High-fat diet, obesity during pregnancy harms stem cells in developing fetus

Findings may provide broad context for the rise in immune disease and allergic disposition in children

PORTLAND, Ore. -- Physician-scientists at OHSU Doernbecher Children's Hospital reveal a high-fat diet and obesity during pregnancy compromise the blood-forming, or hematopoietic, stem cell system in the fetal liver responsible for creating and sustaining lifelong blood and immune system function.

The life-long burden of a western-style diet on the heart and circulatory system have long been appreciated. However, prior to this study, no one had considered whether the developing blood stem cells might be similarly vulnerable to prenatal high-fat diet and/or maternal obesity. The findings are published in the journal Molecular Metabolism.

"Our results offer a model for testing whether the effects of a high-fat diet and obesity can be repaired through dietary intervention, a key question when extrapolating this data to human populations," said Daniel L. Marks, M.D., Ph.D., co-investigator and professor of pediatric endocrinology in the OHSU School of Medicine and Pap Family Pediatric Research Institute at OHSU Doernbecher Children's Hospital.

Several years ago, Marks and colleagues developed a mouse model that closely mimics the high-fat, high-simple-sugar diet currently consumed by many young women of childbearing age. Their subsequent research demonstrated that maternal overnutrition in mice significantly reduced the size of the fetal liver.

Armed with this information, Marks partnered with another stem cell expert, Peter Kurre, M.D., co-investigator on the current study and professor of pediatric oncology in the OHSU School of Medicine and the Pap Family Pediatric Research Institute at OHSU Doernbecher Children's Hospital.

Together, they discovered that the complex changes that occur as a result of maternal high-fat diet and obesity put significant constraints on the growth and expansion of blood stem cells in the fetal liver, which ultimately compromises the developing immune system.

"In light of the spreading western-style, high-fat diet and accompanying obesity epidemic, this study highlights the need to better understand the previous unrecognized susceptibility of the stem and progenitor cell system," Kurre said. "These findings may provide broad context for the rise in immune disease and allergic disposition in children."

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The study, "Maternal high-fat diet and obesity compromise fetal hematopoiesis," was funded by Friends of Doernbecher and by the Oregon Clinical Translational Research Institute at OHSU. Research reported in this press release] was supported by National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR000128

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High-fat diet, obesity during pregnancy harms stem cells in developing fetus

Rudimentary egg and sperm cells made from stem cells

Southern Illinois University/Science photo Library

Some hope that sperm cells could one day be derived from the skin cells of a man who is otherwise sterile and that a similar process cold produce viable egg cells from a sterile woman's body.

Israeli and UK researchers have created human sperm and egg precursor cells in a dish, starting from a person's skin cells. The achievement is a small step towards a treatment for infertility, although one that could face significant controversy and regulatory hurdles.

The experiment, reported online in Cell on 24 December1, recreates in humans parts of a procedure first developed in mice, in which cells called induced pluripotent stem (iPS) cells reprogrammed cells that can differentiate into almost any cell type are used to create sperm or eggs that are subsequently manipulated to produce live births by in vitro fertilization.

In 2012, stem-cell biologist Mitinori Saitou of Kyoto University in Japan and his collaborators created the first artificial primordial germ cells (PGCs)2. These are specialized cells that emerge during embryonic development and later give rise to sperm or eggs. Saitou made them in a dish, starting with skin cells reprogrammed to an embryonic-like state through iPS-cell technology (see 'Stem cells: Egg engineers'). They also were able to achieve the same result starting with embryonic stem cells.

Although his cells could not develop beyond this precursor stage in the dish, Saito found that if he placed them in mouse testes, they would mature into sperm, and if he placed them in ovaries, they would mature into functional eggs. Both sperm and eggs could be used for in vitro fertilization.

Efforts to engineer similarly functional gametes in humans have produced PGC-like cells, but with such a low efficiency success rate of turning stem cells into gametes that it was difficult for others to expand on the work.. Previous efforts also required the introduction of genes that would render the cells unusable in the clinic.

Ewen Callaway reports on the ethical challenges of using lab-made sperm and egg cells in fertility treatments.

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Now a team led by Azim Surani of the University of Cambridge, UK, and Jacob Hanna of the Weizmann Institute of Science in Rehovot, Israel, has replicated the in vitro portion the first half, says Hanna of Saitous efforts in humans.

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Rudimentary egg and sperm cells made from stem cells

Stem Cell Cure: New Therapy For Joint Pain

DALLAS We all get those aches and pains every once in a while. But for some folks, those nagging aches are a pain in the well, you know.

My pain is a variety of different type of pain, David Flory said. In certain parts of the knee, certain types of activities bother it. some dont. Some do.

He has had knee problems since high school and has had five knee surgeries throughout his life.

Now his doctors have told him he needs a total knee replacement, but like a lot of people, Flory didnt want to go through the long recovery time that comes with going under the knife.

So in order to do that, Flory found a doctors office that offers stem cell replacement therapy.

Stem Cells are the type of cells that replicate and become other cells that are used in most healing, said Dr. Bill Johnson with Innovations Medical.

Basically what the doc does is take the stem cells from fat stored on your body, then inject that into the joint. This type of stem cell therapy is still being researched. Dr. Johnson says so far, 85% of knee patients have seen improvement.

Thats improvement to the point where they dont require joint replacement, Dr. Johnson said.

Since the procedure is still in the investigational stage, it isnt covered by insurance and can get a little pricey up to $6,000.

With the investment Im making out-of-pocket, Im hopeful what were doing today will pay off, said Flory.

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Stem Cell Cure: New Therapy For Joint Pain

Lansdowne author raises awareness about sickle cell disease

Dominique Friend doesn't look like she's sick. But the Lansdowne resident often deals with bouts of pain so severe she ends up in the hospital for weeks.

Friend, 44, was born with sickle cell disease, an inherited blood disorder that affects an estimated 90,000 to 100,000 in the U.S., according to Centers for Disease Control and Prevention information.

Her autobiography "Sickle" was released by Tate Publishing on Dec. 9 in a second edition, after she self-published the book in 2009.

In the book, she tells of her struggle with the debilitating disease. Friend said she shared her personal account to raise awareness about the disease, which predominantly affects African-Americans. It is also found in those of Hispanic and Mediterranean descent, according to CDC information.

Friend said for as long as she can recall, she has dealt with painful episodes that are characteristic of sickle cell disease.

Pain develops when sickle-shaped red blood cells, that should be round like a doughnut, block the blood flow to the chest, joints and other parts of the body, Friend explained. It can last for a few hours to a few weeks and such episodes are called "crises," she said.

"I would take the pain of childbirth over a sickle cell crisis any day," said Friend, who has three children, two stepdaughters and two granddaughters.

She has been married to Michael Friend for 18 years.

The painful disease can disrupt learning for children and make it difficult for adults to work, said Dr. Sophie Lanzkron, an assistant professor of medicine and oncology at Johns Hopkins University School of Medicine.

A bone marrow transplant or stem cell transplant is the only cure, according to the CDC website.

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Lansdowne author raises awareness about sickle cell disease

Iran opens cell therapy center

Source: ISNA

Iran inaugurated the cell therapy and regenerative medicine center affiliated to the country's Red Crescent Society in a ceremony attended by Iranian Vice President for Science and Technology Affairs Sorena Sattari.

"Stem cells are of great importance for the future. If we want to describe the modern medicine, we should say that one of its important bases is stem cell," he said.

He also said scientific projects take 10-15 years to turn into trade products.

In 2013, Iran hosted an international congress on stem cell and biomedicine attended by representatives of major medical research groups mostly from China, India, Italy and US and Iran have taken part in the two-day event and was organized by Iran's Royan institute.

The congress aimed to bring together the researchers and practitioners from all over the world in stem cells and reproductive biomedicine to stimulate and promote research in this area.

Stem cell research is one of the most promising research areas in modern biomedicine. However, due to moral and ethical debates, it remains a controversial issue in many regions of the world.

Stem cells have been shown to have significant capability to develop into a plethora of different cell types and work as a repair system to replenish cells with specialized functions.

Due to the efforts of Iranian scientists, doctors, engineers and researchers, Iran has advanced tremendously in the fields of stem cell research, medicine, nanotechnology, biotechnology and aerospace engineering.

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Iran opens cell therapy center

Adult Stem Cell Technology Center, LLCs Director Sherley's Address on Whats Holding Back Regenerative Medicine …

Boston, MA (PRWEB) December 23, 2014

Earlier this year in a June 24 international conference presentation, Dr. James L. Sherley, director of the Adult Stem Cell Technology Center, LLC (ASCTC) focused attention on an often overlooked and under appreciated unique property of adult tissue stem cells. His title Asymmetric Self-Renewal by Distributed Stem Cells: Misunderstood in the Past, Important for the Future, embodied the essence of his message to congress participants. He gave the address at the 4th World Congress on Cell Science and Stem Cell Research in Valencia, Spain.

The international congress was organized by the Omics Group as a part of its mission to foster the dissemination of leading discoveries and advances in life sciences research. Their posting this month of the slides from Dr. Sherley's June 24 keynote address now provides worldwide open access to life sciences investigators - stem cell biologists in particular - of the concepts that he emphasized.

In a 2008 publication [Breast Disease 29, 37-46, 2008], Sherley coined the new term distributed stem cells (DSCs) as a biology-based name for all natural tissue stem cells that are not embryonic in origin. Adult stem cells are included under the DSC heading. DSCs do not make every cell in the body. Their nature is to produce only a limited tissue-specific or organ-specific distribution of the total possible mature cell types. So, for example, liver DSCs make mature liver cells, but not mature cells found in other organs like the lungs.

Since 2001 and the start of "the stem cell debate," Sherley has insisted that only DSCs can be effective for developing new cellular therapies. In his keynote address, he explained to attendees why the counterparts of DSCs human embryonic stem cells (hESCs) and more recently developed induced pluripotent stem cells (iPSCs) could not.

Though many stem cell scientists recognize and acknowledge the genetic defects, incomplete differentiation, and tumor formation problems of hESCs and iPSCs - which their proponents suggest can be solved - few appreciate their greater problem, which cannot be solved. Unlike DSCs, hESCs and iPSCs lack the property of asymmetric self-renewal.

Sherleys main message is that asymmetric self-renewal, which is the gnomonic for DSCs the very property that defines DSCs is essential for effective cellular therapies. Asymmetric self-renewal means that DSCs can actively multiply with simultaneous reproduction of themselves and production of mature cells. This ability allows DSCs to replenish mature cells, which are continuously lost from tissues and organs, but not lose their genetic blueprint required for tissue and organ renewal and repair.

The asymmetric self-renewal of DSCs is a crucial consideration for all aspects of their study and use. Sherley argues that overlooking it is holding back progress in regenerative medicine. Asymmetric self-renewal is the factor that limits the production of DSCs; but it is so unique to them that it can also be used to identify DSCs, which are notorious for being elusive. The ASCTCs patented technologies for producing and counting DSCs for research and clinical development are grounded in the companys special research and bioengineering expertise for DSC asymmetric self-renewal.

Asymmetric self-renewal may even play a role in the efficient production of iPSCs. At the end of his address, Sherley announced the approval of a new ASCTC patent. The patent covers the invention of a method to make iPSCs from DSCs that were produced by regulating their asymmetric self-renewal (U.S. Patent and Trademark Office No. 8,759,098).

The ASCTC anticipates that despite the new technologys origin in DSC research, it will advance human disease research based on iPSCs. Although iPSCs are not suitable for cell therapy applications, they are uniquely able to provide disease research models for hard to obtain cell types found in patients (e.g., brain cells from autism patients, cardiac cells from heart disease patients).

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Adult Stem Cell Technology Center, LLCs Director Sherley's Address on Whats Holding Back Regenerative Medicine ...

Stem Cell Transplantation Centre Opens in Varna

A new stem cell transplantation centre opened on Monday in the St. Marina hospital in Varna, reports the bTV national channel.

It is the most up-to-date in Bulgaria and is expected to partially solve the shortage of such treatment of patients with oncological diseases.

According to the head of the heaematology clinic of the St. Marina hospital, Riana Gercheva, the stem cell treatment often is a life-saving procedure for cancer patients whose bone marrow has been severely damaged by chemotherapy.

According to the deputy rector of the Varna Medical University, Deyan Grancharov, there are two similar centres in Sofia and Plovdiv, but the demand was much higher. Now it will be much cheaper and easily accessible than similar treatment in Israel, for example, Grancharov said.

The capacity of the Varna centre is up to 100 patients per year. The procedure is free of charge for the insured.

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Stem Cell Transplantation Centre Opens in Varna

Test predicts response to treatment for complication of leukemia stem cell treatment

(New York City) A new test may reveal which patients will respond to treatment for graft versus host disease (GVHD), an often life-threatening complication of stem cell transplants (SCT) used to treat leukemia and other blood disorders, according to a study led by researchers at the Icahn School of Medicine at Mount Sinai and published online today in the journal Lancet Haematology and in print in the January issue.

Patients with fatal blood cancers like leukemia often require allogenic stem cell SCT to survive. Donor stem cells are transplanted to a recipient, but not without the risk of developing GVHD, a life-threatening complication and major cause of death after SCT. The disease, which can be mild to severe, occurs when the transplanted donor cells (known as the graft) attack the patient (referred to as the host). Symptom severity, however, does not accurately define how patients will respond to treatment and patients are often treated alike with high-dose steroids. Although SCT cures cancer in 50 percent of the patients, 25 percent die from relapsed cancer and there remaining go into remission but later succumb to effects of GVHD.

"High dose steroids is the only proven treatment for GVHD," said James L. M. Ferrara, MD, DSc, Ward-Coleman Chair in Cancer Medicine Professor at the Icahn School of Medicine at Mount Sinai, Director of Hematologic Malignancies Translational Research Center at Tisch Cancer Institute at Mount Sinai. "Those with low-risk GVHD are often over-treated and face significant side-effects from treatment. Patients with high risk GVHD are undertreated and the GVHD progresses, often with fatal consequences. Our goal is to provide the right treatment for each patient. We hope to identify those patients at higher risk and design an aggressive intervention while tailoring a less-aggressive approach for those with low-risk."

Dr. Ferrara, along with a multi-center team of researchers, developed and tested this new scoring system using almost 500 patient blood samples with newly diagnosed GVHD in varying grades from two different centers. They used three validated biomarkers TNFR1, ST2 and Reg3 to create an algorithm that calculated the probability of non-relapse mortality (usually caused by GVHD) that provided three distinct risk scores to predict the patient's response to GVHD treatment.

The acid test was to evaluate the algorithm in a validation set of 300 additional patients from twenty different SCT centers throughout the US. The algorithm worked perfectly, and the cumulative incidence of non-relapse mortality significantly increased as the GVHD score increased, and so the response rate to primary GVHD treatment decreased.

"This new scoring system will help identify patient who may not respond to standard treatments, and may require an experimental and more aggressive approach," said Dr. Ferrara. "And it will also help guide treatment for patients with lower-risk GVHD who may be over-treated. This will allow us to personalize treatment at the onset of the disease. Future algorithms will prove increasingly useful to develop precision medicine for all SCT patients."

In order to capitalize on this discovery, Dr. Ferrara has created the Mount Sinai Acute GVHD International Consortium (MAGIC) which consists of a group of ten SCT centers in the US and Europe who will collaborate to use this new scoring system to test new treatments for acute GVHD. Dr. Ferrara and colleagues have also written a protocol to treat high-risk GVHD that has been approved by the FDA.

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Co-collaborators included University of Michigan, University of Regensburg, and the Blood and Marrow Clinical Trials Network.

The study was supported by grants from the National Cancer Institute; the National Heart, Lung, and Blood Institute, the National Institute of Allergy and Infectious Diseases, the Doris Duke Charitable Fund, the American Cancer Society, and the Judith Devries Fund.

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Test predicts response to treatment for complication of leukemia stem cell treatment