A team of postdoctoral and research scientists at the Wellcome Sanger Institute and MRC Cancer Unit has made data sets of
human and mouse immune and stromal cells openly accessible on a preview site that provides initial access to data for the Human Cell Atlas initiative, before these have been published.
The research, conducted in
human and mouse immune cells, appears online in the journal Proceedings of the National Academy of Sciences.
Not exact matches
Hoping to learn something about how the
human body defends itself against cancer, he had zeroed in on a complex regiment of lymphocytes called T cells, common to the
immune systems in both
mouse and man.
In that paper, Weitzmann, Ofotokun,
and their colleagues described bone loss similar to that observed in
humans following the reconstitution of the T cell population in
immune - compromised
mice (similar to T - cell expansion following ART).
The study examined specific
immune pathways known to be activated during flu infections in both
humans and mice, which makes the findings relevant to children.
An inflammatory protein that triggers a pregnant
mouse's
immune response to an infection or other disease appears to cause brain injury in her fetus, but not the premature birth that was long believed to be linked with such neurologic damage in both rodents
and humans, new Johns Hopkins - led research suggests.
A decade ago, he replicated the entire
human leukemia disease process by introducing oncogenes into normal
human blood cells, transplanting them into xenografts (special
immune - deficient
mice that accept
human grafts)
and watching leukemia develop — a motherlode discovery that has guided leukemia research ever since.
Even the new studies clashed somewhat: Unlike the UCSF study, the German research found no major differences between the overall microbiomes of twins with
and without MS. Finally,
mouse models of MS are not perfect mimics of the
human disease,
and mouse immune systems aren't identical to people's.
An unknown component of breast milk appears to kill HIV particles
and virus - infected cells, as well as blocking HIV transmission in
mice with a
human immune system.
Senior author Madhav Dhodapkar, M.D., the Arthur H.
and Isabel Bunker Professor of Medicine
and Immunobiology,
and chief of Hematology, said the study, using tissue
and blood samples from
humans and mice, shows that chronic stimulation of the
immune system by lipids made in the context of inflammation underlies the origins of at least a third of all myeloma cases.
Concerned that the
immune systems of clean
mice might not be good proxies for the
human immune system — no
human is brought up in such clean conditions
and fed such clean food — they housed lab
mice with
mice from a pet store.
«This is primarily because of the difference between the
mouse and human immune systems.»
The authors said that this result suggests that the reason bacterial numbers are so high in these
mice,
and, by extension,
human LAD patients, is not because of a defect in the
immune system's surveillance mechanism but because of the inflammation caused by the
immune system's abnormal response to normal levels of bacteria in the gums.
The researchers used «humanized
mice,» which have had their
immune systems replaced with
human immune system cells, thymus tissue
and bone marrow.
The researchers then introduced the two strains into
mice transplanted with a
human immune system
and watched in real time as HIV spread from one CD4 + helper T cell to another.
And when implants were placed in
mice modified to have
human immune systems, their bodies didn't reject the material, which persisted for up to 3 months.
2 - D cell - culture
and mouse experiments also provided key evidence of the virus's modus operandi; although the rodent brain doesn't harbor the full contingent of
human neural stem cells, it has blood vessels
and immune - system components that organoids lack.
They found that indeed, they do,
and that stimulating these cells led them to kill cells infected with HIV - 1 derived from latently infected cells, both in culture
and in
mice engineered to have a
human immune system.
Researchers developed a new type of cell transplantation to treat
mice mimicking a rare lung disease that one day could be used to treat this
and other
human lung diseases caused by dysfunctional
immune cells.
Now, scientists have modified Salmonella bacteria to trigger a particularly powerful
immune response against
human cancer cells implanted in
mice, shrinking the tumors
and — for the first time — preventing them from metastasizing.
A single gene appears to play a crucial role in coordinating the
immune system
and metabolism,
and deleting the gene in
mice reduces body fat
and extends lifespan, according to new research by scientists at the Jean Mayer USDA
Human Nutrition Research Center (USDA HNRCA) on Aging at Tufts University
and Yale University School of Medicine.
Human tumor tissue or cell lines can be coengrafted into these mouse models, providing a powerful tool for studying the interactions between human immune cells and human can
Human tumor tissue or cell lines can be coengrafted into these
mouse models, providing a powerful tool for studying the interactions between
human immune cells and human can
human immune cells
and human can
human cancers.
The company now has an array of fully
human antibodies in its pipeline created with its proprietary VelocImmune
mouse, which has been engineered to express
human antibody genes while still mounting a robust
immune response by making antibodies with fully
human variable regions
and mouse constant regions.
Discuss how
mouse models can be used to study
human immune responses against leukemia (using primary or genetically modified leukemia cells)
and melanoma
As they develop
human clinical trials, Wargo
and colleagues also are conducting lab
and mouse model research to better understand the mechanisms that connect bacteria
and the
immune system.
Using a combination of
human or specially engineered
mouse cells in vitro
and in vivo animal models, study senior investigator Judy Lieberman, MD, PhD; study lead investigator Farokh Dotiwala, PhD, with a team lead by the Brazilian parasitologist Ricardo Gazzinelli, DSc, DVM, found that when an
immune killer cell, such as a T - cell or natural killer (NK) cell, encounters a cell infected with any of three intracellular parasites (Trypanosoma cruzi, Toxoplasma gondii or Leishmania major), it releases three proteins that together kill both the parasite
and the infected cell:
However, chronic liver inflammation in both
mice and humans also led to the accumulation of immunosuppressive lymphocytes, a type of
immune cell Karin
and Shalapour first described two years ago.
Tests in
mice and nonhuman primates had shown TGN1412 to be safe, but when it was injected into
humans — in a dose less than 1/500 of what was given to monkeys — it caused a massive release of infection - fighting T cells that overstimulated the patients»
immune systems, resulting in multiple organ failure.
Cannon used a special strain of
mouse that lacks a functioning
immune system
and so can be given
human immune cells without rejecting them.
A series of biological analyses of the
mice with Tim - 1
and immune cells isolated from
human donors showed that Ebola virus directly binds to T - cells through Tim - 1 protein binding
and causes massive inflammation that thwarts the
immune system.
Because
mice with intact
immune systems are resistant to S. stercoralis infection, the researchers began with an immunocompromised strain of
mice,
and then exposed some to a synthetic steroid called methylprednisolone (MPA) that is commonly used to treat asthma in
humans.
The 1918 virus (r1918) activated many more
mouse genes involved in the
immune system than a modern
human flu virus (Tx91)
and two hybrids between a modern virus
and the 1918 strain.
Looking across evolutionary time
and the genomic landscapes of
humans and mice, an international group of researchers has found powerful clues to why certain processes
and systems in the
mouse — such as the
immune system, metabolism
and stress response — are so different from those in people.
For example, investigators found that for the
mouse immune system, metabolic processes
and stress response, the activity of some genes varied between
mice and humans, which echoes earlier research.
Walford's new research is based on the fact that in
mice and humans, the
immune system malfunctions during aging, losing the ability to distinguish between healthy cells
and invasive pathogens such as bacteria
and viruses.
The findings have implications for all aspects of medical
and scientific research because laboratory
mice underpin studies whose results have a transformative effect on
human and animal lives through vaccination
and other
immune - based therapies.
HIV can not copy itself in
mouse cells, so they purchased
mice that had deliberately crippled
immune systems
and then rebuilt them with
human stem cells.
What's more, the
mice developed symptoms typical of rheumatoid arthritis in
humans: Their joints became inflamed
and were filled with
immune system chemical messengers, such as TNF - α, which make the
immune system turn on the body.
The
mice they studied are engineered to express
human leukocyte antigen, which helps regulate the
human immune system,
and, in this case, helped the
mice produce the powerful T cells again
human cancer.
Researchers will begin by studying the
immune effects of introducing
mouse bacteria,
and then go on to study the effects of introducing
human strains.
Hypothesis driven approaches to vaccinology can utilise the knowledge gained from mechanistic
mouse models
and our molecular understanding of intrinsic defects to
human cells.5 However, caution is required when extrapolating data from murine models, as there are substantial differences between
immune ageing in
mice and humans.6 Nevertheless, model systems
and ex vivo analyses of molecular alterations in aged
human cells have identified multiple changes in the vaccination response with age
and the aged
immune system in general.
Our technological expertise ranges from the most fundamental approaches to study membrane transport in lymphocytes
and dendritic cells (subcellular compartmentalization, intravital microscopy, phagosomal functions), the systematic analysis of gene expression
and it regulation (RNAseq, Chip Seq, proteomics)
and physiological
and pathological
immune responses (
mouse models for cancer immunity, immunomodulation / vaccination,
human clinical studies in cancer).
We chose this model because 1) it more closely recapitulates features of
human pancreatic cancer than do s.c. - implanted tumors, 2) it can be used in immunocompetent
mice to permit assessment of
immune responses,
and 3) the cells grow in vivo with predictable kinetics (34).
«Over the past ten years, several research groups, including our own, have shown the importance of certain
immune cell subsets in preventing or exacerbating heart disease in
mice, but we are just beginning to understand how the metabolism
and function of these
immune cells change during cardiovascular disease progression in
humans,» says Hedrick.
Using studies in both
mice and humans, they found that exposure to farm dust increases expression of a protective protein that suppresses the inflammatory
immune system by modifying the communication between the lining of the lungs
and the
immune system.
Despite the differences,
mice can still be used to study the
immune system
and metabolic processes in
humans.
A recently published paper showed that
mice with colon cancer can be «vaccinated» with
human embryonic stem cells
and have a significant
immune response against the cancer (Li et al., 2009).
For the study, the researchers treated part of a
human artery — a few millimeters in diameter — with the siRNA - loaded nanoparticles
and transplanted it into the abdominal aorta of an
immune - deficient
mouse inoculated with
human T cells.
While earlier work has reported persistence of HIV in these cells — macrophages — investigators in this work developed a
mouse model with an
immune system generated from
human cells but lacking T cells, which are a primary target of
and reservoir for HIV.
In recent years, researchers have developed so - called «senolytic» drugs that wipe out senescent cells in aging
mice and mouse models of age - related disease, exploiting the high dependence of these cells on specific biochemical survival pathways.9, 10 In these studies, senolytic drugs have restored exercise capacity9
and formation of new blood
and immune precursor cells11 in aging
mice to near youthful norms,
and prevented or treated
mouse models of diseases of aging like osteoarthritis, 12 fibrotic lung disease, 13 hair loss, 14 atherosclerosis, 15,16
and age - related diseases of the heart itself.9 UNITY Biotechnology is leading a growing charge toward the clinic, with
human clinical trials expected to begin in 2019.