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Bimekizumab long-term response in psoriasis: Mechanistic insights into efficacy level and durability.

BACKGROUND: Bimekizumab (BKZ), an IL-17A and IL-17F inhibitor, has demonstrated a rapid and high level of complete skin clearance in patients with psoriasis and complete normalization of the transcriptional signature of lesional skin after 8 weeks. OBJECTIVE: We sought to assess the durability of initial clinical response to BKZ for up to 4 years and investigate molecular mechanisms leading to the observed response. METHODS: Clinical data were pooled from 3 1-year phase 3 feeder studies (BE VIVID, BE READY, and BE SURE) and their 3-year open-label extension (BE BRIGHT). Transcriptomic analys

Potent efficacy of MCL-1 inhibitor-based therapies in preclinical models of mantle cell lymphoma.

Apoptosis-regulating BCL-2 family members, which can promote malignant transformation and resistance to therapy, have become prime therapeut … We also tested the MCL-1 inhibitor in primary samples from 13 MCL patients, using CD40L-expressing feeder cells to model their microenvironmental support. Notably, all unstimulated primary MCL samples were very sensitive to S63845, but the CD40L stimulation attenuated their sensitivity. Mass cytometric analysis revealed that the stimulation likely conveyed pr …

In vitro spermatogenesis: A century-long research journey, still half way around.

BACKGROUND: Spermatogenesis is one of the most complicated cellular differentiation processes in a body. Researchers struggled to find and d … animals. On looking into the history of cell culture method, it became clear that Sertoli cells as feeder cells play an important role. Even with Sertoli cells, however, spermatogenic development has been limited to small parts of spermatogenesis, a segmented period of meiotic prophase for instance. Recent developments of organoid or 3-dimensional culture tec …

Generation of electrophysiologically functional cardiomyocytes from mouse induced pluripotent stem cells.

Induced pluripotent stem (iPS) cells can efficiently differentiate into the three germ layers similar to those formed by differentiated embryonic stem (ES) cells. This provides a new source of cells in which to establish preclinical allogeneic transplantation models. Our iPS cells were generated from mouse embryonic fibroblasts (MEFs) transfected with the Yamanaka factors, the four transcription factors (Oct4, Sox2, Klf4 and c-Myc), without antibiotic selection or MEF feeders. After the formation of embryoid bodies (EBs), iPS cells spontaneously differentiated into Flk1-positive cardiac progen

Advances in corneal stem-cell transplantation in rabbits with severe ocular alkali burns.

PURPOSE: To evaluate the efficacy of autologous corneal epithelial sheet implantation in restoring transparency of rabbit corneas severely injured by alkaline and the effect of photocoagulation in arresting corneal neovessel ingrowth. SETTING: Ophthalmology Department, School of Biomedical Sciences, Universidad Austral, Buenos Aires, Argentina. METHODS: Limbal stem-cell deficiency (LSCD) was induced in 14 rabbits by alkali burns. A limbal cell biopsy was done in the contralateral eye, and the cells were cultured on a fibroblast feeder layer grown on autologous clotted platelet-poor plasma or

Comparison of the sensitivity of different geographical races of Onchocerca volvulus microfilariae to ivermectin: studies in vitro.

This study was designed to provide baseline information on the sensitivity of 4 geographical isolates of Onchocerca volvulus microfilariae (mf) (Ghana forest, Ghana savanna, Cameroon forest and Guatemala) to ivermectin, and to develop an in vitro system with which to examine parasites for the possible development of drug resistance. Drug effects were best visualized in the presence of monkey kidney (LLCMK2) feeder cells in the culture system (MEM medium+20% serum), since mf maintained in the absence of cells declined in condition rapidly. Incubation of Ghana forest mf (+cells) in ivermectin (1…

Imaging Characteristics of a Hypervascular Pituitary Spindle Cell Oncocytoma on Magnetic Resonance Imaging and Digital Subtraction Angiography.

BACKGROUND: Spindle cell oncocytomas (SCOs) are rare neuroendocrine tumors of the posterior pituitary that are often misdiagnosed as nonfunctional pituitary tumors. Fewer than 50 cases of SCOs have been described in the literature, and many of these reports have documented the tumors to be hypervascular on imaging or histology. CASE DESCRIPTION: We present the first cerebral angiography imaging findings of an SCO before primary resection. The discovery of a prominent tumor blush, enlarged meningohypophyseal feeders bilaterally, and prominent tumor draining veins aided in preoperative planning

Dynamic gelatin-based hydrogels promote the proliferation and self-renewal of embryonic stem cells in long-term 3D culture.

Long-term maintenance of embryonic stem cells (ESCs) in the undifferentiated state is still challenging. Compared with traditional 2D cultur … maintain the pluripotency of encapsulated mESCs than do traditional 2D culture methods that use MEF feeder cells or medium supplementation with GSK3β and MEK 1/2 inhibitors (2i). When cultured in GelCD hydrogels for an extended period (over 2 months) with cell passaging every 7 days, mESCs preserve their normal morphology and maintain their pluripotency and fu …

SYTO-13, a Viability Marker as a New Tool to Monitor In Vitro Pharmacodynamic Parameters of Anti-Pneumocystis Drugs.

While Pneumocystis pneumonia (PcP) still impacts the AIDS patients, it has a growing importance in immunosuppressed HIV-negative patients. To determine the anti-Pneumocystis therapeutic efficacy of new compounds, animal and in vitro models have been developed. Indeed, well-designed mouse or rat experimental models of pneumocystosis can be used to describe the in vivo anti-Pneumocystis activity of new drugs. In vitro models, which enable the screening of a large panel of new molecules, have been developed using axenic cultures or co-culture with feeder cells; but no universally accepted standar…

Impaired growth and differentiation of diploid but not immortal melanoblasts from endothelin receptor B mutant (piebald) mice.

Endothelin 3 (Edn3) and its preferred receptor, endothelin receptor B (Ednrb), are implicated in development, especially that of two neural- … . We also report for the first time a method to grow immortal melanoblasts in pure culture, without feeder cells.

Standardized pipeline for establishing, expanding, and differentiating airway and alveolar organoids from human BAL fluid.

Lung organoids are versatile experimental models, but their broader use in studying human disease is limited by the scarcity of starting material and the complexity of current methods. To align organoid technology with common clinical practice, we developed airway and alveolar organoids using cells obtained from patients' bronchoalveolar lavage (BAL) fluid. Building on existing techniques, we showed that BAL is a reliable, accessible source of primary human epithelial cells, yielding airway and alveolar organoids within 10 days. Organoids can then be expanded over many passages for downstream

Development and use of two Xenopus laevis spleen stromal cell lines to study the role of splenic stromal cells in anuran immune processes.

The spleen is an important immune organ in adult Xenopus laevis, supporting the differentiation of B cells and acting as the main peripheral lymphoid organ. Key to these processes are the supporting non-hematopoietic cells, or stromal cells, within the spleen tissue. Despite the importance of the spleen to frog immunity, few frog cell lines originating from spleen tissue have been reported. In this study, we report on the establishment and characterization of two cell lines originating from X. laevis spleen tissue, Xela S5F and Xela S5E. Morphological observations and gene expression profiling

Development of a stable chemically defined surface for the culture of human keratinocytes under serum-free conditions for clinical use.

Within the field of tissue engineering there is a need to develop new approaches to achieve effective wound closure in patients with extensive skin loss or chronic ulcers. This article exploits the well-known interdependency of epithelial keratinocytes and stromal fibroblasts in conjunction with plasma surface technology. The aim was to produce a chemically defined surface, which with the aid of a feeder layer of lethally irradiated dermal fibroblasts would improve the attachment and proliferation of the keratinocyte cell from which subconfluent cells can be transferred to wound bed models. Pl

Cancer stem cells and the cellular hierarchy in haematological malignancies.

Malignancies in the haematopoietic system seem to depend on a small subset of so-called cancer stem cells (CSC) for their continued growth and progression - this was first described as the "sleeper-feeder theory" for leukaemia. The leukaemia stem cell was the first of such subsets to be described although the origins of these cells have been difficult to dissect. Consequently, their biology is not fully elucidated, which also holds true for the normal-tissue counterparts. The stem cell concept describes stem cells to be of low frequency, self renewing and with multilineage potential based on p

Clonal analysis of the peripheral T cell compartment of the SCID-hu mouse.

Severe combined immunodeficiency (SCID) mice can be transplanted successfully with human fetal liver and thymus (SCID-hu mice). Precursor cells derived from the fetal liver differentiate in the thymus and migrate into the blood as mature T cells. In the present paper, the peripheral T cell compartment of such mice was studied. Peripheral WBC were activated by PHA and cultured in the presence of irradiated human feeder cells. The resultant cell population consisted exclusively of human CD1- CD2+ CD3+ CD7+ T lymphocytes; up to 4% of the T cells expressed the TCR gamma delta, whereas 95 to 100% w…

ROCK Inhibitor (Y-27632) Abolishes the Negative Impacts of miR-155 in the Endometrium-Derived Extracellular Vesicles and Supports Embryo Attachment.

Extracellular vesicles (EVs) are nanosized vesicles that act as snapshots of cellular components and mediate cellular communications, but they may contain cargo contents with undesired effects. We developed a model to improve the effects of endometrium-derived EVs (Endo-EVs) on the porcine embryo attachment in feeder-free culture conditions. Endo-EVs cargo contents were analyzed using conventional and real-time PCR for micro-RNAs, messenger RNAs, and proteomics. Porcine embryos were generated by parthenogenetic electric activation in feeder-free culture conditions supplemented with or without

Преодоление сопротивления CD44-overexpressing миэлома через комбинированную терапию с клетками ATRA, борцезомиба и NK.

CD44 — гликпротеин, часто переоцениваемый раком и связанный с плохим прогнозом. Мы проанализировали прогнозируемую значимость CD44 в перевыражении в миеломе (MM) и изучили терапевтическую эффективность сочетания естественной клеточной терапии убийцы (NK) с транс-ретиновой кислотой (ATRA) и борцезомибом (Bor) против CD44-overexpressing Мм. Для оценки результатов выживаемости по отношению к выражению CD44 были проанализированы клинические данные из базы данных CoMMpass. Ячейки NK были расширены за счет здоровых доноров с использованием K562-OX40L-mbIL-18/21 кормовые клетки, дополненные интерлейк

Совпадение в аннотации оригинала
CD44 is a cell-surface glycoprotein frequently overexpressed in cancers and associated with poor prognosis. We evaluated the prognostic sign … relative to CD44 expression. NK cells were expanded from healthy donors using K562-OX40L-mbIL-18/21 feeder cells supplemented with interleukin (IL)-2 and IL-15. Functional assays were performed using CD44-high myeloma cell lines treated with ATRA and Bor, individually or in combination with NK cells. Therapeutic efficacy was evaluated based on tumor growth, sy …

Optimized GMP-grade production of non-viral Sleeping Beauty-generated CARCIK cells for enhanced fitness and clinical scalability.

BACKGROUND: Strict adherence to GMP guidelines and regulatory compliance is crucial when transitioning from research to clinical-grade produ … ptimize the CARCIK differentiation process. Delaying the nucleofection step eliminated the need for feeder cells while maintaining efficient CAR expression and high cell viability. Transitioning from T-flasks to G-Rex bioreactors reduced operator hands-on time from 21 to 28 days to 14-17 days and resulted in a less differentiated CARCIK cell product. Metabolic …

[Use of cultured epidermis of human origin for demonstrating the acantholytic action of staphylococcal exfoliatin A].

Cultured human epithelia obtained from epidermal cells in vitro were used to assay the activity of staphylococcal epidermolytic toxin and develop an in vitro experimental model for the staphylococcal scalded skin syndrome. Human epidermal cells were grown from single epidermal cell suspensions obtained through trypsinization of adult normal skin into multilayered epithelia (with a basal cell layer, several intermediate and one or two upper layers) on mouse 3T3 feeder cells. First passage cultures were incubated with exfoliative toxin A from phage Group II staphylococci at various concentration…

Monoclonal antibodies to normal and abnormal epithelial antigens.

Mouse monoclonal antibodies to various human epidermal and basement membrane components were formed by immunizing Balb/c mice with ME-180, a line of human cervical carcinoma cells. The spleen cells from hyperimmunized mice were fused with a nonsecreting mouse myeloma cell line using polyethylene glycol. The resulting hybrids were selected by growth in media containing 20% fetal calf serum, hypoxanthine, thymidine, and methotrexate in RPMI-1640 in 24-well Linbro plates. Wells producing antibodies of interest were grown and eventually cloned over an HGPRT- rat fibroblast feeder layer. These cult