Advances in biological research have been greatly influenced by the development of organoids, a specialized form of 3D cell culture. Created from pluripotent stem cells, organoids are effective in vitro models in replicating the structure and progression of brain development, providing an exceptional tool for studying the complexities of biology. Among these, cortical organoids, comprising in part of neurons, have been instrumental in providing early insights into brain formation, function, and pathology. Functional characteristics of cortical organoids, such as cellular morphology and electrophysiology, provide physiological insight into cellular states and are crucial for understanding the roles of cell types within their specific niches. And while progress has been made studying engineered neuronal systems, decoding the functional properties of neuronal networks and their role in producing behaviors depends in part on recognizing neuronal cell types, their general locations within the brain, and how they connect.

Worldwide, over 2.5 million people live with spinal cord injury, with over 100,000 new cases occurring annually. Spinal cord injury often causes motor dysfunction below the level of the injury. For example, thoracic and lumbar spinal cord injury can cause paraplegia and cervical spinal cord injury can cause quadriplegia. Such injury is permanent and often severe and there is no effective treatment. Various neurologic diseases also involve damaged or dysfunctional spinal cord neurons. Neural stem cell grafts have potential for treating such conditions. However, it has not been possible to obtain sufficient numbers of appropriately patterned neural stem cells, having a spinal cord positional identity, for implanted cells to survive and functionally engraft.

Stem cells have the potential to develop into different types of cells. They are key to an organism’s development. Producing stem cell lines are important for research. Currently, avian embryonic stems cells are cultured on a layer of feeder cells. Feeder cells ensure that the stem cells survive and do not differentiate into other types of cells. However, using feeder cells can be costly and inconvenient.

Researchers at UC Irvine have identified and tested a molecular target that regulates T cell function during chronic viral infection and cancer. The molecular target is one of the high mobility group proteins (HMGB2). HMGB2 is a DNA binding protein that regulates transcriptional processes, meaning that its modulation will have profound effects on T cell differentiation and ultimate function by altering the expression of many genes.

Researchers at UC Irvine have developed an organoid culture system capable of generating three-dimensional molecular gradients. This recapitulates in vivo tissue development more accurately than current two-dimensional organoid culture systems and will allow scientists to study human-specific disease mechanisms in native tissue.

Although hematopoietic stem cells (HSCs) are useful in a variety of treatments, HSC donation is a difficult procedure. The original transplantation is commonly extracted from the bone marrow manually, a long and potentially painful procedure. Other techniques for mobilizing HSC to the bloodstream involve a 5-day regimen of G-CSF treatment, that has significant side effects of fatigue, nausea, and bone pain. UC Santa Cruz researchers developed a treatment that allows collection of HSC from blood in a 2-hour treatment using already FDA-approved drugs. This makes both the cost and overall comfort of patient donating HSC’s significantly easier.

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Brief description not available

The present invention features a method and device that addresses the need for a low-cost and easy-to-use method and device to pattern a sharp interface between two or more cell populations or, more generally, two or more coatings wherein their interfacing properties are of interest. As a result, the present invention enables new types of experiments that analyze cell-cell interactions and the study of tissue biology in general. 

This invention illustrates that the secretome of hESCs, iPSCs and moreover, ALS patients’ iPSCs, robustly protect neuronal cells from apoptosis, diminish mislocalization of TDP43, and significantly improve the formation and maintenance of neurites of ALS-MNs. Such neuro-protection manifests in the genetic and in an acquired neuro-toxicity models. Importantly, administration of CM form ALS-iPSCs (ALS iPSC-CM) to transgenic mice that model human disease (SOD1G93A) prevented MN degeneration, maintained the innervation (neuro-muscular junctions), delayed onset of symptoms, and prolonged lifespan. Comparative proteomics and fractionation of conditioned medium outline specific proteins and fractions that are responsible for this neuroprotection. Translationally, this work suggests the rapid development of a new therapeutic for ALS.

Researchers at the University of California, Davis have developed a method of synthesizing stem cell-derived, exosome-mimicking, nanovesicles that have the therapeutic potential to rescue apoptotic neurons in culture.

UCLA researchers in the Department of Bioengineering have developed a novel electrically conductive scaffold system with a hyaluronic acid (HA)-based hydrogel for biomimetic research to treat spinal cord and other central nervous system (CNS) injuries.

Astrocytes are the most abundant central nervous system cell type and have been implicated in the pathobiology of many neurological diseases. The present invention describes a rapid and reproducible method to create functional human astrocytes (iAstrocytes) using induced pluripotent stem cells which can be used to study astrocyte biology and their role in neurological diseases.

The heart consists of a multitude of diverse cardiomyocyte cell types, including atrial, ventricular and pacemaker cells, which cooperate to ensure proper cardiac function and circulation throughout the body. The rhythm of the heart beat is regulated by the sinoatrial node (SAN), functionally known as the cardiac pacemaker. Loss or dysfunction of these pacemaker cardiomyocytes leads to severe cardiac arrhythmias, syncope and/or even death. Although artificial pacemakers exist to help overcome these issues, several serious limitations and problems have emerged with this approach over the past several decades including electrode fracture or damage to insulation, infection, re-operations for battery exchange, and venous thrombosis. Moreover, size mismatch and the fact that pacemaker leads do not grow with children are a concerning problem. Thus, replacing artificial pacemakers with biological pacemakers potentially overcomes these artificial pacemaker issues including the expense and complications associated with device replacement, device or lead failure, and infection. To achieve these goals, understanding how pacemaker cardiomyocytes are generated is necessary to develop a human biological pacemaker for cardiac cellular therapies.

Natural killer (NK) cells are a key component of the innate immune system and are involved in early defense against viruses and cancer cells. NK cells have the ability to lyse cells without prior sensitization  and therefore are the subject of intense interest to be potentially used as immunotherapeutic targets to treat cancer. The crucial element for using NK cells in immunotherapy is the ability to control the signaling and activation pathways. Recent work has shown that the cytokine-inducible SH2-containing protein (CIS), encoded by the Cish gene, can act as a checkpoint in NK activation by inhibiting IL-15 signaling, a major upregulator of NK cell activity. Furthermore, deletion of the Cish gene has been shown to increase the sensitivity of NK cells to IL-15, resulting in mice that are resistant to experimental metastasis.

Researchers at UCLA have developed an approach to construct an embryonic kidney in vitro for the treatment of end stage renal disease.

UCLA researchers in the Department of Medicine and the Department of Surgery have developed a novel lentiviral vector that expresses a codon-optimized sequence of a T cell receptor (TCR) specific for the cancer-testis antigen NY-ESO-1 as well as a positron emission tomography (PET) reporter and suicide gene HSV1-sr39tk for use in adoptive T cell therapy for cancer treatment.

Researchers at the UCLA Department of Microbiology, Immunology and Molecular Genetics have developed methods for efficient gene editing in stem cells by increasing the level of apoptosis regulator BCL-2.

Hematopoietic stem cell (HSC) transplants are used to treat patients with a broad spectrum of hematological malignancies, immune disorders and genetic blood diseases. Unfortunately, even after decades of use and research, there is a significant shortage of histocompatible HSCs available for transplants. Transplanting larger numbers of HSCs increases the likelihood and speed of successful engraftment, which can reduce the risk of complications such as anemia and infection, and more effectively treat underlying disease. The inability to efficiently maintain adult HSCs ex vivo is also a significant barrier for the wider development and implementation of gene therapies for diverse blood diseases and a major obstacle for engineering HSC derived cellular products for immunotherapy. One approach to overcome this challenge is to develop a means to maintain and expand HSCs in culture. Unfortunately, there is no well-defined reproducible means to maintain or expand HSCs. Even short culture times in optimized conditions are deleterious to HSCs. Ex vivo HSC maintenance and expansion could significantly enhance their clinical utility in a wide range of human diseases, providing a new platform for testing drugs, enabling more efficient gene editing within stem cells, and developing into a widely-used tool for the research community.

UCLA researchers have developed a novel method for enriching, expanding, and maturing populations of skeletal muscle progenitor cells (SMPCs) from human pluripotent stem cells (hPSCs).

Researchers led by Paul Weiss from the Department of Chemistry and Pediatrics at UCLA have created a new microfluidic device for high-throughput gene editing of cells.

Researchers at the UCLA Department of Microbiology, Immunology & Molecular Genetics have developed novel methods to achieve efficient, precise gene integration and effective expression of cDNA cassettes to express normal versions of genes in hematopoietic stem cells.

A plate manufactured to enable samples of cells, microorganisms, proteins, DNA, biomolecules, transfectants, and other biological media to be positioned at specific sites. Some or all of the sites are built from removable material so that samples may be isolated.

Rett syndrome (RTT) is a devastating disease that affects 1 in every 10,000 children born in the United States, primarily females. RTT patients undergo apparently normal development until 6-18 months of age, followed by impaired motor function, stagnation and then regression of developmental skills, hypotonia, seizures and a spectrum of autistic behaviors. Rett syndrome is a rare disease that shares certain pathways with major developmental disorders such as autism and schizophrenia, increasing the potential impact. There is no cure for Rett syndrome and the animal model does not entirely recapitulate the human disease. Thus, having the possibility to screen drugs directly in human neurons is a major milestone.

Historically, the understanding of the development and pathophysiology of the human brain has been studied by examination of post-mortem and diseased specimens in conjunction with non-human primates and mouse models. The understanding of complex biological mechanisms is driven by advancement of techniques and new model systems and recent advances in stem technologies have contributed to the advancement of our knowledge of human neural development. Moreover, the reprograming of human somatic cells into induced pluripotent stem cells (iPSCs) which can be redirected to a specific cell fate has led to a breakthrough in neurobiology research. These findings have led to the generation of human brain organoids from IPSCs.