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Stem cells derived from amniotic tissues have immunosuppressive properties

By Uncategorized

Japanese research also report the stem cells have effect on natural killer cells and monocyte function

Putnam Valley, NY. (Jan. 16th, 2015) - Stem cells derived from human amnion have for some time been considered promising for cell therapies because of their ease of access, ability to differentiate, and absence of ethical issues. Now, a Japanese research team has found that stem cells derived from human female amnion also have immunosuppressive activity and that the addition of antibodies to specific factors can enhance their immunosuppressive potential.

The study will be published in a future issue of Cell Transplantation and is currently freely available on-line as an unedited early e-pub at: http://www.ingentaconnect.com/content/cog/ct/pre-prints/content-CT-1273_Li_et_al.

The amniotic membrane is a tissue of fetal origin comprised of three layers. It is thought that there is a special immunologic mechanism protecting the fetus, so researchers were interested in finding out what immunological properties might reside in - and be extractable from - amnion cells.

"The human amniotic membrane contains both epithelial cells and mesenchymal cells," said study co-author Dr. Toshio Nikaido, Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences at the University of Toyama, Toyoma, Japan. "Both kinds of cells have proliferation and differentiation characteristics, making the amniotic membrane a promising and attractive source for amnion-derived cells for transplantation in regenerative medicine. It is clear that these cells have promise, although the mechanism of their immune modulation remains to be elucidated."

In this study, amnion-derived cells exerted an inhibitory effect on natural killer cells (NKs) and induced white blood cell activation. The researchers reported that the amnion-derived cells saw increases in interleukin-10 (IL-10).

"We consider that IL-10 was involved in the function of amnion-derived cells toward NK cells," explained Dr. Nikaido. "The immunomodulation of amnion-derived cells is a complicated procedure involving many factors, among which IL-10 and prostaglandin E2 (PGE2) play important roles."

Naturally occurring prostaglandins, such as PGE2, have important effects in labor and also stimulate osteoblasts to release factors that stimulate bone resorption by osteoclasts. PGE2 also suppresses T cell receptor signaling and may play a role in resolution of inflammation.

The use of antibodies against PGE2 and IL-10 removed the immunosuppressive effects of the amnion-derived cells by increasing natural killer cell cytotoxicity. This implies that these two factors are contributing elements to the immunosuppressive abilities of amnion-derived cells.

"Soluble factors IL-10 and PGE2 produced by amnion-derived cells may suppress allogenic, or "other" related immune responses," concluded Dr. Nikaido. "Our findings support the hypothesis that these cells have potential therapeutic use. However, further study is needed to identify the detailed mechanisms responsible for their immodulatory effects. Amnion-derived cells must be transplanted into mouse models for further in vivo analysis of their immunosuppressive activity or anti-inflammatory effects."

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Stem cells derived from amniotic tissues have immunosuppressive properties

Stem Cell Treatment Has UC Davis A Step Closer To HIV Cure

By Stem Cell Treatment

DAVIS (CBS13) Researchers at UC Davis say they are one step closer to finding a cure for HIV in a breakthrough study for millions around the world living with the virus.

At 60 years old, Paul Curtis looks like the picture of health.

I exercise, eat well get a lot of rest, he said.

But 30 years ago, Curtis was diagnosed as HIV-positive. Doctors told him he might have a year to live, but hes proven them wrong.

With this disease, its imperative that you take the medications consistently, Curtis said.

He relies on medication daily. At one point he took more than 40 pills a day. And he cant miss a dose.

The virus mutates rapidly when you miss doses, he said.

Hes one of millions worldwide waiting for a cure. Previous studies have come close, but none have proven to fight off the virus with stem cell therapy.

Dr. Joe Anderson says he has developed genetically modified human stem cells, which have resisted infection in mice.

When we infected the mice that had these HIV-resistant that had these HIV-resistant immune cells in them, we saw that HIV infection was blocked, he said.

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Stem Cell Treatment Has UC Davis A Step Closer To HIV Cure

Alberta MS patient says researcher was seen as 'some sort of god'

By Stem Cell Doctors

Winnipeg Free Press - ONLINE EDITION

By: Mary Agnes Welch

Posted: 01/15/2015 2:00 AM | Comments: | Last Modified: 01/15/2015 12:48 PM | Updates

CHRIS BOLIN / WINNIPEG FREE PRESS Enlarge Image

Lee Chuckry, who has MS, took part in a stem-cell trial run by Doug Broeska and Regenetek Research. The Airdrie, Alta., man eventually became one of Regenetek's most vocal critics. Photo Store

Before flying to India for experimental stem-cell therapy, Alberta businessman Lee Chuckry quit taking Tysabri, a drug many multiple-sclerosis patients use to shrink brain lesions and reduce attacks.

"It was quite effective for me," said Chuckry from his home in Airdrie, Alta. "I didnt have attacks when I was on it."

Doug Broeska, founder of Winnipeg-based Regenetek Research and the clinical trials principal investigator, told Chuckry that Tysabri would damage the effectiveness of the implanted stem cells.

Tysabri is one of a long list of medications Broeska advised clinical-trial participants to avoid, all mentioned in a blog posted last fall.

"My first attack started just when I was leaving India," said Chuckry. "Id stopped the drug three months before."

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Alberta MS patient says researcher was seen as 'some sort of god'

Alberta MS patient says researcher seen as 'some sort of god'

By Stem Cell Doctors

Winnipeg Free Press - PRINT EDITION

By: Mary Agnes Welch

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

BEFORE flying to India for experimental stem-cell therapy, Alberta businessman Lee Chuckry quit taking Tysabri, a drug many multiple-sclerosis patients use to shrink brain lesions and reduce attacks.

"It was quite effective for me," said Chuckry from his home in Airdrie, Alta. "I didn't have attacks when I was on it."

Doug Broeska, founder of Winnipeg-based Regenetek Research and the clinical trial's principal investigator, told Chuckry that Tysabri would damage the effectiveness of the implanted stem cells.

Tysabri is one of a long list of medications Broeska advised clinical-trial participants to avoid, all mentioned in a blog posted last fall.

"My first attack started just when I was leaving India," said Chuckry. "I'd stopped the drug three months before."

Chuckry knew Broeska was not a physician, but believed Broeska had a PhD and was a bona fide health researcher. Chuckry felt no better after the $24,000 stem-cell therapy. He became increasingly skeptical of Broeska and Regenetek when he returned home from India in May 2013 -- his MS just as bad, if not worse.

Chuckry spent 10 days trying to get in touch with Broeska to find out whether going back on his MS medication, this time a steroid called prednisone, would interfere with the effectiveness of his newly implanted stem cells. He could not get an answer from Broeska for days, and said there was no real followup care typically seen in a proper clinical trial -- no MRIs, no examination by a physician, no tests, no questionnaires.

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Alberta MS patient says researcher seen as 'some sort of god'

Treating non-healing bone fractures with stem cells

By Stem Cell Medicine

UC Davis to test device that offers new approach to obtaining stem cells during surgery

(SACRAMENTO, Calif.) -- A new device that can rapidly concentrate and extract young cells from irrigation fluid used during orthopaedic surgery holds promise for improving the delivery of stem cell therapy in cases of non-healing fractures. UC Davis surgeons plan to launch a "proof-of-concept" clinical trial to test the safety and efficacy of the device in the coming months.

"People come to me after suffering for six months or more with a non-healing bone fracture, often after multiple surgeries, infections and hospitalizations," said Mark Lee, associate professor of orthopaedic surgery, who will be principal investigator of the upcoming clinical trial. "Stem cell therapy for these patients can be miraculous, and it is exciting to explore an important new way to improve on its delivery."

About 6 million people suffer fractures each year in North America, according to the American Academy of Orthopaedic Surgeons. Five to 10 percent of those cases involve patients who either have delayed healing or fractures that do not heal. The problem is especially troubling for the elderly because a non-healing fracture significantly reduces a person's function, mobility and quality of life.

Stem cells - early cells that can differentiate into a variety of cell types - have been used for several years to successfully treat bone fractures that otherwise have proven resistant to healing. Applied directly to a wound site, stem cells help with new bone growth, filling gaps and allowing healing and restoration of function. However, obtaining stem cells ready to be delivered to a patient can be problematic. The cells ideally come from a patient's own bone marrow, eliminating the need to use embryonic stem cells or find a matched donor.

But the traditional way of obtaining these autologous stem cells - that is, stem cells from the same person who will receive them - requires retrieving the cells from a patient's bone marrow, a painful surgical procedure involving general anesthesia, a large needle into the hip and about a week of recovery.

In addition, the cells destined to become healing blood vessels must be specially isolated from the bone marrow before they are ready to be transplanted back into the patient, a process that takes so long it requires a second surgery.

The device Lee and his UC Davis colleagues will be testing processes the "wastewater" fluid obtained during an orthopaedic procedure, which makes use of a reamer-irrigator-aspirator (RIA) system to enlarge a patient's femur or tibia by high-speed drilling, while continuously cooling the area with water. In the process, bone marrow cells and tiny bone fragments are aspirated and collected in a filter to transplant back into the patient. Normally, the wastewater is discarded.

Although the RIA system filter captures the patient's own bone and bone marrow for use in a bone graft or fusion, researchers found that the discarded effluent contained abundant mesenchymal stem cells as well as hematopoietic and endothelial progenitor cells, which have the potential to make new blood vessels, and potent growth factors important for signaling cells for wound healing and regeneration. The problem, however, was that the RIA system wastewater was too diluted to be useful.

Now, working with a device developed by SynGen Inc., a Sacramento-based biotech company specializing in regenerative medicine applications, the UC Davis orthopaedic team will be able to take the wastewater and spin it down to isolate the valuable stem cell components. About the size of a household coffee maker, the device will be used in the operating room to rapidly produce a concentration of stem cells that can be delivered to a patient's non-union fracture during a single surgery.

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Treating non-healing bone fractures with stem cells

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

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