Stem Cell Clinic

Live imaging captures how blood stem cells take root in the body

By Stem Cell Medical Center

IMAGE:This image captures a blood stem cell en route to taking root in a zebrafish. view more

Credit: Boston Children's Hospital

BOSTON (January 15, 2015) -- A see-through zebrafish and enhanced imaging provide the first direct glimpse of how blood stem cells take root in the body to generate blood. Reporting online in the journal Cell today, researchers in Boston Children's Hospital's Stem Cell Research Program describe a surprisingly dynamic system that offers several clues for improving bone marrow transplants in patients with cancer, severe immune deficiencies and blood disorders, and for helping those transplants "take."

The steps are detailed in an animation narrated by senior investigator Leonard Zon, MD, director of the Stem Cell Research Program. The Cell version offers a more technical explanation

"The same process occurs during a bone marrow transplant as occurs in the body naturally," says Zon. "Our direct visualization gives us a series of steps to target, and in theory we can look for drugs that affect every step of that process."

"Stem cell and bone marrow transplants are still very much a black box--cells are introduced into a patient and later on we can measure recovery of their blood system, but what happens in between can't be seen," says Owen Tamplin, PhD, the paper's co-first author. "Now we have a system where we can actually watch that middle step. "

The blood system's origins

It had already been known that blood stem cells bud off from cells in the aorta, then circulate in the body until they find a "niche" where they're prepped for their future job creating blood for the body. For the first time, the researchers reveal how this niche forms, using time-lapse imaging of naturally transparent zebrafish embryos and a genetic trick that tagged the stem cells green.

On arrival in its niche (in the zebrafish, this is in the tail), the newborn blood stem cell attaches itself to the blood vessel wall. There, chemical signals prompt it to squeeze itself through the wall and into a space just outside the blood vessel.

"In that space, a lot of cells begin to interact with it," says Zon. Nearby endothelial (blood-vessel) cells wrap themselves around it: "We think that is the beginning of making a stem cell happy in its niche, like a mother cuddling a baby."

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Live imaging captures how blood stem cells take root in the body

Team isolates stem cell that gives rise to bones, cartilage in mice

By Stem Cell Medical Center

13 hours ago Hematopoietic precursor cells: promyelocyte in the center, two metamyelocytes next to it and band cells from a bone marrow aspirate. Credit: Bobjgalindo/Wikipedia

Researchers at the Stanford University School of Medicine have discovered the stem cell in mice that gives rise to bone, cartilage and a key part of bone marrow called the stroma.

In addition, the researchers have charted the chemical signals that can create skeletal stem cells and steer their development into each of these specific tissues. The discovery sets the stage for a wide range of potential therapies for skeletal disorders such as bone fractures, brittle bones, osteosarcoma or damaged cartilage.

A paper describing the findings will be published Jan. 15 in Cell.

"Millions of times a year, orthopedic surgeons see torn cartilage in a joint and have to take it out because cartilage doesn't heal well, but that lack of cartilage predisposes the patient to arthritis down the road," said Michael Longaker, MD, a professor of plastic and reconstructive surgery at Stanford and a senior author of the paper. "This research raises the possibility that we can create new skeletal stem cells from patients' own tissues and use them to grow new cartilage." Longaker is also co-director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine.

An intensive search

The researchers started by focusing on groups of cells that divide rapidly at the ends of mouse bones, and then showed that these collections of cells could form all parts of bone: the bone itself, cartilage and the stromathe spongy tissue at the center of bones that helps hematopoietic stem cells turn into blood and immune cells. Through extensive effort, they then identified a single type of cell that could, by itself, form all these elements of the skeleton.

The scientists then went much further, mapping the developmental tree of skeletal stem cells to track exactly how they changed into intermediate progenitor cells and eventually each type of skeletal tissue.

"Mapping the tree led to an in-depth understanding of all the genetic switches that have to be flipped in order to give rise to more specific progenitors and eventually highly specialized cells," said postdoctoral scholar Charles Chan, PhD, who shares lead authorship of the paper with postdoctoral scholar David Lo, MD, graduate student James Chen and research assistant Elly Eun Young Seo. With that information, the researchers were able to find factors that, when provided in the right amount and at the right time, would steer the development of skeletal stem cells into bone, cartilage or stromal cells.

"If this is translated into humans, we then have a way to isolate skeletal stem cells and rescue cartilage from wear and tear or aging, repair bones that have nonhealing fractures and renew the bone marrow niche in those who have had it damaged in one way or another," said Irving Weissman, MD, professor of pathology and of developmental biology, who directs the Stanford Institute for Stem Cell Biology and Regenerative Medicine. Weissman, the other senior author of the paper, also holds the Virginia and Daniel K. Ludwig Professorship in Clinical Investigation in Cancer Research.

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Team isolates stem cell that gives rise to bones, cartilage in mice

Stem-cell therapy clinic to open in Valley

By Stem Cell Clinic

The new clinic claims its stem-cell treatment can benefit those suffering from emphysema, chronic bronchitis, pulmonary fibrosis and most forms of lung disease.(Photo: Getty Images/iStockphoto)

The Lung Institute, a national clinic that uses adult stem cells extracted from fat and blood to treat pulmonary conditions, is set to open next month in Scottsdale, the for-profit company's first location in the western United States.

The new clinic claims its treatment can benefit those suffering from emphysema, chronic bronchitis, pulmonary fibrosis and most forms of lung disease.

Such stem-cell therapy is part of a growing trend particularly among affluent Americans who can afford it to treat a variety of health problems with cells taken from their own bodies.

The industry remains largely controversial, with plenty of doubters and detractors who say the science is unproven and potentially dangerous.

The International Society for Stem Cell Research, an independent non-profit organization based in Illinois, cautions against the potential risk of some treatments, which it says could cause cancer or result in infection from the procedure itself. The group suggests patients speak with their doctor about the potential benefits or risks of stem-cell therapy.

For its part, Lung Institute says the treatment helps fight lung conditions including chronic obstructive pulmonary disease, one of the world's leading killers. Cells extracted from one organ can create healthy tissue in another organ, the company claims.

The therapy is provided as an outpatient service, and patients can have cells drawn, isolated and planted in the affected area all in the same day. The clinic does not use embryonic, umbilical cord or donor stem cells.

Lung Institute, a clinic that uses stem cells to treat pulmonary conditions, is set to open its first West Coast location in Scottsdale in February 2015.(Photo: Courtesy of Lung Institute)

Patients typically visit the clinic for a few hours over three consecutive days. The treatment seeks to slow disease progression, calm inflammation or repair damaged tissue.

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Stem-cell therapy clinic to open in Valley

Stanford researchers isolate stem cell that gives rise to bones, cartilage in mice

By Uncategorized

Researchers at the Stanford University School of Medicine have discovered the stem cell in mice that gives rise to bone, cartilage and a key part of bone marrow called the stroma.

In addition, the researchers have charted the chemical signals that can create skeletal stem cells and steer their development into each of these specific tissues. The discovery sets the stage for a wide range of potential therapies for skeletal disorders such as bone fractures, brittle bones, osteosarcoma or damaged cartilage.

A paper describing the findings will be published Jan. 15 in Cell.

"Millions of times a year, orthopedic surgeons see torn cartilage in a joint and have to take it out because cartilage doesn't heal well, but that lack of cartilage predisposes the patient to arthritis down the road," said Michael Longaker, MD, a professor of plastic and reconstructive surgery at Stanford and a senior author of the paper. "This research raises the possibility that we can create new skeletal stem cells from patients' own tissues and use them to grow new cartilage." Longaker is also co-director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine.

An intensive search

The researchers started by focusing on groups of cells that divide rapidly at the ends of mouse bones, and then showed that these collections of cells could form all parts of bone: the bone itself, cartilage and the stroma -- the spongy tissue at the center of bones that helps hematopoietic stem cells turn into blood and immune cells. Through extensive effort, they then identified a single type of cell that could, by itself, form all these elements of the skeleton.

The scientists then went much further, mapping the developmental tree of skeletal stem cells to track exactly how they changed into intermediate progenitor cells and eventually each type of skeletal tissue.

"Mapping the tree led to an in-depth understanding of all the genetic switches that have to be flipped in order to give rise to more specific progenitors and eventually highly specialized cells," said postdoctoral scholar Charles Chan, PhD, who shares lead authorship of the paper with postdoctoral scholar David Lo, MD, graduate student James Chen and research assistant Elly Eun Young Seo. With that information, the researchers were able to find factors that, when provided in the right amount and at the right time, would steer the development of skeletal stem cells into bone, cartilage or stromal cells.

"If this is translated into humans, we then have a way to isolate skeletal stem cells and rescue cartilage from wear and tear or aging, repair bones that have nonhealing fractures and renew the bone marrow niche in those who have had it damaged in one way or another," said Irving Weissman, MD, professor of pathology and of developmental biology, who directs the Stanford Institute for Stem Cell Biology and Regenerative Medicine. Weissman, the other senior author of the paper, also holds the Virginia and Daniel K. Ludwig Professorship in Clinical Investigation in Cancer Research.

Reprogramming fat cells

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Stanford researchers isolate stem cell that gives rise to bones, cartilage in mice

Bone stem cells shown to regenerate bones and cartilage in adult mice

By Uncategorized

IMAGE:The osteochondroretricular stem cell, a newly identified type of bone stem cell that appears to be vital to skeletal development and may provide the basis for novel treatments for osteoarthritis,... view more

Credit: Laboratory of Dr. Timothy Wang

NEW YORK, NY (January 15, 2015) - A stem cell capable of regenerating both bone and cartilage has been identified in bone marrow of mice. The discovery by researchers at Columbia University Medical Center (CUMC) is reported today in the online issue of the journal Cell.

The cells, called osteochondroreticular (OCR) stem cells, were discovered by tracking a protein expressed by the cells. Using this marker, the researchers found that OCR cells self-renew and generate key bone and cartilage cells, including osteoblasts and chondrocytes. Researchers also showed that OCR stem cells, when transplanted to a fracture site, contribute to bone repair.

"We are now trying to figure out whether we can persuade these cells to specifically regenerate after injury. If you make a fracture in the mouse, these cells will come alive again, generate both bone and cartilage in the mouse--and repair the fracture. The question is, could this happen in humans," says Siddhartha Mukherjee, MD, PhD, assistant professor of medicine at CUMC and a senior author of the study.

The researchers believe that OCR stem cells will be found in human bone tissue, as mice and humans have similar bone biology. Further study could provide greater understanding of how to prevent and treat osteoporosis, osteoarthritis, or bone fractures.

"Our findings raise the possibility that drugs or other therapies can be developed to stimulate the production of OCR stem cells and improve the body's ability to repair bone injury--a process that declines significantly in old age," says Timothy C. Wang, MD, the Dorothy L. and Daniel H. Silberberg Professor of Medicine at CUMC, who initiated this research. Previously, Dr. Wang found an analogous stem cell in the intestinal tract and observed that it was also abundant in the bone.

"These cells are particularly active during development, but they also increase in number in adulthood after bone injury," says Gerard Karsenty, MD, PhD, the Paul A. Marks Professor of Genetics and Development, chair of the Department of Genetics & Development, and a member of the research team.

The study also showed that the adult OCRs are distinct from mesenchymal stem cells (MSCs), which play a role in bone generation during development and adulthood. Researchers presumed that MSCs were the origin of all bone, cartilage, and fat, but recent studies have shown that these cells do not generate young bone and cartilage. The CUMC study suggests that OCR stem cells actually fill this function and that both OCR stems cells and MSCs contribute to bone maintenance and repair in adults.

The researchers also suspect that OCR cells may play a role in soft tissue cancers.

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Bone stem cells shown to regenerate bones and cartilage in adult mice

Fallout from fake credentials

By Stem Cell Treatment

Winnipeg Free Press - PRINT EDITION

By: Mary Agnes Welch and Melissa Martin

Posted: 01/15/2015 3:00 AM | Comments:

The University of Winnipeg has axed a joint project with Regenetek Research, the local company selling stem-cell treatment to people with multiple sclerosis.

The move by the university's ethics committee came Wednesday, hours after the Free Press published its investigation into Regenetek owner Doug Broeska's credentials and his clinical trial.

The university's move puts an end to Broeska's repeated claim he was about to launch a study with U of W's kinesiology faculty to track and test some of the 70 patients who paid Regenetek as much as $45,000 for experimental stem-cell transplants in India.

"The patient outcomes have been so significant that we will soon be announcing a companion study with the University of Winnipeg," Broeska told a prospective patient in an email obtained by the Free Press. "Dr. Glen Bergeron, assistant dean and one of Canada's foremost physiotherapeutic specialists (head physiotherapist, Canadian Olympic Team) has confirmed our evidence based on patient observation... and would not have contemplated such a study if our patient/subjects had not demonstrated neural pathway restoration as a result of their therapies."

Winnipeg-based Regenetek and the U of W signed a preliminary letter of intent last spring. The company even gave the U of W $10,000 to hire a young researcher. She moved to Winnipeg from Waterloo, Ont., and began work in November in anticipation the joint research project would soon win ethics approval from the university's review panel.

Last week, the U of W's ethics committee sent the proposal back to Bergeron with questions and concerns. On Wednesday morning, the committee rejected the joint application outright.

Bergeron did not reply to requests for comment. Instead, Jino Distasio, the U of W's associate vice-president of research and innovation, said the university takes the health of study participants extremely seriously and already harboured concerns about the project.

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Fallout from fake credentials

U of W cancels proposal for joint research study

By Stem Cell Treatment

Winnipeg Free Press - ONLINE EDITION

By: Melissa Martin and Mary Agnes Welch

Posted: 01/15/2015 2:00 AM | Comments:

The University of Winnipeg has axed a joint project with Regenetek Research, the local company selling stem-cell treatment to people with multiple sclerosis.

The move by the universitys ethics committee came Wednesday, hours after the Free Press published its investigation into Regenetek owner Doug Broeskas credentials and his clinical trial.

The universitys move puts an end to Broeskas repeated claim he was about to launch a study with U of Ws kinesiology faculty to track and test some of the 70 patients who paid Regenetek as much as $45,000 for experimental stem-cell transplants in India.

"The patient outcomes have been so significant that we will soon be announcing a companion study with the University of Winnipeg," Broeska told a prospective patient in an email obtained by the Free Press. "Dr. Glen Bergeron, assistant dean and one of Canadas foremost physiotherapeutic specialists (head physiotherapist, Canadian Olympic Team) has confirmed our evidence based on patient observation... and would not have contemplated such a study if our patient/subjects had not demonstrated neural pathway restoration as a result of their therapies."

Winnipeg-based Regenetek and the U of W signed a preliminary letter of intent last spring. The company even gave the U of W $10,000 to hire a young researcher. She moved to Winnipeg from Waterloo, Ont., and began work in November in anticipation the joint research project would soon win ethics approval from the universitys review panel.

Last week, the U of Ws ethics committee sent the proposal back to Bergeron with questions and concerns. On Wednesday morning, the committee rejected the joint application outright.

Bergeron did not reply to requests for comment. Instead, Jino Distasio, the U of Ws associate vice-president of research and innovation, said the university takes the health of study participants extremely seriously and already harboured concerns about the project.

Continued here:
U of W cancels proposal for joint research study

New test helps guide treatment for bone marrow transplant patients with graft vs. host disease

By Stem Cell Doctors

Innovative scoring system uses 'Ann Arbor GVHD score' to better predict how patients will respond, minimize side effects

ANN ARBOR, Mich. - A new test can guide treatment for patients with graft versus host disease (GVHD), an often life-threatening complication of bone marrow and stem cell transplants, according to research from the University of Michigan published in Lancet Haematology this month.

Patients with fatal blood cancers like leukemia often need bone marrow or stem cell transplants to survive. But one of the most common and serious side effects that patients face is graft vs. host disease: when a patient's new immune system from the transplant (the graft) attacks the patient's healthy tissue (the host).

Most GVHD starts out as mild, but in two-thirds it eventually becomes severe. The treatment for severe GVHD is high doses of medications that knock out the immune system. But doctors have to be careful with drugs that further weaken a newly transplanted immune system, because they increase the risk for serious and life-threatening infections. Until now there has been no test to determine which cases of GVHD will become severe, so treatment is often delayed until the GVHD worsens.

The study's lead author, John Levine, M.D., of the University of Michigan's Blood and Marrow Transplant Program and his colleagues studied almost 800 patients from the US and Germany to develop and validate a new scoring system. The Ann Arbor GVHD score uses the levels of three proteins in the blood (TNFR1, ST2, and REG3a) to determine whether the patient should be treated right away or not and how intense the treatment should be. Patients with Ann Arbor 1 GVHD usually don't need treatment while patients with Ann Arbor 3 GVHD often don't respond to standard treatment and should be considered for clinical trials.

"We often have to treat all patients with GVHD alike with very high-dose steroids, because the severity of symptoms at the disease's onset don't help us predict how sick the patient will get. But this new scoring system will help identify patients that need a different approach, says Levine, who also is clinical director of the Pediatric Blood and Marrow Transplantation program at C.S. Mott Children's Hospital.

"And it can help us with patients with lower-risk GVHD who we may be over-treating. These scores can help us find a better, more individualized fit for our patients as soon as their disease is diagnosed," says Levine, who is professor of pediatrics at the University of Michigan Medical School.

Around half of patients who get a bone marrow transplant will develop GVHD, which can be lethal if it can't be controlled.

"Our goal is to offer personalized care. Doctors have struggled with individualizing therapy for each patient, but there's been no new therapy for GVHD in more than 40 years. So this new scoring system gives us another tool to better take care of our patients," Levine says.

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New test helps guide treatment for bone marrow transplant patients with graft vs. host disease

New device allows for manipulation of differentiating stem cells

By Stem Cell Medicine

Electroporation is a powerful technique in molecular biology. By using an electrical pulse to create a temporary nanopore in a cell membrane, researchers can deliver chemicals, drugs, and DNA directly into a single cell.

But existing electroporation methods require high electric field strengths and for cells to be suspended in solution, which disrupts cellular pathways and creates a harsh environment for sensitive primary cells. This makes it nearly impossible for researchers to study the cells naturally, in a setting that encourages the cells to continue differentiating and expanding.

A Northwestern University collaboration has developed a novel microfluidic device that allows for electroporation of stem cells during differentiation, making it possible to deliver molecules during this pivotal time in a cell's life. This provides the conditions needed to study primary cells, such as neurons, opening doors for exploration of the pathogenic mechanisms of neural diseases and potentially leading to new gene therapies.

Developed by Horacio Espinosa, the James and Nancy Farley Professor of Manufacturing and Entrepreneurship at the McCormick School of Engineering, and John Kessler, the Ken and Ruth Davee Professor of Stem Cell Biology at the Feinberg School of Medicine, the localized electroporation device (LEPD) can be applied to adherent cells, which are grown on an artificial substrate as opposed to free-floating in a culture medium and are able to continue growing and differentiating.

"The ability to deliver molecules into adherent cells without disrupting differentiation is needed for biotechnology researchers to advance both fundamental knowledge and the state-of-the-art in stem cell research," Espinosa said.

"Non-destructive manipulation of cells over time and in the correct environment is a key enabling technology highly needed within the biology and medical research communities," Kessler said.

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Supported by the National Science Foundation and the National Institutes of Health, the research is described in a paper published in the September 10 issue of Lab on a Chip, the journal of The Royal Society of Chemistry, and was also highlighted on the journal's back cover. Other authors on the paper include Wonmo Kang, Juan P. Giraldo-Vela, Shiva Nathamgari, Tammy McGuire, and Rebecca McNaughton.

The team fabricated the LEPD by employing a commonly used polymer for rapid prototyping of microfluidic devices for biological applications. It consists of circulation microchannels beneath a cell culture chamber made up of a perforated substrate and built-in electrodes. Although the main applications of the initial research examined neurons, the device is a general tool that can be used for any type of adherent cell.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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New device allows for manipulation of differentiating stem cells

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