Category Archives: California Stem Cells

The presence of neurotransmitters in the gut is why its sometimes described as the second brain. Scientists have long known that there is cross-talk between the gut and our first brain, the central nervous system, but exactly how that communication plays out was a mystery.

Scientists finally have a better idea why certain meals send you running for the bathroom, a discovery that provides insight into the connection between your gut and brain and may point toward new therapies for intestinal disorders such as irritable bowel syndrome (IBS).

The team behind this is led by Holly Ingraham and David Julius of the University of California at San Francisco. Theyre also married, but until a few years ago, their relationship was strictly personal. Ingraham studies female metabolism, while Julius focuses on the brains response to pain. The divergent fields seemed to leave little room for collaboration until scientists in Juliuss lab made a surprising observation: Painful spider venom activates proteins in the gut.

The gut epithelium, which is the thin tissue lining that cavity, is a unique entity. Spread out all its folds and crevices and you could cover a studio apartment one that would teem with microbes, microbial signaling molecules, food byproducts and hormones. One hormone, serotonin, is a neurotransmitter that affects mood, sleep, sex drive and bowel movements. It is produced mainly by specialized enterochromaffin cells (EC), whichs make up less than 1 percent of the gut epithelium collectively, only a small end table in that studio apartment but they excrete more than 90 percent of the serotonin.

The presence of neurotransmitters in the gut is why its sometimes described as the second brain. Scientists have long known there is cross-talk between the gut and our first brain, the central nervous system, but exactly how that communication plays out has been a mystery.

Nicholas Bellono, a scientist in Julius lab, wanted to find out what neurotransmitters such as serotonin are doing in the gut, so Julius and Ingraham introduced him to James Bayrer, a gastroenterologist working in Ingrahams lab. Together, they and their collaborators in Australia co-wrote a study published Thursday in the journal Cell that demonstrates how EC cells translate chemical signals into neurological ones.

To do this, the team used mouse organoids basically, organs in a dish. The researchers isolated intestinal stem cells and used them to grow 3D mini-guts. They challenged the mini-guts with different stimuli and measured the resulting electrical responses. The method produced a very elegant model, noted Diego Bohorquez, assistant professor of medicine and neurology at Duke University, who was not involved in the research.

Gut epithelial cells are known to respond to mechanical stimulation; thats how our stomach signals its full. But the researchers found that even a light touch with certain compounds triggered an intense reaction. The EC cells were especially sensitive to adrenaline and the chemicals that give wasabi and horseradish their strong flavor. Plants in the mustard family evolved these compounds to protect themselves from insects. Our gut perceives them as a danger, causing inflammation.

To figure out the consequences of aggravating EC cells, the researchers used mice in which the cells were tagged with fluorescent molecules. They found EC cells contain receptors that recognize adrenaline, spicy food compounds and foul smells such as sweaty socks or stinky cheese. They then showed that these cells form associations with nerve fibers and produce compounds that are a hallmark of synapses the connections between nerves. When challenged with adrenaline-like compounds, the EC cells became electrically charged, and that produced a rush of serotonin that activated the nearby nerve fiber.

Bohorquez called this discovery an important step forward because it demonstrates what scientists have long suspected: Chemical stimulants electrically excite cells lining the gut, which then directly communicate with nerve cells.

There is really a gut skin cell that sits there and fires action potential like a nerve cell, said Arthur Beyder, who studies EC cells at the Mayo Clinic. Its like a Morse code. ... Theyre communicating.

The fact these cells are activated by adrenaline means the brain is in touch with the gut, as well, but we dont know why. It could be communicating with the microbiome, Beyder suggested.

These EC cells appear to specifically recognize compounds that could serve as a threat or reflect injury.

So youve got the central nervous system and the gut brain. Sometimes they talk, and sometimes they argue, and you get these gut pains, Bayrer explained. When EC cells detect an irritant, they speed up our bowels to get rid of the offender.

Ingraham noted intestinal disorders are becoming more common, especially as people age.

We dont like to talk about these issues, but constipation and diarrhea are seriously debilitating, she said.

EC cells are probably hypersensitive in people with irritable bowel syndrome. Patients often complain of discomfort or irritation, but there is not a measurable amount of inflammation. Greater understanding of normal epithelial cell activities could improve the diagnosis of IBS, Bayrer said.

Bohorquez suggested follow-up research could lead to new drugs to block EC receptors or even the use of electrical devices to minimize EC activity. An important next step will be determining if EC cells also affect the immune system, because immune cells cruise along underneath epithelial cells, Bayrer added.

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Study may shed light on intestinal disorders - The News Herald

DJuan Farmer grew up in a neighborhood where attending college let alone pursuing a PhD or postdoctoral training was not the expectation.

How did he do it?

Will power, said Farmer, who is pursuing his postdoctoral training in the USC Stem Cell laboratory of Gage Crump.

Growing up in Compton, Farmer became intrigued by medicine and science after reading the memoir Death Be Not Proud by John Gunther. The book chronicles the life of Gunthers son, a budding scientist who died of a brain tumor at age 17.

One of my older brothers got that book for some reason from his school as in he had to do a report, and he never read it, Farmer said. So I read it and I still have it. I had to be in my early teens maybe 12, 13. And I said, I want to be a doctor or an oncologist.

Soon afterward, Farmer earned admission into a highly competitive magnet high school: the California Academy of Mathematics and Science on the campus of California State University, Dominguez Hills.

Farmer became the first person in his family to attend college and set an example followed by his two younger brothers. As a UCLA undergraduate pursuing his bachelor of science in molecular, cell and developmental biology, Farmer discovered his passion for research in a roundabout way.

I went to UCLA at a time where there were only 100 African-Americans in the class that year, so there was a lot of advocacy and discussion about it, said Farmer, whose first research experience looked at perceived discrimination or perceived stress and how the body responds to it. But I discovered that I was more interested in how the biology worked, he said.

Inspired by this curiosity, Farmer joined the laboratory of Luisa Iruela-Arispe, where he studied the role of estrogen signaling in early mouse placental development.

When I saw Dr. Iruela-Arispes work, I fell in love, and I was in the laboratory more than I should have been in terms of balance and everything else, Farmer said. So very quickly, I knew I wanted to do a PhD. I didnt want to do medicine anymore.

To ensure that he would enjoy even longer hours in the lab, he did a one-year post-baccalaureate fellowship at the National Institutes of Health. In the lab of Lawrence Brody, Farmer studied genetic variations that affect the metabolism of Vitamin B12 and resulting birth defects in the heart and brain.

I loved it there, he said. That was a really strong indicator that Id be happy as a graduate student, and I was.

As a PhD candidate in biochemistry and molecular biology, he joined the lab of Michael McManus at the University of California, San Francisco. Farmer studied the role of molecules called microRNAs in the development of the lacrimal glands that produce tears and lubricate the eyes. Without lacrimal glands, an animals vision can be drastically impaired.

Farmer has earned the inaugural Choi Family Postdoctoral Fellowship, which provides support to recruit exceptional postdoctoral fellows to USC Stem Cell labs.

In his new position, Farmer is looking forward to shifting his focus to craniofacial and skeletal development in the Crump Laboratory at USC. He will contribute to the effort to understand a serious birth defect known as craniosynostosis, which can constrict and damage the developing brain due to the premature fusion of joints in the skull called sutures.

What Im really interested in is how early defects in cellular identity and behavior lead to late onset defects.

DJuan Farmer

What Im really interested in is how early defects in cellular identity and behavior lead to late onset defects, Farmer said. What early changes lead to the premature fusion of sutures and can these cells be recovered? People often assume that if you correct the mutated gene, its going to correct the defect. Yet in some processes, it might be too late, and intervention might need to be really early.

Farmer is grateful to the Choi Family for its support of this important research and of his scientific training. Looking ahead, he aspires to become an investigator running his own lab at a university.

Its definitely the dream, he said. And being involved in both minority and first-generation activities is, in part, why I really like the idea of being in the academic setting. Its great to be a mentor and improve the education system while doing science.

More stories about: First-Generation Students, Stem Cells

USCs Joint Educational Project introduces fourth- and fifth-graders to virtual reality, 3-D printing and drones.

By studying zebrafish, Joanna Smeeton seeks ways to treat a persons aversion to cold and pain.

The gift will support early-stage research projects at three California university stem cell centers, including USCs.

Middle and high school students visit labs and tour USCs stem cell research center,cancer center and Keck Hospital of USC.

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Stem cell scientist defies expectations through sheer determination - USC News

In a world first, surgeons in the Chinese city of Zhengzhou are planning to inject stem cells derived from human embryos into the brains of patients with Parkinson's disease with the aim of treating their debilitating symptoms.

Meanwhile, another medical team in the same city is aiming to target vision loss using embryonic stem cells (ESC) to replace lost cells in the retina, marking a new direction in China in the wake of major changes in how the country regulates stem cell treatments.

While similar treatments on Parkinson's patients have already been tested in Australia, those trials relied on cells taken from eggs that were forced to divide without first being fertilised in an effort to circumvent any ethical concerns.

Stem cells are a little like blank slates that are yet to take on a specific task. If you rewind the clock on any of your body's tissues, its cells will become less specialised, until you're left with a cell with a lot of potential to become nearly anything.

In the case of both kinds of embryonic stem cells, divided egg cells are subjected to various treatments to encourage them to develop into replacement cells that could treat a condition in a recipient.

The symptoms of Parkinson's disease are largely caused by a loss of nervous tissue deep inside the brain in an area called the basal ganglia.

Losing those cells means a loss of a neurotransmitter called dopamine, and with it a lower ability to control nervous impulses that would prevent muscles in the extremities from activating.

In the case of a condition called macular degeneration, damage to a layer of tissue called the retinal pigment epithelium at the back of the eye causes the light-catching cells above it to die.

By turning ESC into cells that can naturally develop into the tissues that have deteriorated such as the precursors to neurons that can produce dopamine, or into retinal tissue and then injecting it into the target site, the researchers hope to improve the lost functions.

Not everybody is convinced of the success of trials such as those being done in China and last year in Australia.

A stem cell biologist from the Scripps Research Institute in California, Jeanne Loring, believes the choice of cell used in both Parkinson's disease trials won't be specialised enough to match expected results.

"Not knowing what the cells will become is troubling," Loring told David Cyranoski at Nature.

But the research team in China remains confident in its decision.

Qi Zhou from the Chinese Academy of Sciences Institute of Zoology in Beijing is the stem cell specialist leading both sets of ESC trials, and says four years of animal trials conducted on monkeys have so far showed promising results.

"We have all the imaging data, behavioural data, and molecular data to support efficacy," Zhou told Nature.

He also claims the team conducting the Parkinson's trial have been selective with their potential candidates, choosing patients who will have the least chance of rejecting the ESCs from the cell bank.

In 2015, China introduced tough new regulations to deal with the growing problem of 'rogue clinics' offering stem cell treatments without due record keeping or process, making it hard to evaluate safety, or even the types of cells used in the treatments.

The changes are set to improve the ethics and safety of stem cell treatments by enforcing the use of cells through a regulatory body, ensuring informed patient consent, and permitting treatments only through authorised hospitals.

Time will tell if the regulations can be enforced, but for stem cell researchers, the changes are positive.

"It will be a major new direction for China," stem cell scientist Pei Xuetaotold Nature.

If the results are as good as the teams in Australia and China predict, it could also set new standards for the world.

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World-first trials have been launched to treat Parkinson's and ... - ScienceAlert

In experiments in mice, UC San Francisco researchers have discovered that regulatory T cells (Tregs; pronounced tee-regs), a type of immune cell generally associated with controlling inflammation,directly trigger stem cells in the skin to promote healthy hair growth. Without these immune cells as partners, the researchers found, the stem cells cannot regenerate hair follicles, leading to baldness.

Our hair follicles are constantly recycling: when a hair falls out, a portion of the hair follicle has to grow back, saidMichael Rosenblum, M.D., an assistant professor of dermatology at UCSF and senior author on the new paper. This has been thought to be an entirely stem cell-dependent process, but it turns out Tregs are essential. If you knock out this one immune cell type, hair just doesnt grow.

The new study published online May 26 inCell suggests that defects in Tregs could be responsible for alopecia areata, a common autoimmune disorder that causes hair loss, and could potentially play a role in other forms of baldness, including male pattern baldness, Rosenblum said. Since the same stem cells are responsible for helping heal the skin after injury, the study raises the possibility that Tregs may play a key role in wound repair as well.

Normally Tregs act as peacekeepers and diplomats, informing the rest of the immune system of the difference between friend and foe. When Tregs dont function properly, we may develop allergies to harmless substances like peanut protein or cat dander, or suffer from autoimmune disorders in which the immune system turns on the bodys own tissues.

Like other immune cells, most Tregs reside in the bodys lymph nodes, but some live permanently in other tissues, where they seem to have evolved to assist with local metabolic functions as well as playing their normal anti-inflammatory role. In the skin, for example, Rosenblum and colleagues have previously shown that Tregs help establish immune tolerance to healthy skin microbes in newborn mice, and these cells also secrete molecules that help with wound healing into adulthood.

Rosenblum, who is both an immunologist and a dermatologist, wanted to better understand the role of these resident immune cells in skin health. To do this, he and his team developed a technique for temporarily removing Tregs from the skin. But when they shaved patches of hair from these mice to make observations of the affected skin, they made a surprising discovery. We quickly noticed that the shaved patches of hair never grew back, and we thought, Hmm, now thats interesting, Rosenblum said. We realized we had to delve into this further.

In the new research, led by UCSF postdoctoral fellow and first authorNiwa Ali,several lines of evidence suggested that Tregs play a role in triggering hair follicle regeneration.

First, imaging experiments revealed that Tregs have a close relationship with the stem cells that reside within hair follicles and allow them to regenerate: the number of active Tregs clustering around follicle stem cells typically swells by three-fold as follicles enter the growth phase of their regular cycle of rest and regeneration. Also, removing Tregs from the skin blocked hair regrowth only if this was done within the first three days after shaving a patch of skin, when follicle regeneration would normally be activated. Getting rid of Tregs later on, once the regeneration had already begun, had no effect on hair regrowth.

Tregs role in triggering hair growth did not appear related to their normal ability to tamp down tissue inflammation, the researchers found. Instead, they discovered that Tregs trigger stem cell activation directly through a common cell-cell communication system known as the Notch pathway. First, the team demonstrated that Tregs in the skin express unusually high levels of a Notch signaling protein called Jagged 1 (Jag1), compared to Tregs elsewhere in the body. They then showed that removing Tregs from the skin significantly reduced Notch signaling in follicle stem cells, and that replacing Tregs with microscopic beads covered in Jag1 protein restored Notch signaling in the stem cells and successfully activated follicle regeneration.

Its as if the skin stem cells and Tregs have co-evolved, so that the Tregs not only guard the stem cells against inflammation but also take part in their regenerative work, Rosenblum said. Now the stem cells rely on the Tregs completely to know when its time to start regenerating.

Rosenblum said the findings may have implications for alopecia areata, an autoimmune disease that interferes with hair follicle regeneration and causes patients to lose hair in patches from their scalp, eyebrows, and faces. Alopecia is among the most common human autoimmune diseases its as common as rheumatoid arthritis, and more common than type 1 diabetes but scientists have little idea what causes it.

After his team first observed hair loss in Treg-deficient mice, Rosenblum learned that the genes associated with alopecia in previous studies are almost all related to Tregs, and treatments that boost Treg function have been shown to be an effective treatment for the disease. Rosenblum speculates that better understanding Tregs critical role in hair growth could lead to improved treatments for hair loss more generally.

The study also adds to a growing sense that immune cells play much broader roles in tissue biology than had previously been appreciated, said Rosenblum, who plans to explore whether Tregs in the skin also play a role in wound healing, since the same follicle stem cells are involved in regenerating skin following injury.

We think of immune cells as coming into a tissue to fight infection, while stem cells are there to regenerate the tissue after its damaged, he said. But what we found here is that stem cells and immune cells have to work together to make regeneration possible.

Niwa Aliof UCSF was the lead author on the new study. Additional authors were Bahar Zirak,Robert Sanchez Rodriguez, Mariela L. Pauli,Hong-An Truong, Kevin Lai,Richard Ahn, Kaitlin Corbin, Margaret M. Lowe, PharmD,Tiffany C. Scharschmidt, M.D., Keyon Taravati, Madeleine R. Tan,Roberto R. Ricardo-Gonzalez, M.D., Audrey Nosbaum, M.D.,Wilson Liao, M.D., andAbul K. Abbas, MBBS, of UCSF; Frank O. Nestle, M.D., of Kings College London; Marta Bertoliniand Ralf Paus, M.D., of the University of Mnster in Germany; and George Cotsarelis, M.D., of the University of Pennsylvanias Perelman School of Medicine.

The work was primarily supported by the U.S. National Institutes of Health (K08-AR062064, DP2-AR068130, R21-AR066821), the Burroughs Wellcome Fund, a Scleroderma Research Foundation grant, the National Psoriasis Foundation and the Dermatology Foundation.

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A new baldness treatment? - University of California

For the first time, scientists have discovered that a common type of immune cell directly triggers stem cells in the skin that are responsible for hair growth in mice. Without this trigger, hair follicles just don't do their job -even if they have the stem cells necessary to proceed.

As the mechanisms for hair growth in mice are similar in humans, the researchers hope their newly uncovered mechanism could lead to a better understanding of conditions like alopecia, and other types of baldness.

Among the various immune system players we have in the body, there's a subclass of immune cells called regulatory T cells, or Tregs for short.

The vast majority of Tregs live in our lymph nodes, where they help to control inflammation throughout the body. But we also have subsets of Tregs that reside in other body parts, such as muscle or lung tissue.

And studies are starting to show that these 'tissue-resident' Tregs may be performing unique roles specific to the part of body they're in.

Researchers know that both mice and humans have a lot of Tregs in the skin, but so far we know very little about their function there.

Seeing that skin-specific Tregs tend to sit around hair follicles, a team led by researchers from the University of California San Francisco (UCSF) investigated the hypothesis that these immune cells were somehow involved in hair growth.

What they discovered is not just involvement, but a direct trigger - making Tregs a super-important part of the hair growth process.

"Our hair follicles are constantly recycling: when a hair falls out, a portion of the hair follicle has to grow back," senior researcher Michael Rosenblum said in a press statement.

"This has been thought to be an entirely stem cell-dependent process, but it turns out Tregs are essential."

In mammals, hair follicles regenerate in a specific pattern, cycling between growth phases (known as anagen) and rest phases (telogen).

The team tracked the amount of Tregs in the skin of mice during these different phases of hair growth, and found a tight correlation - in the telogen phase these immune cells were much more abundant.

What's more, highly active Tregs were crowding around hair follicles at three times the normal rate, right towards the end of the hair growth rest phase.

Intrigued by this correlation, the scientists took a step further to uncover the biological mechanism involved in the relationship between Tregs and the stem cells that make hair follicles do their job.

To do this, they took genetically modified mice whose Treg cells could be 'knocked out' with a simple intervention.

The researchers clipped the hair on the mice's backs and then applied a depilatory cream for 30 seconds - when you depilate the skin, hair follicles kick into the active hair growth phase.

They monitored the hair regrowth for 14 days, comparing the regrowth between control mice and the ones whose Tregs they had tampered with.

In mice whose Tregs were knocked out in the first three days after depilation, the hair just didn't grow back, leaving them with a bald patch on their backs.

A closer look revealed that Tregs directly trigger the activation of stem cells in the hair follicle through a well-known cell communication mechanism called the Notch signalling pathway, which involves a specific protein called Jag1.

They even found that when they replaced Tregs with microscopic beads covered in Jag1, it triggered the activity in the hair follicles just like Tregs would.

"It's as if the skin stem cells and Tregs have co-evolved, so that the Tregs not only guard the stem cells against inflammation but also take part in their regenerative work," Rosenblum said.

"Now the stem cells rely on the Tregs completely to know when it's time to start regenerating."

It's a really elegant demonstration of a previously unknown mechanism for hair growth in mice, but there's a lot more work to be done before we can tell whether defective skin Tregs could be the culprits behind hair loss in humans.

But there's at least one tantalising clue that the study is onto something here. In genome-wide association studies of alopecia areata, a condition characterised by 'patchy' hair loss, researchers have found mutations on genes that are involved in Treg function.

Next up, the researchers are hoping to expand their results and investigate how Tregs in the skin could be involved in wound healing, and also various hair loss conditions in humans.

"It will be important to determine whether this principle extends to human diseases of epithelial dysfunction and whether Tregs can be exploited to develop new therapies for stem-cell-mediated tissue regenerative disorders," they write in the study.

These new results are also an exciting addition to the growing body of knowledge scientists have about hair growth. Earlier this month, researchers reported the discovery of a protein that causes skin stem cells to develop into hair cells in mice. They are now investigating whether this protein is involved in hair loss in people.

The research has been published in Cell.

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We now have the first evidence that immune cells in the skin directly ... - ScienceAlert

What do space travel, rodents and a bone-building protein all have in common? A team of UCLA scientists is bringing these three elements together to test an experimental drug that could one day result in a treatment for osteoporosis, which affects more than 200 million people worldwide.

The drug could also potentially help those with bone damage or loss, a condition that afflicts people with traumatic bone injury, such as injured military service members, as well as astronautswho lose bone density while in space.

Led by Dr. Chia Soo and Dr. Kang Ting, who met and married while working on this project, as well as Dr. Ben Wu, the UCLA research team is scheduled to send40 rodents to the International Space Station this week. Once there, the rodents will receive injections of the experimental drug, which is based on a bone-building protein called NELL-1. The project is being done in collaboration with NASA and the Center for the Advancement of Science in Space, which manages the U.S. National Laboratory on the space station.

This is really a pivotal point in the study of NELL-1s effect on bone density, said Soo, principal investigator on the study, the vice chair for research in the UCLA Division of Plastic and Reconstructive Surgery, and a member of theUCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research. We would not be at this point without many years of funding and support from the National Institutes of Health, the California Institute for Regenerative Medicine and several UCLA departments and centers. We are honored to conduct the next phase of our research in the U.S. National Laboratory.

The UCLA researchers have been conducting studies on NELL-1 for more than 18 years and were excited when Julie Robinson, NASA's chief scientist for the International Space Station Program, visited UCLA in early 2014 and encouraged them to submit a grant that would fund their NELL-1 research in space. The teamreceived the necessary fundingfrom the Center for the Advancement of Science in Space in September 2014 to move forward with the project.

The preparations have been very exciting; weve had conference calls with NASAs Ames Research Center every two weeks to go over all the fine details, said Dr. Jin Hee Kwak, an assistant professor of orthodontics in theUCLA School of Dentistryand project manager on the study. Everything is choreographed down to the tiniestdetails, such as whetheryoure going to fill a syringe half way or all the way that small amount affects the total weight of the rocket.

SpaceXs Dragon spacecraft is currently targeted to blast off from Kennedy Space Center in Florida today. It will bethe first time that UCLA scientists send rodents to the International Space Station. After living in microgravity and receiving NELL-1 injections for about four weeks, half of the rodents will return from space andland in the Pacific Ocean off the coast of Baja, California.

This marks the first time that American researchers will bring back live rodents from the International Space Station. After retrieval, the rodents will be returned to UCLA where they will continue to receive the NELL-1 drug for an additional four weeks. The remaining half of the rodents that stay in the space station will also receive an additional four-week dosage of the drug and will return to UCLA later.

To prepare for the space project and eventual clinical use, we chemically modified NELL-1 to stay active longer, said Wu, who is chair of the division of advanced prosthodontics in the UCLA School of Dentistry and professor in the schools of engineering and medicine. We also engineered the NELL-1 protein with a special molecule that binds to bone, so the molecule directs NELL-1 to its correct target, similar to how a homing device directs a missile.

Discovered in 1996 by Ting, NELL-1 has a powerful effect on tissue-specific stem cells that create bone-building cells called osteoblasts. When exposed to NELL-1, the stem cells create osteoblasts that are much more effective at building bone. Furthermore, NELL-1 reduces the function of osteoclasts, which are the cells that break down bone.

Ourpreclinical studiesshow that NELL-1s dual effect on both osteoblasts and osteoclasts significantly increases bone density, said Ting, chair of the section of orthodontics and the division of growth and development in the UCLA School of Dentistry.

After the age of 50, humans typically lose about 0.5 percent of their bone mass each year. But in space, bone loss significantly increases due to the lack of gravity. It is commonly known that bone density is improved by physical activity that puts pressure on bone, which helps it stay strong. Without gravitys pressure, astronauts can lose around 1.5 percent of their bone mass each month. Therefore, space is an ideal testing environmentfor NELL-1s effect on bone density.

Courtesy of Techshot, Inc.

A bone densitometer will accompany the mice to the space station. It measures the bone density of the animals.

Research on NELL-1 is supported by past or current grants from the National Institute of Dental and Craniofacial Research, the National Institute of Arthritis and Musculoskeletal and SkinDiseases, the California Institute for Regenerative Medicine, the UCLA Broad Stem Cell Research Center, the UCLA School of Dentistry, the UCLA Department of Orthopaedic Surgery and the UCLA Orthopaedic Hospital Research Center.

The experimental NELL-1 drug described above is used in preclinical tests only and has not been tested in humans or approved by the Food and Drug Administration as safe and effective for use in humans.

Wu, Ting and Soo are inventors on multiple NELL-1-related patents and principalfounders of Bone Biologics Corp., which is a licensee of NELL-1 patents from the UC Regents. The UC Regents also hold equity in the company.

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Mice headed for space to test bone-building drug developed at UCLA - UCLA Newsroom

State Senator Anthony J. Portantino closed out the Senate Budget Subcommittee on Education last week with several important additions and ratifications to Gov. Jerry Browns recently released revised budget.

Among the highlights that Portantinos subcommittee added are a proposal to increase Cal Grants for community college students, to include additional funding for transportation and other costs associated with attending college; funding childcare; funding for After-School Education and Safety (ASES); increasing accountability and transparency at the University of California; and including funding for the Summer Institute for Emerging Managers and Leaders (SIEML) initiated by Portantino when he was in the State Assembly.

The SIEML institute is a summer program for undergraduate students from historically black colleges and Hispanic-serving institutes at the seven University of California Business Schools. The funding is intended to fund the school-based institute and bring accountability to the UC Office of the President to administer the program.

The subcommittee also accepted Gov. Browns proposal to create a continuous appropriation to the University of California Davis Cord Blood Collection Program. This is another successful program initiated by Portantino that is providing life-saving cord blood stem cells to Californias diverse population.

The subcommittee also included $16 million to implement an updated History-Social Science curriculum framework with guidelines for public school teachers, something that is of particular to the 25th Senate District as the study of the Armenian Genocide is one of the subject areas.

Another major step the subcommittee took is that is restored Cal Grants for nonprofit colleges. Gov. Brown had originally proposed to only partially fund Cal Grants for Latino students, then added some restrictions that would make it difficult for students at these schools. The Subcommittee approved full funding of the Cal Grants but rejected the strings attached to them.

The subcommittee also accepted the increase in the Local Control Funding Formula (LCFF); implementation of the LCFF helps many of the school districts across the 25th Senate District and the San Gabriel Valley.

After proposing that Gov. Brown not defer nearly a billion dollars in Proposition 98 funding in the January budget, the subcommittee accepted the governors May revised plan to fully fund this money to K12 districts. It also deferred action to the full Senate Budget Committee Gov. Browns plan to add an additional billion dollars to K12 but make this money available only in 2019.

It is our subcommittees job to review the Governors plan for education in California and reject, approve or improve on his proposals, Portantino said. I was very pleased with the committees work and proud of my colleagues for preparing this plan for our students and families. From here our plan goes to the full Senate Budget Committee for deliberation and completion.

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Budget Subcommittee Chair Portantino Submits Funding Plan - Pasadena Now

May 15, 2017 Near-infrared light is used to precisely engineer stem cells into tissue. Credit: University of California - Santa Barbara

Nothing beats nature. The diverse and wonderful varieties of cells and tissues that comprise the human body are evidence of that.

Each one of us starts out as a mass of identical, undifferentiated cells, and thanks to a combination of signals and forces, each cell responds by choosing a developmental pathway and multiplying into the tissues that become our hearts, brains, hair, bones or blood. A major promise of studying human embryonic stem cells is to understand these processes and apply the knowledge toward tissue engineering.

Researchers in UC Santa Barbara's departments of Chemistry and Biochemistry, and of Molecular, Cellular and Developmental Biology have gotten a step closer to unlocking the secrets of tissue morphology with a method of three-dimensional culturing of embryonic stem cells using light.

"The important development with our method is that we have good spatiotemporal control over which cellor even part of a cellis being excited to differentiate along a particular gene pathway," said lead author Xiao Huang, who conducted this study as a doctoral student at UCSB and is now a postdoctoral scholar in the Desai Lab at UC San Francisco. The research, titled "Light-Patterned RNA Interference of 3D-Cultured Human Embryonic Stem Cells," appears in volume 28, issue 48 of the journal Advanced Materials.

Similar to other work in the field of optogeneticswhich largely focuses neurological disorders and activity in living organisms, leading to insights into diseases and conditions such as Parkinson's and drug addictionthis new method relies on light to control gene expression.

The researchers used a combination of hollow gold nanoshells attached to small molecules of synthetic RNA (siRNA)a molecule that plays a large role in gene regulationand thermoreversible hydrogel as 3D scaffolding for the stem cell culture, as well as invisible, near-infrared (NIR) light. NIR light, Huang explained, is ideal when creating a three-dimensional culture in the lab.

"Near-infrared light has better tissue penetration that is useful when the sample becomes thick," he explained. In addition to enhanced penetrationup to 10 cm deepthe light can be focused tightly to specific areas. Irradiation with the light released the RNA molecules from the nanoshells in the sample and initiated gene-silencing activity, which knocked down green fluorescent protein genes in the cell cluster. The experiment also showed that the irradiated cells grew at the same rate as the untreated control sample; the treated cells showed unchanged viability after irradiation.

Of course, culturing tissues consisting of related but varying cell types is a far more complex process than knocking down a single gene.

"It's a concert of orchestrated processes," said co-author and graduate student researcher Demosthenes Morales, describing the process by which human embryonic stem cells become specific tissues and organs. "Things are being turned on and turned off." Perturbing one aspect of the system, he explained, sets off a series of actions along the cells' developmental pathways, much of which is still unknown.

"One reason we're very interested in spatiotemporal control is because these cells, when they're growing and developing, don't always communicate the same way," Morales said, explaining that the resulting processes occur at different speeds, and occasionally overlap. "So being able to control that communication on which cell differentiates into which cell type will help us to be able to control tissue formation," he added.

The fine control over cell development provided by this method also allows for the three-dimensional culture of tissues and organs from embryonic stem cells for a variety of applications. Engineered tissues can be used for therapeutic purposes, including replacements for organs and tissues that have been destroyed due to injury or disease. They can be used to give insight into the body's response to toxins and therapeutic agents.

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Researchers at the University of Washington have successfully created a line of human embryonic stem cells that have the ability to develop into a far broader range of tissues than most existing cell lines.

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Researchers develop a more precise and controlled method of ... - Phys.Org

After 20 years of trying, scientists have transformed mature cells into primordial blood cells that regenerate themselves and the components of blood. The work, described today inNature, offers hope to people with leukaemia and other blood disorders who need bone-marrow transplants but cant find a compatible donor. If the findings translate into the clinic, these patients could receive lab-grown versions of their own healthy cells.

One team, led by stem-cell biologist George Daley of Boston Childrens Hospital in Massachusetts, created human cells that act like blood stem cells, although they are not identical to those found in nature. A second team, led by stem-cell biologist Shahin Rafii of Weill Cornell Medical College in New York City, turned mature cells from mice into fully fledged blood stem cells.

For many years, people have figured outparts of this recipe, but theyve never quite gotten there, says Mick Bhatia, a stem-cell researcher at McMaster University in Hamilton, Canada, who was not involved with either study. This is the first time researchers have checked all the boxes and made blood stem cells.

Daleys team chose skin cells and other cells taken from adults as their starting material. Using a standard method, they reprogrammed the cells intoinduced pluripotent stem (iPS) cells, which are capable of producing manyother cell types. Until now, however, iPS cells have not been morphed into cells that create blood.

The next step was the novel one: Daley and his colleagues inserted seven transcription factorsgenes that control other genesinto the genomes of the iPS cells. Then they injected these modified human cells into mice to develop. Twelve weeks later, the iPS cells had transformed into progenitor cells capable of making the range of cells found in human blood, including immune cells. The progenitor cells are tantalizingly close to naturally occurring haemopoetic blood stem cells, says Daley.

Bhatia agrees. Its pretty convincing that George has figured out how to cook up human haemopoetic stem cells, he says. That is the holy grail.

By contrast, Rafiis team generated true blood stem cells from mice without the intermediate step of creating iPS cells. The researchers began by extracting cells from the lining of blood vessels in mature mice. They then inserted four transcription factors into the genomes of these cells, and kept them in Petri dishes designed to mimic the environment inside human blood vessels. There, the cells morphed into blood stem cells and multiplied.

When the researchers injected these stem cells into mice that had been treated with radiation to kill most of their blood and immune cells, the animals recovered. The stem cells regenerated the blood, including immune cells, and the mice went on to live a full lifemore than 1.5 years in the lab.

Because he bypassed the iPS-cell stage, Rafii compares his approach to a direct aeroplane flight, and Daleys procedure to a flight that takes a detour to the Moon before reaching its final destination. Using the most efficient method to generate stem cells matters, he adds, because every time a gene is added to a batch of cells, a large portion of the batch fails to incorporate it and must be thrown out. There is also a risk that some cells will mutate after they are modified in the lab, and could form tumours if they are implanted into people.

But Daley and other researchers are confident that the method he used can be made more efficient, and less likely to spur tumour growth and other abnormalities in modified cells. One possibility is to temporarily alter gene expression in iPS cells, rather than permanently insert genes that encode transcription factors, says Jeanne Loring, a stem-cell researcher at the Scripps Research Institute in La Jolla, California. She notes that iPS cells can be generated from skin and other tissue that is easy to access, whereas Rafiis method begins with cells that line blood vessels, which are more difficult to gather and to keep alive in the lab.

Time will determine which approach succeeds. But the latest advances have buoyed the spirits of researchers who have been frustrated by their inability to generate blood stem cells from iPS cells. A lot of people have become jaded, saying that these cells dont exist in nature and you cant just push them into becoming anything else, Bhatia says. I hoped the critics were wrong, and now I know they were.

This article is reproduced with permission and wasfirst publishedon May 17, 2017.

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Lab-Grown Blood Stem Cells Produced at Last - Scientific American

Are Californians getting their moneys worth for the $3 billion they invested in stem cell science in 2004? Is there cause for optimism that major breakthrough discoveries are about to happen? What is holding back stem cell treatments from reaching patients?

These are some of the issues to be addressed Thursday in San Diego at a special stem cell meeting thats free and open to the public.

The session is sponsored by Californias stem cell agency and UC San Diego, a major hub of stem cell research and experimental treatment.

The event is the first in a statewide outreach tour by the California Institute for Regenerative Medicine, or CIRM.

The agency is projected to run out of money in 2020 unless more money is raised from public or private sources, and the series of forums is partly meant as a way to persuade voters to further support the institute with more funding.

The free event Stem Cell Therapies and You is slated for noon to 1:00 p.m. at the Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, across from the Salk Institute in La Jolla.

Four speakers at Thursdays event are to discuss the state of stem cell research:

-- Catriona Jamieson, director of the UC San Diego Alpha Stem Cell Clinic and an expert on blood cancers

-- Jennifer Briggs Braswell, executive director of the Sanford Stem Cell Clinical Center, another stem cell clinic at UCSD

-- David Higgins, a patient advocate for Parkinsons on the CIRM board, and a San Diegan

-- Jonathan Thomas, chairman of CIRMs governing board

Boosted with the $3 billion in bond money raised through Proposition 71 (not including the additional $3 billion in interest that taxpayers are also repaying), California has become an international leader in stem cell exploration.

The money has helped attract top-notch scientists from across the country to work in this state, and it has underpinned much of the training for new researchers in this field.

While encouraging reports of individual patients being cured with experimental stem cell therapies have emerged in recent years, no stem cell-based treatment developed in this state has been approved for commercial use.

This lack of therapies on the market has resulted in some criticism that stewards of Californias groundbreaking effort have spent lavishly on researchers and the infrastructure that supports them instead of focusing on how to more quickly turn lab discoveries into usable products and technologies for the public.

In January, the biomedical news site Stat published a lengthy and critical analysis of CIRMs record in clinical trials, quoting critics who said Prop. 71s supporters shamelessly oversold the initiative as providing quick cures.

The airwaves were swamped with guys in white coats who were identified with their academic affiliation even though they were principals of private companies (some of which later got CIRM grants), and basically saying, Were going to have cures by Christmas. Marcy Darnovsky, who directs the Berkeley-based Center for Genetics and Society, was quoted as saying in the Stat article.

Providing answers

Supporters of CIRM and the programs it has backed financially said it can take many years to effectively translate research into treatments, especially when ensuring safety is paramount. The agency is supporting about 30 clinical trials, including some at its own alpha stem cell clinics, combining treatment with research support.

Jonathan Thomas, CIRMs chairman, said the San Diego event and others like it in other parts of the state are meant to update patients and all Californians about how their money has been spent, and to hear from the public. While San Diego will be in the spotlight at this meeting, work throughout CIRM will be discussed.

San Diego has received a lot of money from CIRM, including about $60 million that has gone to ViaCyte, developer of a stem cell-based implant that could produce a functional cure for Type 1 diabetes.

Many San Diego County stem cell researchers have received grants for various projects. These include David Schubert of the Salk Institute for Biological Studies, for stem cell-based development of an Alzheimers drug; Robert Wechsler-Reya of Sanford Burnham Prebys Medical Discovery Institute, to determine the role of neural stem cells in growth, regeneration and cancer; and Bianca Moth of Cal State San Marcos, to train students for a career in stem cell research.

The Sanford Consortium for Regenerative Medicine building, where the Thursday meeting will be held, was constructed with $43 million from CIRM toward its total price tag of $127 million.

Four clinical trials are taking place at UC San Diegos alpha stem cell clinic, said Larry Goldstein, director of the universitys stem cell program.

These are the diabetes treatment being developed with ViaCyte; a treatment for spinal cord injury derived from human fetal cells; a chronic heart failure therapy using mesenchymal stem cells; and a drug called cirmtuzumab that targets cancer stem cells for chronic lymphocytic leukemia. (Yes, the drug was named after CIRM, which supported its research and development.)

Other stem cell treatments are taking place at UC San Diego outside the alpha clinic, Goldstein said. They include one from Kite Pharma of Santa Monica, using genetically modified immune cells called CAR T cells. The trial is being handled through the universitys bone marrow transplant program at Moores Cancer Center because CAR T cell therapy amounts to a bone marrow transplant.

Safety requires time

All these trials need time because patient safety is being evaluated, Goldstein said. That process can consume years.

So far, they all look safe, which is terrific news, Goldstein said.

Other stem cell trials at the alpha clinic are incipient, he said, including for osteoarthritis using mesenchymal and stromal cells, taken from bone marrow and fat tissue. Numerous stem cell clinics offer treatment with these cells, including some operating in a legal gray zone, outside the clinical trial system.

Goldstein said UCSD plans to better study these poorly defined cells, and what they can do, before beginning treatment. Part of that includes building a genetic profile of these cells, using a method called single cell RNA seq.

Once weve got a better handle on what those cells look like, wed like to put them into clinical trials, he said.

Its especially important that we get a handle on patient-to-patient variability, Goldstein said. We expect there will be variability. Most things in humans are. But to my knowledge, the clinics that are using this methodology dont have a logical and rigorous ability to take advantage of that variability to treat human patients.

bradley.fikes@sduniontribune.com

(619) 293-1020

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Should Californians give more money for stem cell research? - The San Diego Union-Tribune