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The cerebral organoids in existence today fall far short of earning the “brain” label, mini or otherwise.But a trio of recent publications suggests that cerebral-organoid science may be turning a corner—and that the future of such brain studies may depend less on trying to create tiny perfect replicas of whole brains and more on creating highly replicable modules of developing brain parts that can be snapped together like building blocks.Veritable colleges of mini-brains were soon thriving under various protocols in laboratories around the world.Much to the frustration of impatient experimentalists, however, the mini-brains’ similarity to the real thing only went so far.Their shrunken anatomies were distorted; they lacked blood vessels and layers of tissue; neurons were present but important glial cells that make up the supportive white matter of the brain were often missing.Worst of all was the organoids’ inconsistency: They differed too much from one another.
A proposal to create a living model of the human retina, the light-sensitive tissue at the back of the eye, won $90,000 in the National Eye Institute (NEI) 3-D Retina Organoid Challenge (3-D ROC).The NEI 3-D ROC is an initiative that seeks to design human retinas from stem cells.An estimated 285 million people worldwide are visually impaired, including 39 million who are blind.For many, vision loss results from degenerative retinal diseases such as age-related macular degeneration, glaucoma, and diabetic retinopathy.In 2011, Japanese researchers demonstrated that embryonic mouse stem cells could be used in the lab to generate retinal tissue.The submitted 3-D ROC concepts were evaluated based on their innovativeness and feasibility.
A collaboration between researchers in Japan and the United States has led to a new microdevice that successfully forms fascicles in the lab.The report, which can be read in Stem Cell Reports, is expected to provide important insights on brain development and disease.Many scientists have examined axon development and degeneration in two-dimensional (2D) systems.However, it is becoming increasingly apparent that the fascicle's 3D structure has an essential role in axon function.Because fascicles are disrupted in many neurodegenerative diseases such as ALS, the research group theorized that understanding their formation could give clues on the prevention of a number of diseases.To form axon fascicles, the research teams manufactured a microdevice in which human neurons derived from induced pluripotent stem cells were injected.
After several labs successfully implanted human brain organoids into rats, many scientists are questioning the ethical implications of the experiment, STAT News reports.Nearly four years ago, scientists in Vienna discovered that they could create organoids – lentil-sized blobs of human brain tissue – from stem cells.The revolutionary discovery has helped advance research on human brain development, Alzheimer’s, and Zika virus.These human brain organoids existed solely in test tubes, until this past weekend, when two teams of neuroscientists reported successfully implanting these cells into the brains of rats and mice.The scientists also observed neurological activity – when they shone a light in the rodent’s eyes, connected neurons lit up in the implanted organoid.Other labs reported connecting the human brain organoids to blood vessels in the rodents.
CINCINNATI - Seven years ago Cincinnati Children's scientists first used pluripotent stem cells to mimic natural human development and grow working human intestine in a lab.Today medical center doctors can bioengineer the gastrointestinal tissues of sick children to find clues about a child's disease and how to treat it.Organoid technology has the potential to solve several current medical and research challenges, according to Aaron Zorn, PhD, the new organoid center's director.The technology gives researchers a first-in-class physiological platform for laboratory research on living diseased tissue, which cannot be done on patients.It can provide laboratory human modeling systems in a petri dish for developing and testing drugs before expensive clinical trials.The new center is organized to be a highly collaborative, multi-disciplinary center of excellence that integrates scientists, physicians, geneticists, bioengineers and entrepreneurs, according to Zorn.
New Rochelle, NY, December 5,2017--A new study describes a unique bioengineered tissue construct, or organoid, into which colorectal cancer cells are embedded, creating a model of the tumor and surrounding extracellular matrix (ECM).Researchers can use this model to study how the physical features of the ECM affect the behavior, growth, and even susceptibility to chemotherapy, as described in an article published in Tissue Engineering, Part A, peer-reviewed journal from Mary Ann Liebert, Inc., publishers.Outstanding Student Award, which will be presented at the TERMIS Americas meeting on December 6th to coauthor Mahesh Devarasetty, PhD, Wake Forest School of Medicine.In the article entitled "Bioengineered Submucosal Organoids for in vitro Modeling of Colorectal Cancer," coauthors Devarasetty, Shay Soker, PhD and colleagues from Wake Forest School of Medicine and Wake Forest Baptist Medical Center, Winston-Salem, NC, report on the method they developed to produce the submucosal organoids using primary smooth muscle cells embedded in collagen hydrogel.The authors propose that in the future these organoids could be made using a patient's own cells for personalized medicine applications."Our increasing understanding of tumor architecture is guiding the development of tumor extracellular matrix 'mimics' that better reflect the tumor microenvironment and thereby create more realistic systems for assessing tumor cell behavior in response to treatment," says Tissue Engineering Co-Editor-in-Chief Peter C. Johnson, MD, Principal, MedSurgPI, LLC and President and CEO, Scintellix, LLC, Raleigh, NC.
CINCINNATI - Before medical science can bioengineer human organs in a lab for therapeutic use, two remaining hurdles are ensuring genetic stability--so the organs are free from the risk of tumor growth--and producing organ tissues of sufficient volume and size for viable transplant into people.Scientists from the Cincinnati Children's Center for Stem Cell and Organoid Medicine and Yokohama City University (YCU) in Japan report in Stem Cell Reports achieving both goals with a new production method for bioengineered human gut and liver tissues.The protocol is designed to mimic natural embryonic development, and CDX2 is a molecular marker found in gut tissues, according to Takanori Takebe, MD, lead investigator on the study and a physician at Cincinnati Children's and YCU.Although PGECs are still at an embryonic development stage, they're already programmed to form the gastrointestinal (GI) tract.Next, study authors used additional series of progressive genetic and biochemical manipulations, telling PGECs to form human hindgut and liver organoids."Compared to gastrointestinal organoids and liver-generated directly from induced pluripotent stem cells, generation from PGECs resulted in robust and genetically stable formation of different tissue GI types, without causing benign tumors called teratomas," said first author Ran-Ran Zhang, PhD, a research fellow at Cincinnati Children's.
(BOSTON) -- The small intestine is the main site where we digest and absorb nutrients and minerals from food, and it is also a place where many intestinal infections occur and digestive and inflammatory disorders manifest themselves.This prevents the study of dynamic processes involving the intestinal barrier, including nutrient and drug transport, as well as its interactions with the microbiome.In addition, organoids lack a vasculature and the mechanical movements caused by normal peristalsis and blood flow, which are vital for many processes in the gut, including its regeneration and control of bacterial overgrowth.In an effort to overcome these limitations, a team at the Wyss Institute for Biologically Inspired Engineering led by its Founding Director, Donald Ingber, M.D., Ph.D., had previously engineered a microfluidic "Organ-on-a-Chip" (Organ Chip) culture device in which cells from a human intestinal cell line originally isolated from a tumor were cultured in one of two parallel running channels, separated by a porous matrix-coated membrane from human blood vessel-derived endothelial cells in the adjacent channel."We are now able to leverage the organoid approach to isolate intestinal stem cells from human biopsies, but we break up the organoids and culture the patient-specific cells within our Organ Chips where they spontaneously form intestinal villi oriented towards the channel lumen, and the epithelium in close apposition to human intestinal microvascular endothelium," said Ingber, who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School (HMS) and the Vascular Biology Program at Boston Children's Hospital, as well as Professor of Bioengineering at Harvard's John A. Paulson School of Engineering and Applied Sciences (SEAS)."This approach presents a new stepping stone for the investigation of normal and disease-related processes in a highly personalized manner, including the transport of nutrients, digestion, different intestinal disorders, and intestinal interactions with commensal microbes as well as pathogens."
A competition for radical ideas in the fight against blindness will move to its next phase by challenging participants to build functioning human retina prototypes.The National Eye Institute (NEI) 3-D Retina Organoid Challenge (NEI 3-D ROC 2020) is a $1-million federal prize competition designed to generate lab-grown human retinas from stem cells.Organoids developed for the competition will mimic the structure, organization, and function of the human retina, the light-sensitive tissue in the back of the eye.Expedited development of new treatments for the 285 million people worldwide who are visually impaired, including 39 million who are blind, are desperately needed.Efforts to understand and cure vision-depleting retinal diseases such as age-related macular degeneration and diabetic retinopathy are limited by the lack of tissue models."Mini-retinas" developed under 3-D ROC 2020 would replicate the complexity and functionality of the human retina, and serve as a platform to study underlying causes of retinal diseases, test new drug therapies, and provide a source of cells for transplantation.
Brains fold in on themselves as they grow.How and why they do it is a different story, and studying it requires some pretty interesting science.“Here, we present an on-chip approach, which enables development of human brain organoids to millimeter diameter,” the team of researchers led by Orly Reiner at the Weizmann Institute of Science in Israel wrote in the study published recently in Nature Physics.Organoids aren’t entire miniature organs.Rather, they’re collections of stem cells that develop into the specific organ cells.Millimetre-scale brain organoids can die without access to blood vessels, and thick tissue can be difficult to image with microscopes, according to the paper.
Cold Spring Harbor, NY -- Patient-derived organoids, hollow spheres of cells cultured from tumors, can quickly and accurately predict how patients with pancreatic cancer respond to a variety of treatments, facilitating a precision-medicine approach to the deadly disease.That is the conclusion of an international team of researchers led by David Tuveson, Cold Spring Harbor Laboratory (CSHL) Professor and Chief Scientist for The Lustgarten Foundation."We've been able to identify an approach to prioritize treatment strategies for pancreas cancer patients, with the goal of giving them the best shot at survival and the best shot at a good quality of life," says Dr. Hervé Tiriac, a researcher in Tuveson's lab and first author of a paper reporting the findings.With only 8 percent of patients surviving 5 years beyond their diagnosis, pancreatic cancer is one of the deadliest cancer types.Currently, surgical removal of the cancerous tissue is the only effective treatment, but because the disease progresses so quickly, only 15 percent of patients are eligible for the procedure.Because so few patients have their tumors surgically removed, obtaining enough high-quality samples of pancreatic cancer has been challenging.
BAR HARBOR, MAINE -- The MDI Biological Laboratory has announced that it received more than $70,000 in cash and in-kind awards for its inaugural "Applications of Organoid Technology" course, held May 27 through June 2 on the institution's Bar Harbor campus.The awards included contributions from Baker, Corning, the Cystic Fibrosis Foundation, Nikon, Leica, Novartis Pharmaceuticals Corp., STEMCELL Technologies, Fisher Scientific and ThermoFisher Scientific.De Jonge has been a visiting scientist at the MDI Biological Laboratory since 2008.The course was offered in partnership with Hubrecht Organoid Technology (The HUB), a non-profit organization based in Utrecht, Netherlands.The HUB was founded to implement the pioneering work of Hans Clevers, M.D., Ph.D., who discovered methods to grow stem cell-derived three dimensional mini-organs from the tissues of patients."Organoid technology has tremendous potential for human health," said Kevin Strange, Ph.D., president of the MDI Biological Laboratory.
New York, NY (July 25, 2018) - In a collaborative study between Case Western Reserve University School of Medicine, the New York Stem Cell Foundation (NYSCF) Research Institute, and George Washington University, researchers have developed a new procedure for generating miniature 3D versions of the brain called "organoids" from human stem cells.By providing an environment for cells to interact the way they would in an actual human brain, brain organoids allow researchers to observe brain development, study disease, and test promising new drugs.The new technique, published online today in Nature Methods, creates the first organoids capable of myelination, modeling the brain's structure and function more closely than ever."NYSCF is committed to accelerating treatments for neurological diseases, and developing better ways for the community to use stem cells for disease research is a key part of achieving that goal," says Susan L. Solomon, NYSCF CEO."This new method grew out of a longstanding collaboration enabled by the NYSCF community, and we are incredibly proud of the work that has resulted from this partnership."The study was led by NYSCF - Robertson Stem Cell Investigator Alumnus Paul Tesar, PhD, the Dr. Donald and Ruth Weber Goodman Professor of Innovative Therapeutics and associate professor of genetics and genome sciences at Case Western Reserve University School of Medicine.
Researchers at the University of California San Diego School of Medicine have developed a rapid, cost-effective method to grow organoid “mini-brains” in a lab.These miniature brains, which replicate the architecture of brains but possess no level of consciousness, are created using stem cells.The researchers hope that these mini-brains will allow us to gain a better understanding of the real brains that they replicate.“The brain is one of the most complex tissues in the body,” Alysson Muotri, director of the Stem Cell Program at UCSD School of Medicine, told Digital Trends.“While we have a good idea of anatomy and how the adult brain work, the understanding of human brain neurodevelopment is at a very mysterious stage.There [is little information] about how the brain develops, [and] when it starts to function, yet there are many neurological disorders that starts in utero.
CINCINNATI - Scientists working to bioengineer the entire human gastrointestinal system in a laboratory now report using pluripotent stem cells to grow human esophageal organoids.Published in the journal Cell Stem Cell the study is the latest advancement from researchers at the Cincinnati Children's Center for Stem Cell and Organoid Medicine (CuSTOM).The center is developing new ways to study birth defects and diseases that affect millions of people with gastrointestinal disorders, such as gastric reflux, cancer, etc.The newly published research is the first time scientists have been able to grow human esophageal tissue entirely from pluripotent stem cells (PSCs), which can form any tissue type in the body, according to the authors.Cincinnati Children's scientists and their multi-institutional collaborators already have used PSCs to bioengineer human intestine, stomach, colon and liver."In addition to being a new model to study birth defects like esophageal atresia, the organoids can be used to study diseases like eosinophilic esophagitis and Barrett's metaplasia, or to bioengineer genetically matched esophageal tissue for individual patients."
A research group led by scientists from Showa University and the RIKEN Center for Biosystems Dynamics Research in Japan have, for the first time, succeeded in growing three-dimensional salivary gland tissue that, when implanted into mice, produced saliva like normal glands.The alternative is to use embryonic stem cells or induced pluripotent stem (iPS) cells--which have the ability to transform into many types of cell to create what is called an organoid--a simplified three-dimensional tissue that resembles the structure of a real organ.Growing functional organoids in the laboratory would enable patients with failing organs to recover at least some of the functions that the original organs had.For the present study, published in Nature Communications, the researchers, led by Professor Kenji Mishima of Showa University and Takashi Tsuji of RIKEN BDR, took on the challenge of recreating salivary gland tissue.Salivary glands are important for digesting starch and for facilitating swallowing, but can be damaged by an autoimmune condition known as Sjogren's syndrome or by radiation therapy for cancer.They identified two transcription factors--Sox9 and Foxc1-as being key to the differentiation of stem cells into salivary gland tissue, and also identified a pair of signaling chemicals--FGF7 and FGF10-which induced cells expressing those transcription factors to differentiate into salivary gland tissue.
Eye can barely believe it, but it's true.Researchers at John Hopkins University in Maryland created eyeball parts from stem cells in the hopes of better understanding the how and why we developed "trichromatic vision" -- the ability to see in red, blue and green.The study was published in Science on Oct. 12.Organoids are built from a small number of stem cells in a 3D suspension, which eventually multiply to form something akin to an organ system.The eye organoid used in the John Hopkins study produces a miniature retina, the layer of cells at the back of the eyeball that process light, creating the electrical impulses the brain can use to produce vision.First, the team confirmed that their retina-organoids-in-a-dish were functioning similarly to human retinas.
The researchers demonstrate the physiological relevance of this process during infection and have published their findings in Nature Communications.The bacterial Gram-positive pathogen C. difficile is a major healthcare-associated infection that can cause pseudomembranous colitis in patients following antibiotic treatment, and the main contributor of gastroenteritis-associated deaths in the US and Europe.The bacterium produces two secreted toxins that induce a cytotoxic response in intestinal epithelial cells (IECs) that form the protective mucosal barrier of the intestinal tract.However, the underlying mechanisms of this host-pathogen interaction were unclear, and it was unknown whether this cytotoxic response played a protective or detrimental role to the host.They combined the results of studies in these ex vivo cultured organoid systems with in vivo infection studies in transgenic mice in which key host genes were specifically deleted in the gut epithelial layer while leaving expression in other tissues intact.This allowed them to dissect the mechanisms underlying the molecular interactions of C. difficile with the host's intestinal barrier and to establish how this process contributes to pathogenesis.
WINSTON-SALEM, N.C. - DEC. 17, 2018 - Scientists at the Wake Forest Institute for Regenerative Medicine (WFIRM) have recently developed a process that may change the way cancer of the appendix is treated in the future.Researchers at WFIRM, in collaboration with the Department of Surgery - Surgical Oncology at Wake Forest Baptist Medical Center, have created a patient-specific tumor 'organoid' model to identify the most effective treatment for each tumor.Data on appendix cancer is difficult to come by since it is a rare disease, affecting only 1 in 100,000 people.This is complicated further because every patient responds differently to the many chemotherapy treatments available.Skardal, along with Konstantinos Votanopoulos, M.D., Ph.D., from Wake Forest Baptist, were the lead investigators on the study recently published in the Annals of Surgical Oncology.Cells from this biopsy are then used to grow small tumors called 'organoids' in the lab which behave similarly to the original tumor.