Magenta Nabs More Cash, Licenses Drug To Boost Transplant Pipeline – Xconomy

By NEVAGiles23

Xconomy Boston

Magenta Therapeutics said today it has doubled its money with a $50 million Series B round led by GV, formerly Google Ventures. The Cambridge, MA-based startup spun out of Harvard University last year with nearly $50 million in launch money to develop improved bone marrow transplants.

Magenta has also licensed a drug from Novartis that it says could help boost the number of healthy stem cells that are delivered into a patients body, a key procedure in a transplant.

Used to treat people with cancer and other blood-borne diseases, a bone marrow transplant starts with a procedure to kill a patients diseased blood stem cells, which live in the bone marrow. The diseased cells are then replaced with healthy stem cells, usually from a donor. Though growing safer, its still a risky process, especially for elderly or frail patients. Deaths related to the treatment have dropped below 20 percent in recent years, but Magentas founders as well as researchers at Stanford University are among the groups working to improve the complicated steps.

Magenta is developing three types of drugs, each for a different procedure in the transplant process. It will test them as separate products but try to market them as a suite to transplant clinics, according to management.

The drug Magenta licensed from Novartis is applied to cells from donated umbilical cord blood, which have different properties than cells from blood donated by adults. The drug, which recently completed an early stage study, is meant to stimulate the blood cells to replicate faster outside the body, providing a bigger population to put back into the patient. The more cells, the better the chance that the new healthy cells will engraft, or survive in the patients bone marrow.

Magenta also aims to develop an alternative to chemotherapy or radiation, which a patient receives before a transplant to kill his or her diseased stem cells; and a treatment to coax an adult donors stem cells out of the bone marrow and into the bloodstream, where the cells are easier to harvest for the transplant.

Other investors in the new round are previous backers Third Rock Ventures, Atlas Venture, Partners Innovation Fund, and Access Industries, and new investors including Casdin Capital and BeTheMatch BioTherapies, which is affiliated with the nonprofit international bone marrow registry NMDP/Be The Match.

Magenta said it would work with BeTheMatch BioTherapies on research and development.

Photo Bone Marrow Donation by Andrew Ratto via a Creative Commons 2.0 license.

Alex Lash is Xconomy's National Biotech Editor. He is based in San Francisco.

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May 2nd, 2017

Magenta Therapeutics Advances Stem Cell Transplantation Strategy … – Business Wire (press release)

By JoanneRUSSELL25

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Magenta Therapeutics, a biotechnology company developing therapies to improve and expand the use of curative stem cell transplantation for more patients, today announced rapid progress in advancing the companys strategic vision, including the completion of a $50 million Series B financing; in-licensing a clinical-stage program from Novartis to support the use of stem cell transplantation in a variety of disease settings; and a strategic partnership with Be The Match BioTherapiesSM, an organization offering solutions for delivering autologous and allogeneic cellular therapies.

The financing announced today is intended to fuel development of innovative product candidates across multiple aspects of transplantation medicine, including more precise preparation of patients, stem cell harvesting and stem cell expansion. The Series B round, which was oversubscribed, was led by GV (formerly Google Ventures), with participation from all existing investors, including Atlas Venture, Third Rock Ventures, Partners Innovation Fund and Access Industries. The financing also included Casdin Capital and other crossover investors, as well as Be The Match BioTherapies, a subsidiary of National Marrow Donor Program(NMDP)/Be The Match, the worlds leading organization focused on saving lives through bone marrow and umbilical cord blood transplantation.

Magenta has quickly established itself as a nexus of innovation in stem cell science, catalyzing interest in this area of medicine with the recognition that improvements will have profound impact on patients, said Jason Gardner, D. Phil., chief executive officer, president and cofounder of Magenta Therapeutics. We aspire to accelerate products that could unleash the potential of transplantation to more patients, including those with autoimmune diseases, genetic blood disorders and cancer. The resounding interest in Magenta from such a high-quality set of investors is a testament to our solid progress since launch, including building a world-class team and a robust pipeline, and generating promising early data.

MGTA-456: Investigational Product Addressing Significant Unmet Need in Stem Cell Transplant

The clinical-stage program in-licensed by Magenta from Novartis, MGTA-456 (formerly HSC835), aims to expand the number of cord blood stem cells used in transplants to achieve superior clinical outcomes compared to standard transplant procedures, and to enable more patients to benefit from a transplant. Under this agreement, Magenta gains rights to use MGTA-456 in selected applications and will develop MGTA-456 in multiple diseases, including immune and blood diseases.

Early results published in Science1 demonstrated the ability of MGTA-456 to significantly increase the number of umbilical cord blood stem cells. Clinical results reported in Cell Stem Cell2 demonstrated that this approach yielded an increased expansion of stem cells.

John E. Wagner, M.D., executive medical director of the Bone Marrow Transplantation Program at the University of Minnesota and the studys lead author, stated: MGTA-456 markedly shortens time to recovery, addressing one of the most significant challenges in stem cell transplantation today. MGTA-456 achieved a remarkable increase in the number of blood-forming stem cells, greater than that observed by all other methods that have been tested to date. This product has the potential to further improve cord blood transplant outcomes.

Be The Match BioTherapies Strategic Partnership Agreement

Magenta and Be The Match BioTherapies also announced today that in addition to the equity investment, the two organizations have initiated a collaboration to support their shared goals of improving transplant medicine. Magenta and Be The Match BioTherapies will explore opportunities to work together across all of Magentas research efforts, from discovery through clinical development. Under this agreement, Magenta may leverage Be The Match BioTherapies capabilities, including its cell therapy delivery platform, industry relationships, clinical trial design and management, and patient outcomes data derived from the NMDP/Be The Match, which operates the largest and most diverse marrow registry in the world. NMDP/Be The Match has a network of more than 486 organizations that support marrow transplant worldwide, including 178 transplant centers in the United States and more than 45 international donor centers and cooperative registries.

We are proud to have made our first equity investment as an organization in Magenta Therapeutics, and we share a vision to improve and advance the use of curative stem cell transplantation for patients with a wide range of diseases, said Amy Ronneberg, president of Be The Match Biotherapies.

About Magenta Therapeutics

Magenta Therapeutics is a biotechnology company harnessing the power of stem cell science to revolutionize stem cell transplantation for patients with immune- and blood-based diseases. By creating a platform focused on critical areas of transplant medicine, Magenta Therapeutics is pioneering an integrated, but modular approach to stem cell therapies to create patient benefits. Founded by internationally recognized leaders in stem cell transplant medicine, Magenta Therapeutics was launched in 2016 by Third Rock Ventures and Atlas Venture and is headquartered in Cambridge, Mass. For more information, please visitwww.magentatx.com.

About Third Rock Ventures

Third Rock Ventures is a leading healthcare venture firm focused on investing and launching companies that make a difference in peoples lives. The Third Rock team has a unique vision for ideating and building transformative healthcare companies. Working closely with our strategic partners and entrepreneurs, Third Rock has an extensive track record for managing the value creation path to deliver exceptional performance. For more information, please visit the firms website atwww.thirdrockventures.com.

About Atlas Venture

Atlas Venture is a leading biotech venture capital firm. With the goal of doing well by doing good, we have been building breakthrough biotech startups since 1993. We work side by side with exceptional scientists and entrepreneurs to translate high impact science into medicines for patients. Our seed-led venture creation strategy rigorously selects and focuses investment on the most compelling opportunities to build scalable businesses and realize value. For more information, please visitwww.atlasventure.com.

About GV

GV provides venture capital funding to bold new companies. In the fields of life science, healthcare, artificial intelligence, robotics, transportation, cyber security, and agriculture, GV's companies aim to improve lives and change industries. GV's team of world-class engineers, designers, physicians, scientists, marketers, and investors work together to provide these startups exceptional support on the road to success.

Launched as Google Ventures in 2009, GV is the venture capital arm of Alphabet, Inc. GV helps startups interface with Google, providing unique access to the worlds best technology and talent. GV has $2.4 billion under management and is headquartered in Mountain View, California, with offices in San Francisco, Boston, New York, and London. Launched as Google Ventures in 2009, GV is the venture capital arm of Alphabet, Inc. For more information, please visit http://www.gv.com.

About Be The Match BioTherapies

Be The Match BioTherapies partners with organizations pursuing new life-saving treatments in cellular therapy. Built on the foundation established over the last 30 years by theNMDP/Be The Match, the organization has unparalleled experience in personalized patient management with a single point of contact, cell sourcing and collection, cell therapy delivery platform, immunogenetics and bioinformatics, research and regulatory compliance. By leveraging proven capabilities and established relationships, Be The Match BioTherapies can bring customizable solutions to organizations in every stage of cellular therapy developmentfrom discovery through commercialization. Discover how Be The Match BioTherapies can assist your company atBeTheMatchBioTherapies.com.

For more information on todays announcement, see Jason Gardners post in the Life Sci VC blog: https://lifescivc.com/2017/05/building-a-bioteth-a-triple-play/.

1Science.2010 Sep 10;329(5997):1345-8. 2Cell Stem Cell.2016 Jan 7;18(1):144-55.

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May 2nd, 2017

Mouse teeth shown to hold insight into future stem cell tissue regeneration – Bel Marra Health

By daniellenierenberg

Home Health News Mouse teeth shown to hold insight into future stem cell tissue regeneration

The use of stem cells throughout the years has been both a decisive topic and one that holds a lot of promise for potential medical therapy. They are essentially undifferentiated biological cells that havent yet been specialized for a specific purpose. The cells of your heart, stomach, and even your brain have all started out as stem cells, and it wasnt until some point during human development that biological processes channeled them to permanently becoming one type of cell. Scientists and researchers around the globe are always in search of the best way to learn about and harvest these valuable cells, and the latest reports suggest the teeth of rodents are an abundant source.

There are considered two main stem cell types in the body: one is from embryonic development when in the womb, and the other are adult stem cells that exist throughout the body. Harvesting embryonic stem cells has been controversial, as it often seen as unethical, but adult stem cellsfound in organs such as the bone marrow, blood vessel, and liver in mammalsis easier to obtain. Stomach linings, for example, require the constant shedding of their cell linings as the acid wears away at them, and having adult stems cells allows for quick replacement of these sloughed off cells.

Weve all seen mice before, and one of their defining characteristics are their front teeth. What most people arent aware of is that their front teeth, or incisors, constantly grow, as they rely on them to be consistently sharp for burrowing and self-defense, and of course, for eating away at your pantry food. As we grow older our teeth start to wear out, and in nature, once you dont have your teeth anymore, you die. As a result, mice and many other animals from elephants to some primates can grow their teeth continuously. Our labs objective is to learn the rules that let mouse incisors grow continuously to help us one day grow teeth in the lab, but also to help us identify general principles that could enable us to understand the processes of tissue renewal much more broadly, said UC San Franciscos Ophir Klein, MD, Ph.D., a professor of orofacial sciences in UCSFs School of Dentistry and of pediatrics in the School of Medicine.

While not all aspects of this process are fully understood just yet, as the exact signals triggering this process have yet to be identified. It, however, marks an advancement of knowledge in the field, and one that bodes well for the future of stem cell therapy. It may prove beneficial for tissue regeneration to treat everything from severe burns to growing entire organs from scratch.

Related:Stem cells from fat may be useful to prevent aging

Benefit planned May 5-6 for area leukemia victim – SalemNews.net

By NEVAGiles23

A benefit rummage, bake and vendor sale will be held this Friday and Saturday for Trisha Suits, a Lisbon resident battling leukemia. She is shown with her mother, Alice Loy, and 6-year-old son Landon who proudly displays the jacket Trisha wore while serving as an assistant cross country coach at Lisbon. Despite being virtually blind, the David Anderson High School graduate ran cross country in high school. (Salem News photo by J.D.Creer)

WHAT: Rummage, bake and vendor sale to benefit area resident Trisha Suits who will be undergoing leukemia treatments at the Cleveland Clinic.

WHEN: From 9 a.m.-4 p.m. Friday and Saturday, May 5-6.

WHERE: Guilford Lake Ruritan Hall, state Route 172.

She was born weighing just a pound and eight ounces. But Trisha Suits is hardly a lightweight.

The courageous 30-year-old Lisbon resident, left virtually blind due to her premature birth, has taken on all comers throughout her life. Despite having only 2 percent vision in her right eye and none in her left, she has been a capable mom in helping to raise her son. She is a 2006 David Anderson High School graduate. Remarkably, she ran as a member of the cross-country team, memorizing her routes. Just putting one foot in front of the other, Trisha quipped, saying never fell. She later served as a Blue Devils assistant coach.

Now she is confronting her biggest challenge. She has been diagnosed with a complex form of leukemia and will be undergoing bone marrow and stem cell transplants at the Cleveland Clinic. Due to ongoing treatments, she will be required to remain in the hospital for six weeks. Then she will need to stay at a nearby housing complex for another 100 days.

Trisha was diagnosed in early March, after passing out from severe blood loss. She spent a month in the Cleveland Clinic getting chemotherapy. But due to genetic mutations, she needs bone marrow and stem cell transplants to combat acute myeloid leukemia a type of cancer that starts in the blood-forming cells of marrow.

According to her aunt, Melody Hobbs of Salem, her lengthy stay at the housing complex the Transplant House of Cleveland will cost about $75 per day for just the lodging. A donor has been found. Transplant treatments are expected to begin May 11.

To help offset the costs, a combination rummage, bake and vendor sale for Trisha will be held this Friday and Saturday, May 5-6, from 9 a.m. to 4 p.m. each day at the Guilford Ruritans Hall off of state Route 172.

We just need people to come, Hobbs said. We are trying to raise awareness to get more people out there. All the money raised will pay for Trishas lodging and transportation.

Trishas ordeal is and will continue to be grueling. Admittedly, she gets bitter, angry and frustrated. The uncertainty is overwhelming.

The really hard part of it will be being in Cleveland away from her son and family, said Hobbs.

Indeed, Trishas said her hobby is being the best mom she can be for her son. Six-year-old Landon is a McKinley Elementary School student.

I love my mommy, he offered. Its not just my moms fight, its our fight.

Trisha and her son lives with her parents, Rick Joy and Alice Loy. Her sister, Summer Burkholder, is a co-organizer of this weekends benefit.

The transplants offer a possible cure. Without them, it would be dire.

God only gives me what I can handle, said Trisha who has spent her entire life combating challenges. But I am scared about what this is going to do to my body.

Ongoing updates on Trisha may be found on Facebook. Visit: Trishas Fight with AML. To make an online donation, a link: youcaring.com may be accessed.

jdcreer@salemnews.net

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May 1st, 2017

How you can give yourself a chance to save another’s life – Glenwood Springs Post Independent

By daniellenierenberg

Few things could start out so simple and yet maybe lead you to save a life. But one woman's firsthand experience led precisely down that road, and now she's getting more people on board.

Be the Match is a program offering free kits for people to submit their DNA through mouth swabs to see if they might one day be a match to donate to someone with blood cancers or other blood-based diseases.

And getting that opportunity is about to become even easier for those in the Roaring Fork Valley this coming First Friday (May 5) and then on Dandelion Day (May 13) in Carbondale.

Erica Borum, who works as a civil engineer for the White River National Forest, is setting up a Be the Match booth at these events, where she'll have registry kits with mouth swabs ready to be used and sent off.

This first step is simple. If you're between 18 and 44 you can participate, but this first step doesn't mean that you're automatically going to be donating to someone.

Your mouth swab puts you on a DNA registry. Once your DNA is on the list, that information is available to doctors looking for donors who match with patients in need for stem cells or bone marrow.

According to Be the Match, each year about 14,000 patients are down to one option for a cure: a transplant from someone outside their family.

Borum is pushing this effort in Carbondale after her own experience a little more than a year ago donating to a man with Hodgkin's lymphoma. She wants to give people this opportunity by bringing the kits to them, but she's also on a mission to demystify the process.

"When people are first addressed with it, it's strange and weird and not something that would be of interest," she said. "I'd like to help make it not so foreign."

Borum first heard about this donation process through a friend, who knew of someone needing a bone marrow transplant for leukemia. The patient was down to her last option, but in the end the procedure worked out for her.

Borum got online and started doing her research on the organization Be the Match.

The chances that you'll be selected are actually quite slim. This isn't as simple as finding a person with matching blood type. Because doctors are looking for someone with highly specific blood markers and other characteristics to give the patient the best shot possible for a good transfer, only about one in 430 people end up being suitable match, she said.

There are two types of transfers: a transfer of peripheral blood stem cells or a bone marrow transplant. Ultimately, the patient's doctor choses which route to go, so donors need to be willing to do either.

Donating blood stem cells, which is what Borum did, is a bit like an extended blood draw.

"The first thing to know is my phobia is needles," said Borum. "But knowing that phobias are completely illogical, I went ahead and sent off my swabs. And there wasn't a great chance that I would be a match anyway.

"The prospect of going through a process that's a little uncomfortable for the benefit of saving someone, it's kind of overwhelming," she said. "To be honest, I didn't give it a second consideration, despite the phobia."

She joined the registry in 2013. The mouth swab process took only about 10 minutes, she said.

A little more than two years later, Borum got that call that she was a preliminary match. Did she want to proceed with the process?

Even agreeing at this point isn't the final say in whether you end up donating. First, Borum had her blood drawn and sent off to reinforce that, yes, she was a match. And after that was confirmed she had to get a physical and undergo some pathogen testing, a chest X-ray and some additional testing to make sure she was healthy.

During this process, the identity of the patient is guarded. All Borum was told was that the patient was a 56-year-old man with Hodgkin's lymphoma.

From there it was a repeated process of "test and we'll let you know, test and we'll let you know," she said.

'ONE POKE AT A TIME'

And as each of those came back good, they check to see if you want to proceed. The donor can pull out at any time. But while the donor is going through this process, the patient is going through a parallel preparation of intensive chemotherapy trying to kill as much of the cancer as possible before the transplant.

This is a critical stage for the patient, and if the donor opts out now, it could be life-threatening for the patient, she said.

"I took it one needle poke at a time."

Leading up to the final blood draw, Borum was given several injections of a drug to boost her cell count to help doctors withdraw the stem cells they were looking for.

On the long end, physicians say the blood draw process could take up to six hours. That was their prediction for Borum, who is more petite. During that draw, they run the first samples to a lab to confirm they're getting the right concentration. Borum's body reacted well to the blood cell-boosting drug, and the final process ended up only taking four hours.

To explain her motivation to go through with this procedure, Borum said it's part of her spiritual practice.

"I did it as part of the practice, and recognizing that a lot of things we do are self-referential and self-serving. And I don't think there's a ton of benefit in that, for myself and for others.

"I think the quote from the Dalai Lama goes: If you want others to be happy, have compassion; if you want to be happy, have compassion.

"And it's all a matter of statistics. If there are more people in the registry, it's more likely someone will have a match. If I can benefit one person, it's little effort on my end to try to boost the numbers."

Because of the statistically low chances of finding a match, getting more people on the registry is essential. And the first month or two after the final transplant is a time critical to find out whether their new blood stem cells are working. This doesn't always have a happy ending, said Borum.

But in her case, it did.

BUILDING A BOND

Her transfer was a little more than a year ago. About two months afterward she got word that her cells were successfully making the patient's blood and he had no sign of cancer cells. The patient, who Borum learned lives in New York, sent her a thank you card a few months later, and recently they've exchanged emails.

And in those exchanges, she got her first glimpses into his life.

"I am a husband of 28 years and the father of two boys and was facing a difficult future," he wrote in April of last year. "I am overwhelmed beyond words with this gift you have given me. Please know that I will live the rest of my life with the warmth of your generosity and will do my best to extend it to others in need."

"His email said that he's now been healthy for one year and two months," said Borum. He's also offered to come to Colorado to meet Borum and thank her in person.

His sickness had taken him to a point where walking was a very difficult task, but now he's running again.

The whole process, they say, is about 20 to 30 hours of your time, usually spread over about four to six weeks, according to Be the Match.

"I think that's a small sacrifice to potentially save someone," said Borum.

The patient in this case wasn't available for this article but for pretty much the best reason ever.

Borum said that after being too sick for so long, he was finally leaving for a long-awaited vacation.

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April 30th, 2017

Bone Marrow vs. Fat Derived Stem Cells Continued : Stem …

By LizaAVILA

Whether your adult mesenchymal stem cells come from bone marrow or from fat probably does not make a difference in terms of clinical results. Although some centers claim that bone marrow derived cells are superior to fat derived cells, there is no evidence to substantiate that. Recent studies show that fat derived cells make bone tissue much better than the bone marrow derived cells. Some studies are showing different outcomes but it is important to realize that these studies are all done in petri dishes and may not relate to living organism. Also, it is important that one is not mislead in some marketing materials by the word bone in bone marrow, possibly implying that since this is an orthopedic source it must be better for treating orthopedic conditions such as cartilage regeneration. In fact, the bone marrow is part of the reticulo-endothelial system (makes blood cells) and just happens to be found in the center of bone. The truth is, both bone marrow derived and stromal (from fat) derived stem cells are both effective for regenerative therapy and both have the potential to differentiate into mature functional cartilage. However, stem cells from fat are 100 to 1000 times more plentiful and this makes same day procedures (allowed in the US) much more effective with fat derived cells. The higher numbers of cells in fat leads to better clinical outcomes. Also, the quality of bone marrow declines with age and it has less numbers of cells and less healthy cells compared to the fat. The diminution in quantity and quality of bone marrow cells related to age and chronic illness is well documented. Last but not least, the ease of removing fat from under the skin using a mini-liposuction under local anesthetic is much less invasive and MUCH LESS painful than undergoing bone marrow aspiration to obtain bone marrow cells.

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Comprehensive-characterization-of-four-different-populations-of-human-mesenchymal-stem-cells-as-regards-their-immune-properties-proliferation-and-differentiation

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April 29th, 2017

The irrefutable success of stem cell treatments – Miami’s Community Newspapers

By raymumme

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In my opinion, one of the hardest things to accept is a new type of medical treatment, particularly when it changes the philosophy, parameters and overall results that we are expecting and basically used to receiving. Stem cells are undoubtedly no exception to this rule.

About six weeks ago, Eduardo K (a Cuban doctor with a Masters Degree from the University of Pittsburg in internal medicine and nephrology), brought his wife Maria to our institute, in order to assess the possibility of using stem cells to cure the severe chronic pain in her ankle; a pain so severe that it was basically hindering her ability to walk. Dr. K also expressed his extreme hesitation and concerns about having his wife involved in an invasive ankle surgery at this stage of her adult life.

However, while conducting our usual examining process, reviewing her medical records and MRIs and thoroughly discussing my overall recommendations about a potential stem cell transplant, I quickly realized that Dr. K was not a true believer in Stem Cell therapies, since he thought that there was not much medical evidence of their actual effectiveness and he ultimately also confessed that his wife had basically dragged him to accompany her to this particular appointment.

As always, I respectfully explained the reality that stem cells actually repair the damaged cartilage in a microscopic type fashion and thus, while this repair process would not be clearly reflected immediately on future X-rays, I assured them that the pain she was suffering from will soon subside and possibly even completely disappear. In addition, I expressed that I was extremely confident that she would also regain her mobility skills after the procedure, even if this improvement could not be easily detected via a radiological image.

Since Marias options were somewhat limited, added to the fact that months of traditional physical therapy, injections, medications and previous surgeries had completely failed her, Dr. K finally agreed to grant his wifes wishes to have her stem cell transplant (from her own bone marrow and fat) performed, although he was still very skeptical about the process and was showing little enthusiasm.

This morning, both of them attended our follow up appointment (six weeks after the procedure) and surprisingly, Maria and Dr. K happily confirmed that she felt at least 60 percent better, something that no previous traditional medical treatments had been able to accomplish. It was then that I explained to them that her stem cells had acted much faster than expected (something that possibly taught Dr. K an interesting lesson).

As we began to say our goodbyes, the doctor told me (first in English, then in Spanish) that: in spite of my skepticism about stem cell therapies, I can personally attest that the successful results seen on my wife have been irrefutable, and with a smile on both of their faces, they gratefully thanked my staff and I for this amazing improvement.

As I continued to replay the words expressed by this doctor over and over in my mind, I quickly realized how truly incredulous human beings tend to be, with most of us often needing to fail several times at accomplishing something before being able to realize and accept that we were truly mistaken in the first place!

So if you, a friend or relative would like to receive Stem Cell or PRP treatments, please call us at 305-598-7777. For information visit: http://www.stemcellmia.com (available in both English and Spanish), or watch our amazing video-testimonies on our YouTube Chanel and also please follow us on Facebook and Twitter. If you would like to ask a question directly to Dr. Castellanos, please do so via his direct email: stemdoc305@gmail.com.

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April 28th, 2017

Transparent Bones Enable Researchers to Observe Stem Cells Inside – Laboratory Equipment

By raymumme

Ten years ago, the bones currently in your body did not actually exist. Like skin, bone is constantly renewing itself, shedding old tissue and growing it anew from stem cells in the bone marrow. Now, a new technique developed at Caltech can render intact bones transparent, allowing researchers to observe these stem cells within their environment. The method is a breakthrough for testing new drugs to combat diseases like osteoporosis.

The research was done in the laboratory of Viviana Gradinaru (BS '05), assistant professor of biology and biological engineering and a Heritage Medical Research Institute Investigator. It appears in a paper in the April 26 issue of Science Translational Medicine.

In healthy bone, a delicate balance exists between the cells that build bone mass and the cells that break down old bone in a continual remodeling cycle. This process is partially controlled by stem cells in bone marrow, called osteoprogenitors, that develop into osteoblasts or osteocytes, which regulate and maintain the skeleton. To better understand diseases like osteoporosis, which occurs when loss of bone mass leads to a high risk of fractures, it is crucial to study the behavior of stem cells in bone marrow. However, this population is rare and not distributed uniformly throughout the bone.

"Because of the sparsity of the stem cell population in the bone, it is challenging to extrapolate their numbers and positions from just a few slices of bone," says Alon Greenbaum, postdoctoral scholar in biology and biological engineering and co-first author on the paper. "Additionally, slicing into bone causes deterioration and loses the complex and three-dimensional environment of the stem cell inside the bone. So there is a need to see inside intact tissue."

To do this, the team built upon a technique called CLARITY, originally developed for clearing brain tissue during Gradinaru's postgraduate work at Stanford University. CLARITY renders soft tissues, such as brain, transparent by removing opaque molecules called lipids from cells while also providing structural support by an infusion of a clear hydrogel mesh. Gradinaru's group at Caltech later expanded the method to make all of the soft tissue in a mouse's body transparent. The team next set out to develop a way to clear hard tissues, like the bone that makes up our skeleton.

In the work described in the new paper, the team began with bones taken from postmortem transgenic mice. These mice were genetically engineered to have their stem cells fluoresce red so that they could be easily imaged. The team examined the femur and tibia, as well as the bones of the vertebral column; each of the samples was about a few centimeters long. First, the researchers removed calcium from the bones: calcium contributes to opacity, and bone tissue has a much higher amount of calcium than soft tissues. Next, because lipids also provide tissues with structure, the team infused the bone with a hydrogel that locked cellular components like proteins and nucleic acids into place and preserved the architecture of the samples. Finally, a gentle detergent was flowed throughout the bone to wash away the lipids, leaving the bone transparent to the eye. For imaging the cleared bones, the team built a custom light- sheet microscope for fast and high-resolution visualization that would not damage the fluorescent signal. The cleared bones revealed a constellation of red fluorescing stem cells inside.

The group collaborated with researchers at the biotechnology company Amgen to use the method, named Bone CLARITY, to test a new drug developed for treating osteoporosis, which affects millions of Americans per year.

"Our collaborators at Amgen sent us a new therapeutic that increases bone mass," says Ken Chan, graduate student and co-first author of the paper. "However, the effect of these therapeutics on the stem cell population was unclear. We reasoned that they might be increasing the proliferation of stem cells." To test this, the researchers gave one group of mice the treatment and, using Bone CLARITY, compared their vertebral columns with bones from a control group of animals that did not get the drug. "We saw that indeed there was an increase in stem cells with this drug," he says. "Monitoring stem cell responses to these kinds of drugs is crucial because early increases in proliferation are expected while new bone is being built, but long-term proliferation can lead to cancer."

The technique has promising applications for understanding how bones interact with the rest of the body.

"Biologists are beginning to discover that bones are not just structural supports," says Gradinaru, who also serves as the director of the Center for Molecular and Cellular Neuroscience at the Tianqiao and Chrissy Chen Institute for Neuroscience at Caltech. "For example, hormones from bone send the brain signals to regulate appetite, and studying the interface between the skull and the brain is a vital part of neuroscience. It is our hope that Bone CLARITY will help break new ground in understanding the inner workings of these important organs."

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April 28th, 2017

Family seeks ‘miracle’ for siblings, saves lives in the process – Monroe News Star

By daniellenierenberg

Caroline, 11, Elizabeth, 3, Jon Thomas, 13 and James Christopher Allums, 20, do everything as a family. James Christopher and Elizabeth both have a rare medical condition. Their mother, Ellen Allums, said they all go through the process together and support each other with faith and love.(Photo: Courtesy)

Learning that your child has a rare, life-threatening illness is difficult for any family. Everything changes. One family learned that two of their children share the same rare blood disorder.

"That news that we heard was the worst news that we could hear, but it was the best thing that's ever happened to us. It really changed our perspective. It changed our priorities," Chris Allums said.

"We're no longer the same people we were," Ellen Allums said.

Ellen and Chrishave four childrenJames Christopher, 20,Jon Thomas, 13,Caroline,11, andElizabeth, 3.

James Christopher and Elizabeth have Fanconi anemia, a disease that affects the bone marrow's ability to produce blood. Bone marrow or blood stem cell transplants are considered the best treatments, andthey have not yet found a match for either child.

James Christopher was diagnosed 12 years ago and told he had about 18 monthsto live. The family was told he must received a bone marrow transplant.

"We immediately decided that, first of all, we're going to pray and expect a miracle and grow our faith, and next, we're going to try and see if we can find him a bone marrow match and help others along the way, see how many lives that we can affect, that we can save both spiritually and physically," Ellen said.

More than 16,000 people have been added to the worldwide bone marrow registry as a result of drives held on behalf of the Allums. Ellen said they know of at least 41 lives that have been saved because of those efforts, and they're asking more people to commit to donate.

'Looking for a double miracle'

Ellen said a doctor said someone with FA can be like a duck gliding on the water the surface appearance is calm, but people can't see all the effort that goes into staying in motion.

It has a variety of symptoms such as fatigueand can lead to bone marrow or organ failure. Ellen and Chris said FA patients are 500 times more likely to develop some cancers, such as leukemia. James Christopher is subject to constant screenings.

The disease is genetic. According to the National Organization for Rare Disorders, the incidence rate is 1 in 136,000 births. Ellen said her children are two ofsix in Louisiana affected by FA.

Elizabeth's blood counts have been OK, but doctors have said James Christopher has an immediate need for a transplant. DNA needs to be close to an exact match, and many families find a relative who can donate.Elizabeth is a 100 percent match, but she's ineligible because of her FA.

One donor, once found, could help both.A bone marrow transplant won't cure someone with FA, but it can help prolong life.

"Just because you're having to wait doesn't mean the miracle's not going to come. We've been waiting 12 years, but we still have faith that that miracle's coming. Just because it hasn't happened doesn't mean it's not going to. The timing needs to be right," Ellen said. "In our lives, we're looking for an even greater miracle because we're looking for a double miracle, with two children."

FA patients can require blood and platelet transfusions, after which they may become dependent and need additional rounds, which would require a bone marrow transplant quickly.

James Christopher received his first blood transfusion three weeks ago.

"Chris gave. His daddy gave blood to him, and we felt like it was his heavenly father and his earthly father that gave him that blood, and now we're praying and believing that he never has to receive it again," Ellen said.

She said they've dealt with some scary bleeding issues "like Niagara Falls," and James Christopher has almost lost his life a few times. His parents call him a survivor, a warrior. He gets up and stays active daily, even with low blood counts that doctors thinkwould cause fatigue.

"I love to prove doctors wrong. If they give me a boundary, I want to cross it, definitely, when it comes to that," he said. He likes to tell people "keep calm and carry on," like the World War II posters.

Every bump, scratch, scrape and bruise for the siblings is noteworthy, and the whole family works to avoid germs. A simple cough or cold could be devastating, so they're all in tune to notice illness.They're very aware of the importance of handwashing and staying home if ill. Chris said during cold and flu season, they often come in, shower and change clothes before interacting with the others.

Ellen said they respect people who choose not to vaccinate, but all of her children have been vaccinated because measles or chicken pox can kill someone with FA.

All the children home school to help prevent illness. When James Christopher was diagnosed, doctors said it could help him live longer. Chris said all four have excelled fromthe one-on-one time, and they've enjoyed getting to know other families inthe Christian Homeschool Association.

The Allums know their lives are different than those of many other families, but they are running their own race.

"I have to tell you that we have a wonderful life. Sure it's full of hard work, but it's wonderful because of what the Lord has done with it," Chris said.

Read more:Mom says prayer pulled her through transplant|Facing the storm: Mother shares unbelievable story|Big brother to the rescue: Man gives sister half of liver|Man saves 10 in life, death

Joy in the journey

The couple did their homework on hospitals that specialize in the disease and settled on Memorial Sloan Kettering Hospital's cancer center in New York. It had the best survival rates, and they've been going for 12 years.

James Christopher's and Elizabeth's immunity is low, the family cannot travel with the general public. They either have to make the almost 20-hour drive or arrange for a private plane. Ellen said they've had to go there, at times, every three to six months.

The whole family travels to medical appointments.

"Although they don't have the disease, they go through it with them," Ellen said of Jon Thomas and Caroline. She said all of her children have gone to hospitals and played with and prayed for children were facing terminal diagnoses. It's been a blessing to them and a ministry to others.

James Christopher said they try to find fun in the journey. Ellen said they do something fun every time they go to the hospital and embrace John 10:10Jesus came that we might have life and have it abundantly.

James Christopher Allums, 20, holds his sister Elizabeth Allums, 3. The siblings both have a rare medical condition called Fanconi anemia.(Photo: Courtesy)

What happens if there's a match?

"We would be moving to New York for six to eight months for the bone marrow transplant," Ellen said.

Ellen said the a bone marrow recipient with FA will have to go through chemotheraphy for two weeks to kill off the patient's natural bone marrow.

"When the cells are dead, then they receive someone else's bone marrow. It's a liquid, it looks just like an IV, and they lie there and you just pray to God that it's going to take," she said.

After the transplant, the patient is in isolation for 30-40 days. They stay at the transplant hospital for six to eight months and keep a medical mask on for one year. Chris said you hope graph vs. host disease isn't an issue.

Saving lives

She said she used to look at missions that dig wells in other countries and wish they could go save lives, but, after prayer, she realized they are saving people. With the help of family and friends, efforts to add bone marrow donors have helped dozens of people.

"I like to tell people 'You could be the reason someone lives.' ... And I think those words are pretty powerful" Ellen said.

She said the process to donate blood stem cells, which is the most common donation method, involves a needle in each arm for four to six hours.

"It's not even a surgery. It's not like giving a kidney or a lung or a heart, even, but the benefits are that strong. It can truly save a life, but yet all you have to do is like giving blood," Ellen said.

To test for a match, she said, it's even less of a commitment. It takes about five minutes to fill out paperwork and provide a swap from inside the cheek. Anyone 18-55 in good health can register.

The community has come together to help organize a drive for May 1, National Fanconi Anemia Day. A massive drive will take place at more than a dozen locations across northeastern Louisiana, and CenturyLink will be registering employees on-site.Anyone anywhere can order testing kitsonline atdkms.orgorbethematch.org.

A month after testing, people will get a phone call to confirm their position on the registry. Ellen said they pray people will make the commitment.Previous drives for the Allumshave set national records for most registered in one day. Over three days, they tested 5,000 people.

"When people come, we want to educate them on the processin hopes thatwhetherthey are a match in a month or a match in 20 yearsthat they will be committed to beingon that registry to help somebody," Chris said.

They heard of a woman who registered with her family at a previous event andlater developed leukemia. Her sister was found as an instant bone marrow match because theyalreadyhad been tested.

Ellen and Chris said knowing that 41 lives were saved as a result of their family'sefforts makes it all worth it, even though it hasn't been easy.

"But we believe that God is going to heal them both because He told us He would, and we believe that. We hold on to those promises of God. ... and we focus on that. That gives us strength," Ellen said.

Follow Bonnie Bolden on Twitter@Bonnie_Bolden_and on Facebook athttp://on.fb.me/1RtsEEP.

Want to register?

May 1 is National Fanconi Anemia Day, and a more than a dozen locations across northeastern Louisiana will be part of a single registration drive. Times vary and new locations may be added. Check The Friends of James Christopher and Elizabeth Allumson Facebook or visitcaringbridge.organd searchJames Christopher Allums.

Or order a testing kit online at dkms.org or bethematch.org.

Testing sites and times are:

Monroe

West Monroe

Surrounding parishes

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April 28th, 2017

Scientists turn bones transparent to let them see into marrow – Stat – STAT

By raymumme

ow you see it, now you dont: Scientists have used a chemical technique to make mouse bones turn transparent. The technique has been used in the past to make brains and kidneyssee-through, but this marks the first time its been used in hard tissues.

The ability to see within a bone couldhave implications for research into bone diseases, by letting researchers get a more accurate picture of bones internal structure.

The technique is called CLARITY, and since 2013, when it was first described, it has been deployed on a wide variety of mammalian tissues and inplants. Caltech neuroscientistViviana Gradinaru, an original developer of the technique, even cleared an entire mouses body in 2014 (except for its bones, which were unaffected, she said).

The approach works by chemically locking proteins and DNA in place with a hydrogel, after which researchers wash away fats within the tissue. Lipids refract light, so this washing step makes CLARITY-treated tissues transparent.

Flexible 3-D printed scaffolds could mend broken bones

In this case, Gradinaruwanted to look at bone marrow and count the number of stem cells that could ultimately produce new bone cells.

Bone is not a static organ. It iscontinuously changed. The bones we have in our body, we didnt have them 10 years ago, she explained. Acontinuous process of bone cell death and bone cell growth ishappening, spurred by progenitor cells in a bones soft, spongy marrow.

But looking for these cells can bechallenging. There arent that many progenitor cells, soextrapolating the number and distribution based ona small sample isnt ideal. Researchers can slice the bone, but cuttingcan damage the edges. Putting images of the sliced bones back together into a coherent, 3-D picture is very difficult, too.A clear bone avoidsslicing altogether.

Doug Richardson, director of imaging at the Harvard Center for Biological Imaging, said the paper represented a step forward in bone clearing. (Richardson was not involved in this research.)

This technique has the potential to monitor bone health or disease progression over larger volumes with greater accuracy, he said.

Gradinarus team has already demonstrated one possible application. They found that a drug for osteoporosis, currently being developed by Amgen, triggered an increase in the number of stem cells in CLARITY-treated bone.Some Amgen scientists were coauthors of the paper.

Using CLARITY let the team more effectively measure the rate of this increase.This is very important, because you want a controlled increase too much of an increase can lead to tumors, Gradinarusaid.

Other uses could be on the horizon. Being able to make a mouse or rat skull see-through could be useful for Gradinarus fellow neuroscientists who use implants in their research and want to establish the exact position of the impact after experiments are done.

Theres still more work to be done. For instance, finding a way to tagthe samples with antibodies without having to cut a bone in half, as researchers did in this paper would be ideal.Gradinaru also wouldnt mind some speed improvements:In this case, the CLARITY process took nearly a month.

Its not a fast method, by any means, Gradinaru said. However, the result theres no substitute for getting 3-D access to the intact bone marrow.

Kate Sheridan can be reached at kate.sheridan@statnews.com Follow Kate on Twitter @sheridan_kate

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April 28th, 2017

Bone marrow donor forgot he’d registered – Jewish Chronicle

By daniellenierenberg

Jewish Chronicle

Bone marrow donor forgot he'd registered
Jewish Chronicle
My phone rang and when I answered they said someone needed my stem cells. They asked me would I still like to donate? I went in the next day for tests and when I was deemed fit and healthy they got me to come back in for the procedure. On Tuesday the ...

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April 28th, 2017

Transparent bones enable researchers to observe the stem cells inside – Medical Xpress

By Sykes24Tracey

April 26, 2017 A mouse tibia that has been rendered transparent with Bone CLARITY. Stem cells appear distributed throughout the bone in red. The ability to see bone stem cell behavior is crucial for testing new osteoporosis treatments. Credit: Science Translational Medicine, Greenbaum, Chan, et al; Gradinaru laboratory/Caltech

The technique has promising applications for understanding how bones interact with the rest of the body.

The paper is titled "Bone CLARITY: Clearing, imaging, and computational analysis of osteoprogenitors within intact bone marrow."

Explore further: Growing new bone for more effective injury repair

More information: Alon Greenbaum et al, Bone CLARITY: Clearing, imaging, and computational analysis of osteoprogenitors within intact bone marrow, Science Translational Medicine (2017). DOI: 10.1126/scitranslmed.aah6518

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April 27th, 2017

Groundbreaking stem cell study kicks off in Northwest Florida – WEAR

By NEVAGiles23

A local stem cell study is changing the future of orthopedics.

A new study taking place at the Andrews Institute in Northwest Florida could shape the future of orthopedic surgery.

The goal of the study, spearheaded by Dr. Adam Anz and already eight years in the making, is to use stem cells to regrow cartilage.

If approved, it will be the first orthopedics study of its kind done in the United States and only the second in the entire world.

Stem cells are currently utilized most in cancer research and treatments, but Dr. Anz of the Andrews Institute wants to change that by putting regenerative medicine to the test, using stem cells to regrow knee cartilage.

The Andrews Institute already uses stem cells in certain therapies, but this new method could be a game changer.

"The bone marrow aspirate, which we're studying for knee arthritis and we can offer to patients, is the 1990's technology of stem cells," Dr. Anz said. "What we're studying is the modern way to harvest many more stem cells. That's the reason the FDA has said you need to bring this through our process before you just offer it to people."

Through a process called apheresis, stem cells are harvested from the patient with help from a synthetic hormone that promotes the body to generate more stem cells.

"Through this process we can collect millions of cells," Dr. Anz said. "Just 140 milliliters -- about a half of a coke can -- will have 140 million stem cells."

The stem cells will then be sorted, divided and injected into the patient's knee. Excess cells are stored in a nitrogen freezer at negative 181 degrees Celsius until the next round of injections, a process to be repeated over the next two years.

"If this study is successful, this will be the first approved in orthopedics in the United States," said Dr. Anz.

The study begins in May. Dr. Anz believes it will take about another five to seven years before the FDA can approve it for use in patients.

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April 27th, 2017

Surprising new role for lungs: Making blood – University of California

By LizaAVILA

Using video microscopy in the living mouse lung, UC San Francisco scientists have revealed that the lungs play a previously unrecognized role in blood production. As reported online March 22, 2017, inNature, the researchers found that the lungs produced more than half of the platelets blood components required for the clotting that stanches bleeding in the mouse circulation.

In another surprise finding, the scientists also identified a previously unknown pool of blood stem cells capable of restoring blood production when the stem cells of the bone marrow, previously thought to be the principal site of blood production, are depleted.

This finding definitely suggests a more sophisticated view of the lungs that theyre not just for respiration but also a key partner in formation of crucial aspects of the blood, said pulmonologistMark R. Looney, a professor of medicine and of laboratory medicine at UCSF and the new papers senior author. What weve observed here in mice strongly suggests the lung may play a key role in blood formation in humans as well.

The findings could have majorimplications for understanding human diseases in which patients suffer from low platelet counts, or thrombocytopenia, which afflicts millions of people and increases the risk of dangerous uncontrolled bleeding. The findings also raise questions about how blood stem cells residing in the lungs may affect the recipients of lung transplants.

The new study was made possible by a refinement of a technique known as two-photon intravital imaging recently developed by Looney and co-authorMatthew F. Krummel, a UCSF professor of pathology. This imaging approach allowed the researchers to perform the extremely delicate task of visualizing the behavior of individual cells within the tiny blood vessels of a living mouse lung.

Looney and his team were using this technique to examine interactions between the immune system and circulating platelets in the lungs, using a mouse strain engineered so that platelets emit bright green fluorescence, when they noticed a surprisingly large population of platelet-producing cells called megakaryocytes in the lung vasculature. Though megakaryocytes had been observed in the lung before, they were generally thought to live and produce platelets primarily in the bone marrow.

When we discovered this massive population of megakaryocytes that appeared to be living in the lung, we realized we had to follow this up, saidEmma Lefranais, a postdoctoral researcher in Looneys lab and co-first author on the new paper.

More detailed imaging sessions soon revealed megakaryocytes in the act of producing more than 10 million platelets per hour within the lung vasculature, suggesting that more than half of a mouses total platelet production occurs in the lung, not the bone marrow, as researchers had long presumed. Video microscopy experiments also revealed a wide variety of previously overlooked megakaryocyte progenitor cells and blood stem cells sitting quietly outside the lung vasculature estimated at 1 million per mouse lung.

The discovery of megakaryocytes and blood stem cells in the lung raised questions about how these cells move back and forth between the lung and bone marrow. To address these questions, the researchers conducted a clever set of lung transplant studies:

First, the team transplanted lungs from normal donor mice into recipient mice with fluorescent megakaryocytes, and found that fluorescent megakaryocytes from the recipient mice soon began turning up in the lung vasculature. This suggested that the platelet-producing megakaryocytes in the lung originate in the bone marrow.

Its fascinating that megakaryocytes travel all the way from the bone marrow to the lungs to produce platelets, said Guadalupe Ortiz-Muoz, a postdoctoral researcher in the Looney lab and the papers other co-first author. Its possible that the lung is an ideal bioreactor for platelet production because of the mechanical force of the blood, or perhaps because of some molecular signaling we dont yet know about.

"Its possible that the lung is an ideal bioreactor for platelet production because of the mechanical force of the blood, or perhaps because of some molecular signaling we dont yet know about."

Guadalupe Ortiz-Muoz, postdoctoral researcher in the Mark Looney Lab

In another experiment, the researchers transplanted lungs with fluorescent megakaryocyte progenitor cells into mutant mice with low platelet counts. The transplants produced a large burst of fluorescent platelets that quickly restored normal levels, an effect that persisted over several months of observation much longer than the lifespan of individual megakaryocytes or platelets. To the researchers, this indicated that resident megakaryocyte progenitor cells in the transplanted lungs had become activated by the recipient mouses low platelet counts and had produced healthy new megakaryocyte cells to restore proper platelet production.

Finally, the researchers transplanted healthy lungs in which all cells were fluorescently tagged into mutant mice whose bone marrow lacked normal blood stem cells. Analysis of the bone marrow of recipient mice showed that fluorescent cells originating from the transplanted lungs soon traveled to the damaged bone marrow and contributed to the production not just of platelets, but of a wide variety of blood cells, including immune cells such as neutrophils, B cells and T cells. These experiments suggest that the lungs play host to a wide variety of blood progenitor cells and stem cells capable of restocking damaged bone marrow and restoring production of many components of the blood.

To our knowledge this is the first description of blood progenitors resident in the lung, and it raises a lot of questions with clinical relevance for the millions of people who suffer from thrombocytopenia, said Looney, who is also an attending physician on UCSFs pulmonary consult service and intensive care units.

In particular, the study suggests that researchers who have proposed treating platelet diseases with platelets produced from engineered megakaryocytes should look to the lungs as a resource for platelet production, Looney said. The study also presents new avenues of research for stem cell biologists to explore how the bone marrow and lung collaborate to produce a healthy blood system through the mutual exchange of stem cells.

These observations alter existing paradigms regarding blood cell formation, lung biology and disease, and transplantation, said pulmonologist Guy A. Zimmerman, who is associate chair of the Department of Internal Medicine at the University of Utah School of Medicine and was an independent reviewer of the new study forNature. The findings have direct clinical relevance and provide a rich group of questions for future studies of platelet genesis and megakaryocyte function in lung inflammation and other inflammatory conditions, bleeding and thrombotic disorders, and transplantation.

The observation that blood stem cells and progenitors seem to travel back and forth freely between the lung and bone marrow lends support to a growing sense among researchers that stem cells may be much more active than previously appreciated, Looney said. Were seeing more and more that the stem cells that produce the blood dont just live in one place but travel around through the blood stream. Perhaps studying abroad in different organs is a normal part of stem cell education.

The study was supported the UCSF Nina Ireland Program in Lung Health, the UCSF Program for Breakthrough Biomedical Research, and the National Heart, Lung, and Blood Institute (NHLBI), a division of the National Institutes of Health (HL092471, HL107386 and HL130324).

It has been known for decades that the lung can be a site of platelet production, but this study amplifies this idea by demonstrating that the murine lung is a major participant in the process, said Traci Mondoro,project officer at the Translational Blood Science and Resources Branch of the NHLBI. Dr. Looney and his team have disrupted some traditional ideas about the pulmonary role in platelet-related hematopoiesis, paving the way for further scientific exploration of this integrated biology.

Additional authors included Axelle Caudrillier,Beat Mallavia,Fengchun Liu, Emily E. Thornton,Mark B. Headley,Tovo David, Shaun R. Coughlin, Andrew D. Leavitt, David M. Sayah, of UCLA; and Emmanuelle Passegu,a former UCSF faculty member who is now director of the Columbia Stem Cell Initiative at Columbia University Medical Center.

Cover photo:iStock/choja

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April 27th, 2017

Two weeks after his transplant, Jonathan Pitre battles kidney complications – Ottawa Citizen

By daniellenierenberg

Ottawa Citizen

Two weeks after his transplant, Jonathan Pitre battles kidney complications
Ottawa Citizen
Pitre, 16, was infused two weeks ago with stem-cell rich blood and bone marrow drawn from his mother's hip. The procedure, conducted as part of an ongoing clinical trial at the University of Minnesota Masonic Children's Hospital, is the only treatment ...

and more »

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Two weeks after his transplant, Jonathan Pitre battles kidney complications - Ottawa Citizen

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April 27th, 2017

Bare bones: Making bones transparent – Science Daily

By JoanneRUSSELL25

Science Daily

Bare bones: Making bones transparent
Science Daily
Ten years ago, the bones currently in your body did not actually exist. Like skin, bone is constantly renewing itself, shedding old tissue and growing it anew from stem cells in the bone marrow. Now, a new technique developed at Caltech can render ...
Scientists turn bones transparent to let them see into marrowSTAT
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April 26th, 2017

Are baby, wisdom teeth the next wave in stem cell treatment? – CNN

By Dr. Matthew Watson

It's based on experimental research that suggests stem cells extracted from the pulp of these teeth might someday regrow a lost adult tooth or offer other regenerative medicine benefits -- some potentially life-saving.

"So I'll try not to get emotional here, but my husband was diagnosed with acute myeloid leukemia in 2011," said Bassetto, of Naperville, Illinois, head of a sales team at a software company.

In 2012, her husband, James, had a stem cell transplant to restore his bone marrow and renew his blood.

"He was very fortunate. He was one of six kids, and his brother was a perfect match," she said. She noted that her two children, Madeline, 23, and Alex, 19, may not be so lucky if they develop health problems, since they have only each other; the chance of two siblings being a perfect stem cell match is only 25%.

Unfortunately, her husband's stem cell transplant was not successful. He developed graft-versus-host disease, where his brother's donated stem cells attacked his own cells, and he died shortly afterward.

However, she says, the transplant had given him a chance at a longer life.

Last year, when her son saw a dentist for wisdom tooth pain, a brochure for dental stem cell storage caught Bassetto's eye and struck a chord.

"I know stem cells have tremendous health benefits in fighting disease, and there's a lot ways they're used today," she said. "Had my husband had his own cells, potentially, his treatment could have been more successful."

Medical breakthroughs happen all the time, said Bassetto. "Who knows what potential there is 20 years, 40 years down the road, when my son is an adult or an aging adult?

"Almost like a life insurance policy, is how I viewed it," she said.

Some scientists see storing teeth as a worthwhile investment, but others say it's a dead end.

"Research is still mostly in the experimental (preclinical) phase," said Ben Scheven, senior lecturer in oral cell biology in the school of dentistry at the University of Birmingham. Still, he said, "dental stem cells may provide an advantageous cell therapy for repair and regeneration of tissues," someday becoming the basis for reconstructing bone tissue, retinas and even optic neurons.

Dr. Pamela Robey, chief of the craniofacial and skeletal diseases branch of the National Institute of Dental and Craniofacial Research, acknowledges the "promising" studies, but she has a different take on the importance of the cells.

"There are studies with dental pulp cells being used to treat neurological disorders and problems in the eye and other things," Robey said. The research is based on the idea that these cells "secrete factors that encourage local cells to begin the repair process."

"The problem is, these studies have really not been that rigorous," she said, adding that many have been done only in animals and so provide "slim" evidence of benefits. "The science needs a lot more work."

Robey would know. Her laboratory discovered dental stem cells in 2003.

"My fellows, Songtao Shi and Stan Gronthos, did the work in my lab," Robey said. "Songtao Shi is a dentist, and basically he observed that, when you get a cavity, you get what's called 'reparative dentin.' In other words, the tooth is trying to protect itself from that cavity, so it makes a little bit of dentin to kind of plug the hole, so to speak."

Dentin is the innermost hard layer of tooth that lies beneath the enamel. Underneath the dentin is a soft tissue known as pulp, which contains the nerve tissue and blood supply.

Observing dentin perform reparative work, Shi hypothesized that this must mean there's a stem cell within the tooth that's able to activate and make dentin. So if you wanted to grow an adult tooth instead of getting an implant, knowing how to make dentin would be the start of the process, explained Robey.

Pursuing this idea, Shi, Gronthos and the team conducted their first study with wisdom teeth. They discovered that pulp cells in these third molars did indeed make dentin, but the cells found in baby teeth, called SHED (stem cells from human exfoliated deciduous teeth), had slightly different properties.

"The SHED cells seem to make not only dentin but also something that is similar to bone," Robey said. This "dentin osteogenic material" is a little like bone and a little like dentin -- "unusual stuff," she said.

There is a meticulous process for extracting stem cells from the pulp.

"We very carefully remove any soft tissue that's adhering to the tooth. We treat it with disinfectant, because the mouth is not really that clean," Robey said, laughing.

Scientists then use a dental drill to pass the enamel and dentin -- "kind of like opening up a clam," said Robey -- to get to the pulp. "We take the pulp out, and we digest it with an enzyme to release the cells from the matrix of the pulp, and then we put the cells into culture and grow them."

According to Laning, even very small amounts of dental pulp are capable of producing many hundreds of millions of structural stem cells.

Harvesting dental stem cells is not a matter of waiting for the tooth to fall out and then quickly calling your dentist. When a baby tooth falls out, the viability of the pulp is limited if it's not preserved in the proper solution.

American Academy of Pediatric Dentistry President Dr. Jade Miller explained that "it's critical that the nerve tissue in that pulp tissue, the nerve supply and blood supply, still remain intact and alive." Typically, the best baby teeth to harvest are the upper front six or lower front six -- incisors and cuspids, he said.

For a child between 5 and 8 years of age, it's best to extract the tooth when there's about one-third of the root remaining, Miller said: "It really requires some planning, and so parents need to make this decision early on and be prepared and speak with their pediatric dentist about that."

Bassetto found the process easy. All it involved was a phone call to the company recommended by her dentist.

"They offer a service where they grow the cells and save those and also keep the pulp of the tooth without growing cells from it," she said. "I opted for both." From there, she said, the dentist shipped the extracted teeth overnight in a special package.

Bassetto said she paid less than $2,000 upfront, and now $10 a month for continued storage.

So is banking teeth something parents should be doing?

In a policy statement, the American Academy of Pediatric Dentistry "encourages dentists to follow future evidence-based literature in order to educate parents about the collection, storage, viability, and use of dental stem cells with respect to autologous regenerative therapies."

"Right now, I don't think it is a logical thing to do. That's my personal opinion," said Robey of the National Institute of Dental and Craniofacial Research. As of today, "we don't have methods for creating a viable tooth. I think they're coming down the pike, but it's not around the corner."

Science also does not yet support using dental pulp stem cells for other purposes.

"That's not to say that in the future, somebody could come up with a method that would make them very beneficial," Robey said.

Still, she observed, if science made it possible to grow natural teeth from stem cells and you were in a car accident, for example, and lost your two front teeth, you'd probably be "very happy to give up a third molar to use the cells in the molar to create new teeth." Third molars are fairly expendable, she said.

Plus, Robey explained, it may not be necessary to bank teeth: Another type of stem cell, known as induced pluripotent stem cells, can be programmed into almost any cell type.

"It's quite a different story than banking umbilical cord blood, which we do know contains stem cells that re-create blood," Robey said.

"So cord blood banking -- and now we have a national cord blood bank as opposed to private clinics -- so there's a real rationale for banking cord blood, whereas the rationale for banking baby teeth is far less clear," Robey said.

And there's no guarantee that your long-cryopreserved teeth or cells will be viable in the future. Banking teeth requires proper care and oversight on the part of cryopreservation companies, she said. "I think that that's a big question mark. If you wanted to get your baby teeth back, how would they handle that? How would they take the tooth out of storage and isolate viable cells?"

Provia's Laning, who has "successfully thawed cells that have been frozen for more than 30 years," dismissed such ideas.

"Cryopreservation technology is not the problem here," he said. "Stem cells from bone marrow and other sources have been frozen for future clinical use in transplants for more than 50 years. Similarly, cord blood has a track record of almost 40 years." The technology for long-term cryopreservation has been refined over the years without any substantial changes, he said.

Despite issues and doubts, Miller, of the pediatric dentistry academy, said parents still need to consider banking baby teeth.

A grandparent, he is making the decision for his own family.

"It's really at its infancy, much of this research," he said. "There's a very strong chance there's going to be utilization for these stem cells, and they could be life-saving."

He believes that saving baby teeth could benefit not only his grandchildren but also their older siblings and various other family members if their health goes awry and a stem cell treatment is needed.

"The science is strong enough to show it's not science fiction," Miller said. "There's going to be a significant application, and I want to give my grandkids the opportunity to have those options."

Aside from cost, Miller said there are other considerations: "Is this company going to be around in 30, 40 years?" he asked. "That's not an easy thing to figure out."

Having taken the leap, Bassetto doesn't worry.

"In terms of viability, you know, if something were to happen with the company, you could always get what's stored and move it elsewhere, so I felt I was protected that way," she said. She feels "pretty confident" with her decision and plans to store her grandchildren's baby teeth.

Still, she concedes that her circumstances may be rare.

"Not everybody's going to be touched by some kind of disease where it just hits home," Bassetto said. "For me, that made it a no-brainer."

Read the rest here:
Are baby, wisdom teeth the next wave in stem cell treatment? - CNN

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April 26th, 2017

Bone marrow drive for Allums siblings at ULM, other locations – Monroe News Star

By Dr. Matthew Watson

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A bone marrow drive for James Christopher Allums, 21, and his sister Elizabeth, 3, is Monday, May 1 at locations throughout northeast Louisiana.

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The News Star 11:33 a.m. CT April 26, 2017

University of Louisiana Monroe(Photo: Courtesy image)

A bone marrow drive for James Christopher Allums, 21, and his sister Elizabeth, 3, is Monday, May 1 at locations throughout northeast Louisiana.

University of Louisiana Monroe Medical Laboratory Science faculty and students are helping organize the drive. The drive on campus is 9 a.m.-5 p.m. in the SUB and Quad.

May 1 is National Fanconi Anemia Day. James Christopher and Elizabeth suffer from this disease, which is fatal without a bone marrow or stem cell transplant. They are the children of Chris and Ellen Allums.

Melanie Chapman, assistant professor to the School of Health Professions, said, "This is a wonderful opportunity for ULM Warhawks to fly high by working together and setting aside our busy agendas to give two great kids, and possibly others, the chance to live out their years. I am privileged to be a part of ULM and this community effort."

Bone marrow drive locations:

Times vary and new locations may be added. For information, check Facebook The Friends of James Christopher and Elizabeth Allums or visit caringbridge.org and search James Christopher Allums .

MORE NEWS;The Fabulous Equinox Orchestra takes the stage at ULM Friday

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Bone marrow drive for Allums siblings at ULM, other locations - Monroe News Star

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April 26th, 2017

Tough time: Jonathan Pitre battles kidney complications – Ottawa Sun

By raymumme

Ottawa Sun

Tough time: Jonathan Pitre battles kidney complications
Ottawa Sun
Pitre, 16, was infused two weeks ago with stem-cell rich blood and bone marrow drawn from his mother's hip. The procedure, conducted as part of an ongoing clinical trial at the University of Minnesota Masonic Children's Hospital, is the only treatment ...

and more »

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April 26th, 2017

TGF-/MAPK signaling mediates the effects of bone marrow mesenchymal stem cells on urinary control and interstitial … – UroToday

By NEVAGiles23

This study aimed to explore the role of the transforming growth factor-/mitogen activated protein kinase (TGF-/MAPK) signaling pathway in the effects of bone marrow mesenchymal stem cells (BMSCs) on urinary control and interstitial cystitis in a rat model of urinary bladder transplantation.

A urinary bladder transplantation model was established using Sprague-Dawley rats. Rats were assigned to normal (blank control), negative control (phosphate-buffered saline injection), BMSCs (BMSC injection), sp600125 (MAPK inhibitor injection), or protamine sulfate (protamine sulfate injection) groups. Immunohistochemistry, urodynamic testing, hematoxylin-eosin staining, Western blotting, enzyme-linked immunosorbent assay, and MTT assay were used to assess BMSC growth, the kinetics of bladder urinary excretion, pathological changes in bladder tissue, bladder tissue ultrastructure, the expression of TGF-/MAPK signaling pathway-related proteins, levels of inflammatory cytokines, and the effects of antiproliferative factor on cell proliferation.

Compared with normal, negative control, BMSCs, and sp600125 groups, rats in the PS group exhibited decreased discharge volume, maximal micturition volume, contraction interval, and bladder capacity but increased residual urine volume, bladder pressure, bladder peak pressure, expression of TGF-/MAPK signaling pathway-related proteins, levels of inflammatory cytokines, and growth inhibition rate. Levels of inflammatory cytokines and the growth inhibition rate were positively correlated with the expression of TGF-/MAPK signaling pathway-related proteins.

Our findings demonstrate that the TGF-/MAPK signaling pathway mediates the beneficial effects of BMSCs on urinary control and interstitial cystitis.

American journal of translational research. 2017 Mar 15*** epublish ***

Ya Xiao, Ya-Jun Song, Bo Song, Chi-Bing Huang, Qing Ling, Xiao Yu

Urological Research Institute of PLA, The First Affiliated Hospital, Third Military Medical UniversityChongqing 400037, P. R. China; Department of Urology, The Second Affiliated Hospital, The Third Military Medical UniversityChongqing 400037, P. R. China., Department of Urology, The Second Affiliated Hospital, The Third Military Medical University Chongqing 400037, P. R. China., Urological Research Institute of PLA, The First Affiliated Hospital, Third Military Medical University Chongqing 400037, P. R. China., Department of Urology, Tongji Hospital, Tongji Medical College of Huazhong University of Science & Technology Wuhan 430030, P. R. China.

PubMed http://www.ncbi.nlm.nih.gov/pubmed/28386345

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TGF-/MAPK signaling mediates the effects of bone marrow mesenchymal stem cells on urinary control and interstitial ... - UroToday

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April 26th, 2017

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