A cell bank paradigm for preclinical evaluation of an analogous cellular product for an allogeneic cell therapy.

Toward the translation of allogeneic cell therapy products, cell banks are needed not only to manufacture the final human product but also during the preclinical evaluation of an animal-based analogous cellular product (ACP). These cell banks need to be established at both the master cell bank (MCB) level and the working cell bank (WCB) level. Inasmuch as most of the development of cell therapy products is at academic centers, it is imperative that academic researchers understand how to establish MCBs and WCBs within an academic environment.

A transcriptomic taxonomy of mouse brain-wide spinal projecting neurons.

The brain controls nearly all bodily functions via spinal projecting neurons (SPNs) that carry command signals from the brain to the spinal cord. However, a comprehensive molecular characterization of brain-wide SPNs is still lacking. Here we transcriptionally profiled a total of 65,002 SPNs, identified 76 region-specific SPN types, and mapped these types into a companion atlas of the whole mouse brain.

Characterization of the Age-Related Differences in Porcine Acetabulum and Femoral Head Articular Cartilage.

Objective: The use of porcine animal models for cartilage injury has increased recently due to their similarity with humans with regard to cartilage thickness, limited intrinsic healing of chondral defects, and joint loading biomechanics. However, variations in the mechanical and biochemical properties of porcine hip articular cartilage among various tissue ages and weightbearing (WB) regions are still unknown. This study's aim was to characterize the mechanical and biochemical properties of porcine hip articular cartilage across various ages and WB regions.

BAX activation in mouse retinal ganglion cells occurs in two temporally and mechanistically distinct steps.

Background: Pro-apoptotic BAX is a central mediator of retinal ganglion cell (RGC) death after optic nerve damage. BAX activation occurs in two stages including translocation of latent BAX to the mitochondrial outer membrane (MOM) and then permeabilization of the MOM to facilitate the release of apoptotic signaling molecules. As a critical component of RGC death, BAX is an attractive target for neuroprotective therapies and an understanding of the kinetics of BAX activation and the mechanisms controlling the two stages of this process in RGCs is potentially valuable in informing the development of a neuroprotective strategy.

BAX activation in mouse retinal ganglion cells occurs in two temporally and mechanistically distinct steps.

Background Pro-apoptotic BAX is a central mediator of retinal ganglion cell (RGC) death after optic nerve damage. BAX activation occurs in two stages including translocation of latent BAX to the mitochondrial outer membrane (MOM) and then permeabilization of the MOM to facilitate the release of apoptotic signaling molecules. As a critical component of RGC death, BAX is an attractive target for neuroprotective therapies and an understanding of the kinetics of BAX activation and the mechanisms controlling the two stages of this process in RGCs is potentially valuable in informing the development of a neuroprotective strategy.

Characterization of the Temporomandibular Joint Disc Complex in the Yucatan Minipig.

The temporomandibular joint (TMJ) disc complex (i.e., the TMJ disc and its six attachments) is crucial to everyday functions such as mastication and speaking.

Proteomic, mechanical, and biochemical development of tissue-engineered neocartilage.

Background: The self-assembling process of cartilage tissue engineering is a promising technique to heal cartilage defects, preventing osteoarthritic changes. Given that chondrocytes dedifferentiate when expanded, it is not known if cellular expansion affects the development of self-assembled neocartilage. The objective of this study was to use proteomic, mechanical, and biochemical analyses to quantitatively investigate the development of self-assembled neocartilage derived from passaged, rejuvenated costal chondrocytes.

Core transcription programs controlling injury-induced neurodegeneration of retinal ganglion cells.

Regulatory programs governing neuronal death and axon regeneration in neurodegenerative diseases remain poorly understood. In adult mice, optic nerve crush (ONC) injury by severing retinal ganglion cell (RGC) axons results in massive RGC death and regenerative failure. We performed an in vivo CRISPR-Cas9-based genome-wide screen of 1,893 transcription factors (TFs) to seek repressors of RGC survival and axon regeneration following ONC.

Incidentally found focal xanthogranulomatous pyelonephritis with extensive venous thrombus.

A 71-year-old woman with history of asthma presented with 2 months history of shortness of breath; on imaging an incidental left renal mass was noted. Subsequent renal protocol CT was obtained that showed a 4.5 cm left upper pole exophytic mass with renal vein thrombus extending into the inferior vena cava to the level of the caudate lobe concerning for renal cell carcinoma.

Opioid-Limiting Pain Control After Transurethral Resection of the Prostate: A Randomized Controlled Trial.

Objective: To assess whether a multimodal opioid-limiting protocol and patient education intervention can reduce postoperative opioid use following transurethral resection of the prostate.

Methods: This prospective, non-blinded, single-institution, randomized controlled trial (NCT04102566) assigned 50 patients undergoing a transurethral resection of the prostate to either a standard of care control (SOC) or multimodal experimental group (MMG). The intervention included adding ibuprofen to the postoperative pain regimen, promoting appropriate opioid use while hospitalized, an educational intervention, and discharging without opioid prescription.

Stiffness- and Bioactive Factor-Mediated Protection of Self-Assembled Cartilage against Macrophage Challenge in a Novel Co-Culture System.

Objective: Tissue-engineered cartilage implants must withstand the potential inflammatory and joint loading environment for successful long-term repair of defects. The work's objectives were to develop a novel, direct cartilage-macrophage co-culture system and to characterize interactions between self-assembled neocartilage and differentially stimulated macrophages.

Design: In study 1, it was hypothesized that the proinflammatory response of macrophages would intensify with increasing construct stiffness; it was expected that the neocartilage would display a decrease in mechanical properties after co-culture.

Proteomic, mechanical, and biochemical characterization of cartilage development.

The objective of this work is to examine the development of porcine cartilage by analyzing its mechanical properties, biochemical content, and proteomics at different developmental stages. Cartilage from the knees of fetal, neonatal, juvenile, and mature pigs was analyzed using histology, mechanical testing, biochemical assays, fluorophore-assisted carbohydrate electrophoresis, and bottom-up proteomics. Mature cartilage has 2.

The functionality and translatability of neocartilage constructs are improved with the combination of fluid-induced shear stress and bioactive factors.

Neocartilage tissue engineering aims to address the shortcomings of current clinical treatments for articular cartilage indications. However, advancement is required toward neocartilage functionality (mechanical and biochemical properties) and translatability (construct size, gross morphology, passage number, cell source, and cell type). Using fluid-induced shear (FIS) stress, a potent mechanical stimulus, over four phases, this work investigates FIS stress' efficacy toward creating large neocartilage derived from highly passaged minipig costal chondrocytes, a species relevant to the preclinical regulatory process.

The Effect of Neonatal, Juvenile, and Adult Donors on Rejuvenated Neocartilage Functional Properties.

Cartilage does not naturally heal, and cartilage lesions from trauma and wear-and-tear can lead to eventual osteoarthritis. To address long-term repair, tissue engineering of functional biologic implants to treat cartilage lesions is desirable, but the development of such implants is hindered by several limitations, including (1) donor tissue scarcity due to the presence of diseased tissues in joints, (2) dedifferentiation of chondrocytes during expansion, and (3) differences in functional output of cells dependent on donor age. Toward overcoming these challenges, (1) costal cartilage has been explored as a donor tissue, and (2) methods have been developed to rejuvenate the chondrogenic phenotype of passaged chondrocytes for generating self-assembled neocartilage.

Isolation and characterization of porcine macrophages and their inflammatory and fusion responses in different stiffness environments.

Evaluating the host immune response to biomaterials is an essential step in the development of medical devices and tissue engineering strategies. To aid in this process, studies, whereby immune cells such as macrophages are cultured on biomaterials, can often expedite high throughput testing of many materials prior to implantation. While most studies to date utilize murine or human cells, the use of porcine macrophages has been less well described, despite the prevalent use of porcine models in medical device and tissue engineering development.

BCLX gene therapy moderates neuropathology in the DBA/2J mouse model of inherited glaucoma.

Axonal degeneration of retinal ganglion cells (RGCs) causes blindness in glaucoma. Currently, there are no therapies that target axons to prevent them from degenerating. Activation of the BAX protein has been shown to be the determining step in the intrinsic apoptotic pathway that causes RGCs to die in glaucoma.

The Influence of Mitochondrial Dynamics and Function on Retinal Ganglion Cell Susceptibility in Optic Nerve Disease.

The important roles of mitochondrial function and dysfunction in the process of neurodegeneration are widely acknowledged. Retinal ganglion cells (RGCs) appear to be a highly vulnerable neuronal cell type in the central nervous system with respect to mitochondrial dysfunction but the actual reasons for this are still incompletely understood. These cells have a unique circumstance where unmyelinated axons must bend nearly 90° to exit the eye and then cross a translaminar pressure gradient before becoming myelinated in the optic nerve.

Knee orthopedics as a template for the temporomandibular joint.

Although the knee joint and temporomandibular joint (TMJ) experience similar incidence of cartilage ailments, the knee orthopedics field has greater funding and more effective end-stage treatment options. Translational research has resulted in the development of tissue-engineered products for knee cartilage repair, but the same is not true for TMJ cartilages. Here, we examine the anatomy and pathology of the joints, compare current treatments and products for cartilage afflictions, and explore ways to accelerate the TMJ field.

Impact of catheter size on pain and continence following robotic prostatectomy.

Unlabelled: INTRODUCTION Continence and catheter related pain following prostatectomy are significant patient concerns, and it is unknown whether catheter size impacts these variables. In this study, patients undergoing prostatectomy were randomized to receive either a 16 French or 20 French catheter to assess the impact of catheter size on postoperative continence and pain.

Materials And Methods: Patients were prospectively randomized to receive either a 16 French or a 20 French latex catheter at the completion of prostatectomy.

BAX-Depleted Retinal Ganglion Cells Survive and Become Quiescent Following Optic Nerve Damage.

Removal of the Bax gene from mice completely protects the somas of retinal ganglion cells (RGCs) from apoptosis following optic nerve injury. This makes BAX a promising therapeutic target to prevent neurodegeneration. In this study, Bax mice were used to test the hypothesis that lowering the quantity of BAX in RGCs would delay apoptosis following optic nerve injury.

Remaining Hurdles for Tissue-Engineering the Temporomandibular Joint Disc.

The temporomandibular joint (TMJ) disc, a fibrocartilaginous structure between the mandible and temporal bone, is implicated in temporomandibular disorders (TMDs). TMDs symptomatically affect approximately 25% of the population, of which 70% have internal derangement of the disc. Treatments lack efficiency, motivating novel therapies, including tissue-engineering toward TMJ disc regeneration.

Considerations for translation of tissue engineered fibrocartilage from bench to bedside.

Fibrocartilage is found in the knee meniscus, the temporomandibular joint (TMJ) disc, the pubic symphysis, the annulus fibrosus of intervertebral disc, tendons, and ligaments. These tissues are notoriously difficult to repair due to their avascularity, and limited clinical repair and replacement options exist. Tissue engineering has been proposed as a route to repair and replace fibrocartilages.