structures harboring high cell numbers is limited by the needs to nurture cells and to remove growth-limiting metabolites. To overcome the diffusion-limited transport of such soluble factors in 3D culture, mixing can be improved by pumping, stirring or shaking, but this in turn can lead to other problems.

Bioinstructive Coatings for Hematopoietic Stem Cell Expansion Based on Chemical Vapor Deposition Copolymerization.

We report the chemical vapor deposition (CVD) of dual-functional polymer films for the specific and orthogonal immobilization of two biomolecules (notch ligand delta-like 1 (DLL1) and an RGD-peptide) that govern the fate of hematopoietic stem and progenitor cells. The composition of the CVD polymer and thus the biomolecule ratio can be tailored to investigate and optimize the influence of the relative surface concentrations of biomolecules on stem cell behavior. Prior to cell experiments, all surfaces were characterized by infrared reflection adsorption spectroscopy, time-of-flight secondary ion mass spectrometry, and X-ray photoelectron spectroscopy to confirm the presence of both biomolecules.

3D models of the hematopoietic stem cell niche under steady-state and active conditions.

Hematopoietic stem cells (HSCs) in the bone marrow are able to differentiate into all types of blood cells and supply the organism each day with billions of fresh cells. They are applied to cure hematological diseases such as leukemia. The clinical need for HSCs is high and there is a demand for being able to control and multiply HSCs in vitro.

Direct Mapping of RAFT Controlled Macromolecular Growth on Surfaces via Single Molecule Force Spectroscopy.

Single molecule force spectroscopy (SMFS) is employed to gain insight into reversible addition-fragmentation chain transfer (RAFT) polymerization processes with living characteristics on glass surfaces. Surface-initiated (SI)-RAFT was selected to grow poly(hydroxyethyl methacrylate) (PHEMA). After aminolysis of the RAFT chain termini, thiol moieties serve as anchoring points for the gold tip of an atomic force microscope.

Fabrication of biofunctionalized, cell-laden macroporous 3D PEG hydrogels as bone marrow analogs for the cultivation of human hematopoietic stem and progenitor cells.

In vitro proliferation of hematopoietic stem cells (HSCs) is yet an unresolved challenge. Found in the bone marrow, HSCs can undergo self-renewing cell division and thereby multiply. Recapitulation of the bone marrow environment in order to provide the required signals for their expansion is a promising approach.

Biomimetic macroporous PEG hydrogels as 3D scaffolds for the multiplication of human hematopoietic stem and progenitor cells.

Multiplication of hematopoietic stem cells (HSCs) in vitro with current standard methods is limited and mostly insufficient for clinical applications of these cells. They quickly lose their multipotency in culture because of the fast onset of differentiation. In contrast, HSCs efficiently self-renew in their natural microenvironment (their niche) in the bone marrow.

Surface Properties of Nanostructured Bio-Active Interfaces: Impacts of Surface Stiffness and Topography on Cell-Surface Interactions.

Due to their ability to confer key functions of the native extracellular matrix (ECM) poly(ethylene glycol) (PEG)-based and PEG-modified materials have been extensively used as biocompatible and biofunctionalized substrate systems to study the influence of environmental parameters on cell adhesion Given wide-ranging recent evidence that ECM compliance influences a variety of cell functions, the detailed determination and characterization of the specific PEG surface characteristics including topography, stiffness and chemistry is required. Here, we studied two frequently used bio-active interfaces - PEG-based and PEG-modified surfaces - to elucidate the differences between the physical surface properties, which cells can sense and respond to. For this purpose, two sets of surfaces were synthesized: the first set consisted of nanopatterned glass surfaces containing RGD-functionalized gold nanoparticles surrounded by a passivated PEG-silane layer and the second set consisted of PEG-diacrylate (PEG-DA) hydrogels decorated with RGD-functionalized gold nanoparticlesAlthough the two sets of nanostructured materials compared here were highly similar in terms of density and geometrical distribution of the presented bio-ligands as well as in terms of mechanical bulk properties, the topography and mechanical properties of the surfaces were found to be substantially different and are described in detail.

Regulation of hematopoietic stem cell behavior by the nanostructured presentation of extracellular matrix components.

Hematopoietic stem cells (HSCs) are maintained in stem cell niches, which regulate stem cell fate. Extracellular matrix (ECM) molecules, which are an essential part of these niches, can actively modulate cell functions. However, only little is known on the impact of ECM ligands on HSCs in a biomimetic environment defined on the nanometer-scale level.