progenitor cells

Cephalopod eyes are fascinating. Just like us vertebrates they have camera-type eyes, a hollow liquid-filled chamber with an opening, the iris, and a lens through which light enters and is projected onto the photosensitive surface, the retina. Despite their similarities, vertebrate and cephalopod camera-type eyes have different origins and evolved independently. There are some striking differences that highlight this:

Unlike us, the photoreceptor cells of cephalopods point outwards towards the source of the light rather than inwards. This not only means the we have “inverted” retinas, it also means that cephalopods don’t have a blind spot because the nerve fibers that transmit the visual impulses from the retina to the brain collect and exit the eye behind the retina rather than in front of it. The developmental origins of the eye tissues are also different. For instance, in vertebrates the complex layers of the retina develop from nerve tissue, while the lens develops from skin tissue. In cephalopods both tissues develop from progenitor skin cells.

Cephalopods have excellent vision, and use complex visual cues to communicate with each other, camouflage themselves, and send signals to their environment. To do this they use highly adaptible pigment-filled cells in their skin called chromatophores. The capricorn night octopus (Callistoctopus alpheus) in the photo looks blue, but if it would open all its chromatophores it would turn deep red with bright white polka dots.

Photo credit: David Liittschwager, National Geographic.

Clinical Trial Offers Hope to Restore Limb Function in Man with Complete Cervical Spinal Cord Injury

Physicians at Rush University Medical Center became the first in Illinois to inject AST-OPC1 (oligodendrocyte progenitor cells), an experimental treatment, into the damaged cervical spine of a recently paralyzed man as part of a multicenter clinical trial.

Dr. Richard G. Fessler, professor of neurological surgery at Rush University Medical Center, is principal investigator for the Phase 1/2a, multicenter clinical trial involving AST-OPC1 at Rush, one of six centers in the country currently studying this new approach.

Fessler injected an experimental dose of 10 million AST-OPC1 cells directly into the paralyzed man’s cervical spinal cord in mid-August. These injected cells were derived from human embryonic stem cells. They work by supporting the proper functioning of nerve cells, potentially helping to restore the conductivity of signals from the brain to the upper extremities (hands, arms, fingers) in a recently damaged spinal cord.

Interim research results from the trial were announced at the 55th Annual Scientific Meeting of the International Spinal Cord Society (ISCoS), which was held in Vienna, Austria, on September 14-16, 2016.

“Until now, there have been no new treatment options for the 17,000 new spinal cord injuries that happen each year,” says Fessler. “We may be on the verge of making a major breakthrough after decades of attempts.”

The next phase of the clinical research trial will involve a dose of 20 million oligodendrocyte progenitor cells, which is the highest dose being studied in this study involving patients who have recently suffered a complete cervical spinal cord injury.

“These injuries can be devastating, causing both emotional and physical distress, but there is now hope. In the 20 years of my research, we have now reached a new era where we hope to demonstrate through research that a dose of very specially made human cells delivered directly to the injured site can have an impact on motor or sensory function,” says Fessler. “Generating even modest improvements in motor or sensory function can possibly result in significant improvements in quality of life.”

Early research results from the trial were announced at the 55th Annual Scientific Meeting of the International Spinal Cord Society (ISCoS), which is being held in Vienna, Austria, on September 14-16, 2016.

“Our preliminary results show that we may in fact be getting some regeneration. Some of those who have lost use of their hands are starting to get function back. That’s the first time in history that’s ever been done,” says Fessler. “Just as a journey of a thousand miles is done one step at a time, repairing spinal cord injuries is being done one step at a time. And, now, we can say that we’ve taken that first step.”

The clinical trial is designed to assess safety and effectiveness of escalating doses of the special cells (AST-OPC1) in individuals with a complete cervical spinal cord injury. Thus far, three individuals have been enrolled in the study at Rush.
The trial has involved the testing of three escalating doses of AST-OPC1 in patients with subacute, C5-C7, neurologically-complete cervical spinal cord injury. These individuals have essentially lost all sensation and movement below their injury site with severe paralysis of the upper and lower limbs. AST-OPC1 is administered 14 to 30 days post-injury. Patients will be followed by neurological exams and imaging methods to assess the safety and activity of the product.

“In the future, this treatment may potentially be used for peripheral nerve injury or other conditions which affect the spinal cord, such as MS,” says Fessler.

For this therapy to work, the cord has to be in continuity and not severed, according to Fessler. The study seeks male and female patients ages 18 to 65 who recently experienced a complete cervical spinal cord injury at the neck that resulted in tetraplegia, the partial or total paralysis of arms, legs and torso. Patients must be able to start screening within 25 days of their injury, and participate in an elective surgical procedure to inject AST-OPC1 14 to 30 days following injury. Participants also must be able to provide consent and commit to a long-term follow-up study.

The study is funded by Asterias Biotherapeutics, which developed the AST-OPC1 (oligodendrocyte progenitor cells) treatment used in the study, and also in part by a $14.3 million grant from the California Institute for Regenerative Medicine (CIRM).

AST-OPC1 cells are made from embryonic stem cells by carefully converting them into oligodendrocyte progenitor cells (OPCs), which are cells found in the brain and spinal cord that support the healthy functioning of nerve cells. In previous laboratory studies, AST-OPC1 was shown to produce neurotrophic factors, stimulate vascularization and induce remyelination of denuded axons. All are critical factors in the survival, regrowth and conduction of nerve impulses through axons at the injury site, according to Edward D. Wirth III, MD, PhD, chief medical director of Asterias and lead investigator of the study, dubbed “SCiStar.”

My Uworld notes- 6
  • serum sickness is a type 3 HSR characterized by deposition of circulation complement fixing immune complexes and resulting vasculitis. Associated findings include fever, urticaria, arthralgias, glomerulonephritis, lymphadenopathy and a low serum c3 level 5-10 days after intravascular exposure to antigen. type 3 HSR typically activate complement at local site where immune complexes containing IgG and or IgM complement fixing antibodies have been deposited. This often results in hypocomplementemia including decreased C3 level

  • liver dz-a/w AFP

  • carcinoembryonic antigen (CEA) a/w colorectal cancer

  • CA125 -ovarian cancer. Both CEA and ca125 are fr monitoring purposes

  • PSA prostate specific antigen is most useful in establishing extent of prostate cancer and evaluating response to prostate cancer tx.

  • Iced water think cold – cold think cold agglutinins – cold agglutinin associated with infection with mycoplasma pneumonia

  • another cold agglutinin is EBV

  • free air in peritoneal cavity= bowel perforation

  • pancreatic calcification= chronic pancreatitis

  • heavily calcified vessels = atherosclerosis and vascular dz

  • distended bladder= urinary retention

  • air in billiary tract a/w gallstone ileus

  • fluoxetine a/w anorgasmia and decreased libido and increase latency to orgasm. They can however be used to tx premature ejaculation

  • phenelzine= MAO-I used in tx of depression monoamine oxidase is a mitochondrial enzyme that deaminates primary and secondary aromatic amines

  • tricyclic antidepressants can cause orthostatic hypotension example imipramine

  • trazadone- priapism

  • paroxysmal breathlessness and wheezing in young patient unrelated to ingestion of aspirin, pulmonary infection inhaled irritant stress and or exercise should raise a strong suspicion for extrinsic allergic asthma. The granule containing cells in sputum are most likely eosinophils and the crystalloid bodies are most likely Charcot Leyden crystals (contain eosinophil membrane protein)

  • chronic eosinophilic bronchitis in asthmatics involves bronchial wall infiltration by numerous activated eosinophils largely in response to IL5 released by TH2 cells

  • digestion and absorption of nutrients primarily occurs in small intestine. SI cells produce enzymes responsible for nutrient absorption. Proteins in ingested food exist primarily as polypeptides and require hydrolysis to dipeptides tripeptides and amino acid for absorption. Hydrolysis of these polypeptides is accomplished by proteolytic enzymes such as pepsin and trypsin

  • these enzymes are secreted inactive proenzymes trypsinogen and pepsinogen from stomach and pancreas

  • trypsin activates other proteolytics enzymes including chymotrypsin carboxypeptidase and elastase. Activation of trypsinogen to trypsin is achieved by enteropeptidase (or enterokinase)an enzyme produced in duodenum

  • enteropeptidase deficiency results in defective conversion of trypsinogen to active trypsin

  • lipase secreted from exocrine pancreas is the most important enzyme of digestion of triglycerides. Chronc pancreatitis is a painful condition that causes lipase deficiency. This leads to poor fat absorption and steatorrhea

  • secretin is a peptide hormone secreted by S cells of duodenum un response to low duodenal pH. Secretins timulates secretion of bicarbonate from the pancreas and gall bladder and reduces acid secretion in the stomach by reducing production of gastrin. Neutralizing the acidic pH of food entering the duodenum from the stomachis necessary for proper function of pancreatic enzymes (amylase, lipase)

  • trisomy 18 (47XX: Edwards syndrome

    • face: micrognathia, microstomia, eye defects (microphthalmis, cataracts) low set ears and malformed ears prominent occiput

    • CNS: microcephaly, neural tube defects (meningocele, anencephaly), holoprosencephaly, arnold chiri malformation, severe MR delayed psychomotor development

    • musculoskeletal: clenched hands with overlapping fingers (index finger overrides the middle fingerand fifth finger overrides the fourth finger) rocker bottom feet short sternum and hypertonia

    • cardiac: VSD, PDA

    • distinguishing features: clenched hands and or overlapping finger

    • GI: Meckel diverticulum, malrotation

    • ultrasound: intrauterine growth restriction and polyhydramnios especially ina fetus with abnormal hand arrangement

  • unlike patients with Edward’s syndrome neonates with Patau syndrome (trisomy 13) have cleft lip and palate, polydactyly and omphalocele. Patau syndrome is not a/w low set ears and overlapping fingers but do present with rocker bottom feet also

  • 47XXX karyotype is clinically silent however, some affected women have slightly decreased IQ scores. Female newborns with this karyotype are phenotypically normal with no obvious dysmorphism

  • 47XXY Kleinfelter’s syndrome: may be a/w mild mental retardation or normal intelligence. The typical patient is tall mall adult with gynecomastia small testes and infertility. Male newborns with this karyotype are phenotypically normal with no obvious dysmorphism. The clinical findings do not become apparent until adulthood.

  • Sudden onset of abdominal or flank pain hematuria and left sided varicocele together suggests renal vein thrombosis a well known complication of nephrotic syndrome. Nephrotic syndrome is a hypercoagulable state d/t increased loss of anticoagulant factors especially anti thrombinIII (responsible for the thrombotic and thromboembolic complications of nephrotic syndrome)

  • venous drainage from left testes travels throught the left testicular vein into the left renal vein and from there the IVC. In contrast to the right testicular vein which empties directly into the IVC. This difference in venous drinage gives diagnostic significance to left sided varicocele in that it often indicates an occlusion of the left renal vein by a malignant tumour or thrombus

  • malaise low grade fever followed by a facial rash. Feels better now but still has the rash- red flushed cheeks with – clinical presentation of erythema infectiosum aka fifth dz. As the facial rash fades an erythematous rash in reticular lace like pattern often appears on trunk and extremities. The rash of erythema infectiosum is thought to result at lest partly from local immune complex deposition once serum levels of virus specific IgM and IgG have attained high enough levels.

  • Erythema infectiosum= non enveloped DNA virus called parvo B19. The blood group P antigen globoside is a parvovirus B19 is highly tropic for erythrocyte precursors particularly erythrocytes and erythroid progenitor cells

  • Parvo B19 replicates predominantly in the bone marrow

  • anthracyclines daunorubicin doxorubicin epirubicin and idarubicin are chemotherapeutic agents a/w severe cardiotoxicity because of their unique ability to generate free radicals.. Dilated cardiomyopathy is dose dependent and may present months after discontinuation of the drug . Swelling of sarcoplasmic reticulum is the morphologic sign of early stage doxorubicin associated cardiomyopathy. Followed by loss of cardiomyocytes and its symptoms are those of biventricular CHF including dyspnea on exertion orthopnea and peripheral edema

  • dexrazoxane prevents Doxorubicin associated cardiomyopathy because dex is a iron chelating agent that decreases formation of free radicals by anthracyclines.

  • Restrictive cardiomyopathy a/w hemochromatosis amyloidosis sarcoidosis and radiation theraapy : remember -osis

  • hypertrophic cardiomyopathy caused by mutation of beta myosin heavy chain

  • focal cardiomyopathyscarring commonly results in MI

  • pericardial fibrosis usually follows cardiac surgery radiation therapy or viral infections of the pericardium

  • PCP aka angel dust aka phencyclidine commonly associated with violent behaviour

  • LSD can also cause aggressive behaviour but it is more typically characterized by affective liability thought disruption )delusion) and visual hallucination whereas PCP produces more psychomotor agitation including clonic jerking of extremities

  • angel dust can be put on marijuana and smoked LD is ingested orally

  • secobarbital is a street barbiturate a CNS depressant which leads to drowsy drunken state of consciousness without the violent behaviour

  • heroin (opioid) produces CNS psychomotor depression and respiratory depression miosis and bradycardia are common

  • dry tap with no splenomegaly or lymphadenopathy – think aplastic anemia which causes pancytopenia

  • aplastic anemia= hypo cellular bone marrow with fat cells and fibrotic stroma

  • hyper cellular marrow with increased blasts found in myeloproliferative d/o and certain leukemias

  • most common side effect of streptokinase= hemorrhage . Streptokinase is a thrombolytic agent that acts by converting plasminogen to plasmin which subsequently degrades fibrin. It is a foreign protein derived from streptococci and induce HSR.

  • Dissection of ascending aorta manifests as tearing chest pain that radiates to the inter-scapular area commonly occurs in hypertension marfans and ehlers danlos

  • hyperactive jaw jerk reflex when lightly tapped= chvostek’s sign- Hypocalcemic – facial m contraction elicited by tapping facial nerve just anterior to ear. The most common cause of outpatient hypocalcemia is primary hypoparathyroidism which is often d/t prior loss of parathyroid tissue during thyroidectomy

  • scotoma is visual defect that occurs d/t pathologic processes that involve parts of retina or optic nerve resulting in discrete area of altered vision surrounded by zones of normal vision. Lesions of macula cause central scotomas.. examples would include MS, diabetic retinopathy and retinitis pigmentosa

  • verapamil is a calcium channel blocker that slows SA and AV node phase 0 depolarization (in nodal cells, the phase of depolarization is mediated by calcium influx)

  • phase 0 depolarization of cardiac conduction system occurs during diastole thus verapamil slows diastolic depolarization

3

To make an organ or tissue transplant a success, it has to be accepted by the recipients’ immune system and must have good blood supply from a healthy network of small blood vessels. 

For scientists looking to grow tissues in the lab for transplants these are two big obstacles.

But researchers at the University of Bath could help to overcome the problem with a new way of growing tiny blood vessels, like capillaries, from a patient’s own blood.

Their technique uses gel made from blood cells as a scaffold, on which cells that help maintain blood vessel walls, called endothelial progenitor cells (EPCs), are grown. The team has shown that this can grow those essential small blood vessels.

Not only are these tiny blood vessel connections vital for the survival of transplanted tissue, the risk of rejection is lower because the gel and EPCs come from the patient in the first place. 


Images: Tiago Fortunato, University of Bath

Read the research paper

Scientists Uncover Common Cell Signaling Pathway Awry in Some Types of Autism

Brain cells grow faster in children with some forms of autism due to distinct changes in core cell signaling patterns, according to research from the laboratory of Anthony Wynshaw-Boris, MD, PhD, chair of the department of genetics and genome sciences at Case Western Reserve University School of Medicine, and a member of the Case Comprehensive Cancer Center. Rapid cell growth can cause early brain overgrowth, a common feature in 20-30% of autistic children. But, the genetics of autistic children vary making it difficult to pinpoint common mechanisms underlying the disease.

“Autism is a complex disorder with multiple genetic and non-genetic factors,” explained Wynshaw-Boris. “Because the causes are diverse, it may help to define a subset of patients that have a common [symptom], in this case early brain overgrowth.”

In a study published in Molecular Psychiatry, Wynshaw-Boris and his colleagues started with skin cell samples from autistic children with enlarged brains and worked backward. Researchers in the laboratory “reprogrammed” donated skin cells to produce cells found in the developing brain including induced pluripotent stem cells and neural progenitor cells. Stem and progenitor cells are important therapeutic tools as they have the potential to grow into a multitude of cell types. The researchers hypothesized that even though the children in the study had different forms of autism, the precursor cells could be used to find common molecular and cellular mechanisms.

The researchers discovered that cells derived from autistic donors grew faster than those from control subjects and activated their genes in distinct patterns. Genes related to cell growth were unusually active, leading to more cells but fewer connections between them. This can cause faulty cell networks unable to properly transmit signals in the brain and enlarged heads during early development.

The researchers identified abnormal genes in the cells grown from autistic donors as belonging to the Wnt signaling pathway. The Wnt genes are critical for cell growth and serve as central players in cell networks, interfacing with multiple signaling pathways. Wynshaw-Boris previously identified the Wnt pathway as related to autism in mouse models of the disease. In a separate study published in Molecular Psychiatry earlier this year, the Wynshaw-Boris laboratory showed mice lacking Wnt genes display autism-like symptoms including social anxiety and repetitive behavior. The researchers could prevent these adult symptoms by treating the mice with medications that activate Wnt signaling in the uterus, during development.

“The Wnt pathway is one of the core developmental pathways conserved from invertebrates to humans. Our studies solidify previous suggestions that this pathway has a role in autism,” said Wynshaw-Boris.

Once they identified the dysfunctional signaling pathway in their reprogrammed autistic samples, the researchers (including the laboratories of Alysson Muotri, PhD at the University of California San Diego and Fred Gage, PhD at the Salk Institute) attempted to correct it by exposing mature nerve cells derived from autistic donors to drug compounds. One drug currently being tested in clinical trials for autism is insulin growth factor 1 (IGF-1). When the researchers added IGF-1 to nerve cells derived from autistic donors, neural networks were reestablished. It is unclear whether the positive effects of IGF-1 were on the Wnt pathway, and the exact compensatory mechanism requires further investigation.

Wynshaw-Boris’s studies in cell culture and mouse models of autism confirm improper Wnt signaling can lead to rapid brain cell growth and brain enlargement in the embryo, resulting in abnormal social behavior after birth. The next step will be to determine which genes are most impacted by Wnt signaling defects during early development, and how these changes result in abnormal behavior. “We would also like to find other drugs or compounds that may slow down the growth of the cells in tissue culture,” said Wynshaw-Boris. Together, these findings may help researchers unravel common ways brain cells can become impaired during early development in carefully chosen subsets of patients and contribute to symptoms across the autism spectrum.

2

Stem Cells Grow Mini-Kidney

Scientists have coaxed human stem cells to grow different structures found inside working kidneys. The advance is being called an important step toward the goal of growing functional organs from patients’ stem cells once their own kidneys fail.

A research team in Australia and The Netherlands report today in the journal Nature that they were able to grow tiny kidney-like organoids with a complex of different kidney cell types. Over the course of 20 days, the cultured cells differentiated and grew into an organoid containing 500 kidney cells known as nephrons. That substantial number is equal to the state of a more than 14-day-old mouse embryo’s kidney, write Minoru Takasato and colleagues. Comparing the engineered tissue to normal human development, they found its gene expression most closely resembled that of a first-trimester fetal kidney.

“There is a long way to go until clinically useful transplantable kidneys can be engineered, but Takasato and colleagues’ protocol is a valuable step in the right direction,” writes the University of Edinburgh’s Jamie Davies, who did not participate in the research.

Keep reading

Drugs stimulate body’s own stem cells to replace the brain cells lost in multiple sclerosis

A pair of topical medicines already alleviating skin conditions each may prove to have another, even more compelling use: instructing stem cells in the brain to reverse damage caused by multiple sclerosis.

Led by researchers at Case Western Reserve, a multi-institutional team used a new discovery approach to identify drugs that could activate mouse and human brain stem cells in the laboratory. The two most potent drugs – one that currently treats athlete’s foot, and the other, eczema – were capable of stimulating the regeneration of damaged brain cells and reversing paralysis when administered systemically to animal models of multiple sclerosis. The results are published online Monday, April 20, in the scientific journal Nature.

“We know that there are stem cells throughout the adult nervous system that are capable of repairing the damage caused by multiple sclerosis, but until now, we had no way to direct them to act,” said Paul Tesar, PhD, the Dr. Donald and Ruth Weber Goodman Professor of Innovative Therapeutics, and associate professor in the Department of Genetics & Genome Sciences at the Case Western Reserve School of Medicine. “Our approach was to find drugs that could catalyze the body’s own stem cells to replace the cells lost in multiple sclerosis.”

The findings mark the most promising developments to date in efforts to help the millions of people around the world who suffer from multiple sclerosis. The disease is the most common chronic neurological disorder among young adults, and results from aberrant immune cells destroying the protective coating, called myelin, around nerve cells in the brain and spinal cord.

Without myelin, neural signals cannot be transmitted properly along nerves; over time, a patient’s ability to walk, hold a cup or even see is inexorably eroded. Current multiple sclerosis therapies aim to slow further myelin destruction by the immune system, but the Case Western Reserve team used a new approach to create new myelin within the nervous system. Their work offers great promise of developing therapies that reverse disabilities caused by multiple sclerosis or similar neurological disorders.

“To replace damaged cells, much of the stem cell field has focused on direct transplantation of stem cell-derived tissues for regenerative medicine, and that approach is likely to provide enormous benefit down the road,” said Tesar, also a New York Stem Cell Foundation Robertson Investigator and member of the National Center for Regenerative Medicine. “But here we asked if we could find a faster and less invasive approach by using drugs to activate native stem cells already in the adult nervous system and direct them to form new myelin. Our ultimate goal was to enhance the body’s ability to repair itself.”

Tesar emphasized that much work remains before multiple sclerosis patients might benefit from the promising approach. Scientists still must find ways to transform the topical medications for internal use and determine their long-term efficacy and potential side effects. That said, using existing, federally approved drugs enhances the likelihood that the compounds can be made safe for human use.

Tesar and his colleagues could zero in on the two catalyzing medications only because of a breakthrough that his laboratory achieved in 2011. Specifically, the researchers developed a unique process to create massive quantities of a special type of stem cell called an oligodendrocyte progenitor cell (OPC). These OPCs are normally found throughout the adult brain and spinal cord, and therefore inaccessible to study. But once Tesar and his team could produce billions of the OPCs with relative ease, they could begin to test different existing drug formulations to determine which, if any, induced the OPCs to form new myelinating cells.

Using a state-of-the-art imaging microscope, the investigators quantified the effects of 727 previously known drugs, all of which have a history of use in patients, on OPCs in the laboratory. The most promising medications fell into two specific chemical classes. From there, the researchers found that miconazole and clobetasol performed best within the respective classes. Miconazole is found in an array of over-the-counter antifungal lotions and powders, including those to treat athlete’s foot. Clobetasol, meanwhile, is typically available by prescription to treat scalp and other skin conditions such as dermatitis. Neither had been previously considered as a therapeutic for multiple sclerosis, but testing revealed each had an ability to stimulate OPCs to form new myelinating cells. When administered systemically to lab mice afflicted with a multiple sclerosis-like disease, both drugs prompted native OPCs to regenerate new myelin.

“It was a striking reversal of disease severity in the mice,” said Robert Miller, PhD, a member of the neurosciences faculty at Case Western Reserve who, with Tesar, is a co-senior author of the Nature paper. The two collaborated on this project while Miller also served as Vice President for Research at Case Western Reserve; since June his primary appointments are at the George Washington University School of Medicine and Health Sciences, where he is Senior Associate Dean for Research and Vivian Gill Distinguished Research Chair. “The drugs that we identified are able to enhance the regenerative capacity of stem cells in the adult nervous system. This truly represents a paradigm shift in how we think about restoring function to multiple sclerosis patients.”

While the drugs proved to have extraordinary effects on mice, their impact on human patients will not be known fully until actual clinical trials. Nevertheless, Tesar and his team already have added reason for optimism; in addition to the tests with animal cells, they also tested the drugs on human stem cells – and saw the medication prompt a similar response as seen in the mouse cells. Both medications worked well, with miconazole demonstrating the more potent effects.

“We have pioneered technologies that enable us to generate both mouse and human OPCs in our laboratory,” said Fadi Najm, MBA, the first author of the study and Research Scientist in the Department of Genetics & Genome Sciences at the Case Western Reserve School of Medicine. “This uniquely positioned us to test if these drugs could also stimulate human OPCs to generate new myelinating cells.”

Tesar, who recently received the 2015 International Society for Stem Cell Research Outstanding Young Investigator Award, said investigators next will work to deepen their understanding of the mechanism by which these drugs act. Once these details are clear, researchers will modify the drugs to increase their effectiveness in people.

The team is enthusiastic that optimized versions of these two drugs can be advanced to clinical testing for multiple sclerosis in the future, but Tesar emphasized the danger of trying to use current versions for systemic human administration.

“We appreciate that some patients or their families feel they cannot wait for the development of specific approved medications,” Tesar said, “but off-label use of the current forms of these drugs is more likely to increase other health concerns than alleviate multiple sclerosis symptoms. We are working tirelessly to ready a safe and effective drug for clinical use.”

washingtonpost.com
Zika can infect adult brain cells, not just fetal cells, study suggests
A study in mice suggests that Zika virus could damage brain areas responsible for learning and memory.

The more researchers learn about the Zika virus, the worse it seems.

A growing body of research has established that the virus can cause severe birth defects — most notably microcephaly, a condition characterized by an abnormally small head and often incomplete brain development. The virus also has been linked to cases of Guillain-Barre syndrome in adults, a rare autoimmune disorder that can result in paralysis and even death.

Now, in a study in mice, researchers have found evidence that suggests adult brain cells critical to learning and memory also might be susceptible to the Zika virus.

“This was kind of a surprise,” Joseph Gleeson, a professor at Rockefeller University and one of the co-authors of the study published Thursday in the journal Cell Stem Cell, said in an interview. “We think of Zika health concerns being limited mostly to pregnant women.”

[For Zika-infected pregnancies, microcephaly risk may be as high as 13 percent]

In a developing fetus, the brain is made primarily of “neural progenitor” cells, a type of stem cell. Researchers believe these cells are especially susceptible to infection by the Zika virus, which can hinder their development and disrupt brain growth. Most adult neurons are believed to be resistant to Zika, which could explain why adults seem less at risk from the virus’s most devastating effects.

But some neural progenitor cells remain in adults, where they replenish the brain’s neurons over the course of a lifetime. These pockets of stem cells are vital for learning and memory. Gleeson and his colleagues suspected that if Zika can infect fetal neural progenitor cells, the virus might have the same ability to infect adult neural progenitor cells. That’s precisely what they found.

“We asked whether [these cells] were vulnerable to Zika in the same way the fetal brain is,” Glesson said. “The answer is definitely yes.”

Gleeson is the first to admit that the findings represent only an initial step in discovering whether Zika can endanger adult human brain cells. For starters, the study was conducted only in mice, and only at a single point in time. More research will be necessary to see whether the results of the mouse model translates to humans, and whether the damage to adult brain cells can cause long-term neurological damage or affect behavior.

But the initial findings suggest that the Zika virus, which has spread to the United States and more than 60 other countries over the past year, may not be as innocuous as it seems for adults, most of whom never realize they have been infected. Researchers found that infected mice had more cell death in their brains and reduced generation of new neurons, which is key to learning and memory. The possible consequences of damaged neural progenitor cells in humans would include cognitive problems and a higher likelihood for conditions such as depression and Alzheimer’s disease.

[Obama administration to shift $81 million to fight Zika]

“Zika can clearly enter the brain of adults and can wreak havoc,” Sujan Shresta, another study co-author and a professor at the La Jolla Institute of Allergy and Immunology, said in a statement. “But it’s a complex disease — it’s catastrophic for early brain development, yet the majority of adults who are infected with Zika rarely show detectable symptoms. Its effect on the adult brain may be more subtle, and now we know what to look for.”

William Schaffner, an infectious disease expert at Vanderbilt University Medical Center, agreed Thursday that the findings are preliminary. But he also called it troubling.

“Here’s the deal — the more we’ve learned about the Zika virus, the nastier it is,” said Schaffner, who was not involved in the study. He said scientists have had concerns all along about Zika’s ability to damage the brain, but until now the worries have focused mostly on the developing brain. “This mouse study will increase our anxiety. … It’s an additional potential way that this virus can cause human illness.”

That’s a possibility that demands further examination, he said, given the hundreds of thousands of people already infected by Zika — a number that continues to grow daily.

“Our attention, quite understandably, has been devoted to pregnant women and newborns, and preventing those infections,” Schaffner said. “This mouse study will tell investigators that, in addition to pregnant women, you have to establish some studies in older children and adults as well.”

Gleeson agreed. “We don’t want to have this be a panic. Zika, for the most part, is a benign condition in healthy humans,” he said. “But we also need to look at the potential consequences in a careful way.”

Researchers observe stem cell specialization in the brain

Adult stem cells are flexible and can transform themselves into a wide variety of special cell types. Because they are harvested from adult organisms, there are no ethical objections to their use, and they therefore open up major possibilities in biomedicine. For instance, adult stem cells enable the stabilization or even regeneration of damaged tissue. Neural stem cells form a reservoir for nerve cells. Researchers hope to use them to treat neurodegenerative disorders such as Parkinson’s and Alzheimer’s disease. Tübingen researchers led by Professor Olga Garaschuk of the University of Tübingen’s Institute for Physiology, working with colleagues from Yale University, the Max Planck Institute of Neurobiology in Martinsried and the Helmholtz Center in Munich, studied the integration of these cells into the pre-existing neural network in the living organism. The results of their study have been published in the latest edition of Nature Communications.

There are only two places in the brains of adult mammals where stem cells can be found – the lateral ventricles and the hippocampus. These stem cells are generating neurons throughout life. The researchers focused on a stem cell zone in the lateral ventricle, from where progenitors of the nerve cells migrate towards the olfactory bulb. The olfactory nerves which start in the nasal tissue run down to this structure, which in mice is located at the frontal base of the brain. It is there that the former stem cells specialized in the task of processing information on smells detected by the nose. “Using the latest methods in microscopy, we were for the first time able to directly monitor functional properties of migrating neural progenitor cells inside the olfactory bulb in mice,” says Olga Garaschuk. The researchers were able to track the cells using special fluorescent markers whose intensity changes according to the cell’s activity.

The study showed that as little as 48 hours after the cells had arrived in the olfactory bulb, around half of them were capable of responding to olfactory stimuli. Even though the neural progenitor cells were still migrating, their sensitivity to odorants and their electrical activity were similar to those of the surrounding, mature neurons. The mature pattern of odor-evoked responses of these cells strongly contrasted with their molecular phenotype which was typical of immature, migrating neuroblasts. “Our data reveal a remarkably rapid functional integration of adult-born cells into the pre-existing neural network,” says Garaschuk, “and they show that sensory-driven activity is in a position to orchestrate their migration and differentiation as well as their decision of when and where to integrate.”

OB Science Time: Saving Cosima

So we are all very worried about our geek monkey and her mysterious illness! And many people have questions about how exactly Cosima can be saved, so I thought I’d help out!

So we know from the Cophine autopsy scene that this is an unknown immunological disease. This means that the problem is in the cells of the immune system. But what exactly are these cells?

A major player here is the T cell. T cells are cells of the immune system that can attack foreign bodies within the cells, to prevent you from getting sick. There are multiple kinds of T cells, including the cells that destroy tumor cells, like those that are found in the sick clones. There are tons of other cells in the immune system, but for the sake of clarity here, I will be focused on the T cells.

So the formation of T cells happens as part of the following pathway: stem cell -> lymphoid stem cell -> T cell progenitor -> specific T cell. The cell is set on this pathway beginning with rapid cell division, and then the expression of specific markers that cause the cell to differentiate into a T cell from a stem cell. This process begins in the bone marrow, where the stem cells are found, and then the cells move to the Thymus, an organ of the immune system located in the chest between the lungs.

So, back to Orphan Black. It would seem that the clone disease is a problem with the T cells that are supposed to fight off tumor growth. The T cells are defective, and now tumors are growing freely.

The best way to try to fix this (outside of gene therapy, which is the solution Ethan holds) is via a bone marrow transplant. The new bone marrow will have stem cells that are hopefully not comprised, and they can form new T cells that can successfully stop tumor growth, bringing our babies back to good health.

We can’t use bone marrow from the other clones because those stem cells are most likely compromised as well (maybe not in Sarah/Helena but it’s not a safe bet). We can’t use some random bone marrow, because you need to match blood type, and other markers to make sure the transplant is viable in the clones and isn’t rejected. So Kira is the best bet because she shares DNA with the clones so she is compatible, but doesn’t share all the same information, so there’s more chance of success!

Now, another solution could be Helena’s “babies”. At this point in development, these “babies” are basically just balls of stem cells. The cells have yet to differentiate into cells of specific tissues, so they all have the ability to become any type of cell. Helena could save the day by giving her “babies” up to help fight the disease!

So that’s a little bit about the science behind this all. I hope that helped you guys out! :D (and SAVE COSIMA!!!)