Survival of Human Bone Marrow Plasma Cells In Vitro Depends on the Support of the Stromal Cells, PI3K, and Canonical NF-kappaB Signaling.

Contrary to short-lived plasma cells, which survive only 3-5 days, long-lived plasma cells (LLPCs) contribute to the humoral memory of the body and thus also to many antibody-related diseases. The ability of plasma cells to persist over months, years, and even a lifetime has been demonstrated in vivo. Yet, the in vitro culture of human primary bone marrow-derived plasma cells has been limited to a few days.

Cutting Edge: Serum but Not Mucosal Antibody Responses Are Associated with Pre-Existing SARS-CoV-2 Spike Cross-Reactive CD4 T Cells following BNT162b2 Vaccination in the Elderly.

Advanced age is a main risk factor for severe COVID-19. However, low vaccination efficacy and accelerated waning immunity have been reported in this age group. To elucidate age-related differences in immunogenicity, we analyzed human cellular, serological, and salivary SARS-CoV-2 spike glycoprotein-specific immune responses to the BNT162b2 COVID-19 vaccine in old (69-92 y) and middle-aged (24-57 y) vaccinees compared with natural infection (COVID-19 convalescents, 21-55 y of age).

Pilot investigation on the dose-dependent impact of irradiation on primary human alveolar osteoblasts in vitro.

Radiotherapy of head and neck squamous cell carcinoma can lead to long-term complications like osteoradionecrosis, resulting in severe impairment of the jawbone. Current standard procedures require a 6-month wait after irradiation before dental reconstruction can begin. A comprehensive characterization of the irradiation-induced molecular and functional changes in bone cells could allow the development of novel strategies for an earlier successful dental reconstruction in patients treated by radiotherapy.

An Individual Patient's "Body" on Chips-How Organismoid Theory Can Translate Into Your Personal Precision Therapy Approach.

The first concepts for reproducing human systemic organismal biology were developed over 12 years ago. Such concepts, then called human- or body-on-a-chip, claimed that microphysiological systems would become the relevant technology platform emulating the physiology and morphology of human organisms at the smallest biologically acceptable scale and, therefore, would enable the selection of personalized therapies for any patient at unprecedented precision. Meanwhile, the first human organoids-stem cell-derived complex three-dimensional organ models that expand and self-organize -have proven that self-assembly of minute premature human organ-like structures is feasible, once the respective stimuli of ontogenesis are provided to human stem cells.

Cross-reactive CD4 T cells enhance SARS-CoV-2 immune responses upon infection and vaccination.

The functional relevance of preexisting cross-immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a subject of intense debate. Here, we show that human endemic coronavirus (HCoV)–reactive and SARS-CoV-2–cross-reactive CD4 T cells are ubiquitous but decrease with age. We identified a universal immunodominant coronavirus-specific spike peptide (S816-830) and demonstrate that preexisting spike- and S816-830–reactive T cells were recruited into immune responses to SARS-CoV-2 infection and their frequency correlated with anti–SARS-CoV-2-S1-IgG antibodies.

3D bioprinting of tissue-specific osteoblasts and endothelial cells to model the human jawbone.

Jawbone differs from other bones in many aspects, including its developmental origin and the occurrence of jawbone-specific diseases like MRONJ (medication-related osteonecrosis of the jaw). Although there is a strong need, adequate in vitro models of this unique environment are sparse to date. While previous approaches are reliant e.

Comparison of the Translational Potential of Human Mesenchymal Progenitor Cells from Different Bone Entities for Autologous 3D Bioprinted Bone Grafts.

Reconstruction of segmental bone defects by autologous bone grafting is still the standard of care but presents challenges including anatomical availability and potential donor site morbidity. The process of 3D bioprinting, the application of 3D printing for direct fabrication of living tissue, opens new possibilities for highly personalized tissue implants, making it an appealing alternative to autologous bone grafts. One of the most crucial hurdles for the clinical application of 3D bioprinting is the choice of a suitable cell source, which should be minimally invasive, with high osteogenic potential, with fast, easy expansion.

The microfollicle: a model of the human hair follicle for in vitro studies.

Access to complex in vitro models that recapitulate the unique markers and cell-cell interactions of the hair follicle is rather limited. Creation of scalable, affordable, and relevant in vitro systems which can provide predictive screens of cosmetic ingredients and therapeutic actives for hair health would be highly valued. In this study, we explore the features of the microfollicle, a human hair follicle organoid model based on the spatio-temporally defined co-culture of primary cells.

Vascular bioprinting with enzymatically degradable bioinks via multi-material projection-based stereolithography.

Introduction of cavities and channels into 3D bioprinted constructs is a prerequisite for recreating physiological tissue architectures and integrating vasculature. Projection-based stereolithography inherently offers high printing speed with high spatial resolution, but so far has been incapable of fabricating complex native tissue architectures with cellular and biomaterial diversity. The use of sacrificial photoinks, i.

Inspired by the human placenta: a novel 3D bioprinted membrane system to create barrier models.

Barrier organ models need a scaffold structure to create a two compartment culture. Technical filter membranes used most often as scaffolds may impact cell behaviour and present a barrier themselves, ultimately limiting transferability of test results. In this work we present an alternative for technical filter membrane systems: a 3D bioprinted biological membrane in 24 well format.

Toxicity of topically applied drugs beyond skin irritation: Static skin model vs. Two organs-on-a-chip.

Skin model cultivation under static conditions limits the observation of the toxicity to this single organ. Biology-inspired microphysiological systems associating skin with a liver in the same circulating medium provide a more comprehensive insight into systemic substance toxicity; however, its advantages or limitations for topical substance toxicity remain unknown. Herein, we performed topical (OECD test guideline no.

SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the rapidly unfolding coronavirus disease 2019 (COVID-19) pandemic. Clinical manifestations of COVID-19 vary, ranging from asymptomatic infection to respiratory failure. The mechanisms that determine such variable outcomes remain unresolved.

Effects of 5-aza-2´-deoxycytidine on primary human chondrocytes from osteoarthritic patients.

Chondrocytes, comparable to many cells from the connective tissue, dedifferentiate and end up in a similar fibroblastoid cell type, marked by the loss of the specific expression pattern. Here, chondrocytes isolated from osteoarthritic (OA) patients were investigated. The OA chondrocytes used in this work were not affected by the loss of specific gene expression upon cell culture.

Reconstructed human skin shows epidermal invagination towards integrated neopapillae indicating early hair follicle formation in vitro.

Application of reconstructed human Skin (RhS) is a promising approach for the treatment of extensive wounds and for drug efficacy and safety testing. However, incorporating appendages, such as hair follicles, into RhS still remains a challenge. The hair follicle plays a critical role in thermal regulation, dispersion of sweat and sebum, sensory and tactile functions, skin regeneration, and repigmentation.

Autologous induced pluripotent stem cell-derived four-organ-chip.

Microphysiological systems play a pivotal role in progressing toward a global paradigm shift in drug development. Here, we designed a four-organ-chip interconnecting miniaturized human intestine, liver, brain and kidney equivalents. All four organ models were predifferentiated from induced pluripotent stem cells from the same healthy donor and integrated into the microphysiological system.

Emulating the early phases of human tooth development in vitro.

Functional in vitro models emulating the physiological processes of human organ formation are invaluable for future research and the development of regenerative therapies. Here, a developmentally inspired approach is pursued to reproduce fundamental steps of human tooth organogenesis in vitro using human dental pulp cells. Similar to the in vivo situation of tooth initiating mesenchymal condensation, a 3D self-organizing culture was pursued resulting in an organoid of the size of a human tooth germ with odontogenic marker expression.

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

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.

Simultaneous evaluation of anti-EGFR-induced tumour and adverse skin effects in a microfluidic human 3D co-culture model.

Antibody therapies targeting the epithelial growth factor receptor (EGFR) are being increasingly applied in cancer therapy. However, increased tumour containment correlates proportionally with the severity of well-known adverse events in skin. The prediction of the latter is not currently possible in conventional in vitro systems and limited in existing laboratory animal models.

Bioengineering of a Full-Thickness Skin Equivalent in a 96-Well Insert Format for Substance Permeation Studies and Organ-On-A-Chip Applications.

The human skin is involved in protecting the inner body from constant exposure to outer environmental stimuli. There is an evident need to screen for toxicity and the efficacy of drugs and cosmetics applied to the skin. To date, animal studies are still the standard method for substance testing, although they are currently controversially discussed Therefore, the multi-organ chip is an attractive alternative to replace animal testing.

Bioprinting Perfusion-Enabled Liver Equivalents for Advanced Organ-on-a-Chip Applications.

Many tissue models have been developed to mimic liver-specific functions for metabolic and toxin conversion in in vitro assays. Most models represent a 2D environment rather than a complex 3D structure similar to native tissue. To overcome this issue, spheroid cultures have become the gold standard in tissue engineering.

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

Multipotent haematopoietic stem and progenitor cells (HSPCs) are the source for all blood cell types. The bone marrow stem cell niche in which the HSPCs are maintained is known to be vital for their maintenance. Unfortunately, to date, no in vitro model exists that accurately mimics the aspects of the bone marrow niche and simultaneously allows the long-term culture of HSPCs.

Study of Viral Vectors in a Three-dimensional Liver Model Repopulated with the Human Hepatocellular Carcinoma Cell Line HepG2.

This protocol describes the generation of a three-dimensional (3D) ex vivo liver model and its application to the study and development of viral vector systems. The model is obtained by repopulating the extracellular matrix of a decellularized rat liver with a human hepatocyte cell line. The model permits studies in a vascularized 3D cell system, replacing potentially harmful experiments with living animals.

Bipolar radio-frequency-induced thermofusion of intestinal tissue - In vivo evaluation of a new fusion technique in an experimental study.

Purpose: Bipolar radio-frequency-induced thermofusion (BiRTh) of intestinal tissue might replace conventional stapling devices which are associated with technical and functional complications. Previous results of our study group confirmed the feasibility to fuse intestinal tissue using BiRTh-induced thermofusion ex vivo. The aim of this study was now to evaluate the efficacy of fusing intestinal tissue in vivo by BiRTh-induced thermofusion.

Emulating human microcapillaries in a multi-organ-chip platform.

Current microfluidic chip-based tissue culture systems lack a capillary endothelial vessel system, which would enable perfusion with blood. We utilise spatial cell cultures to populate a perfused multi-organ-chip platform-a microfluidic device recently introduced for substance testing. Complete biological vascularization of such culture systems is vital to properly emulate physiological tissue behaviour.

Use of a three-dimensional humanized liver model for the study of viral gene vectors.

Reconstituted three-dimensional (3D) liver models obtained by engrafting hepatic cells into an extracellular matrix (ECM) are valuable tools to study tissue regeneration, drug action and toxicology ex vivo. The aim of the present study was to establish a system for the functional investigation of a viral vector in a 3D liver model composed of human HepG2 cells on a rat ECM. An adeno-associated viral (AAV) vector expressing the Emerald green fluorescent protein (EmGFP) and a short hairpin RNA (shRNA) directed against human cyclophilin b (hCycB) was injected into the portal vein of 3D liver models.