Category Archives: Cell Medicine

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

(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

PHILADELPHIA As the main component of connective tissue in the body, fibroblasts are the most common type of cell. Taking advantage of that ready availability, scientists from the Perelman School of Medicine at the University of Pennsylvania, the Wistar Institute, Boston University School of Medicine, and New Jersey Institute of Technology have discovered a way to repurpose fibroblasts into functional melanocytes, the body's pigment-producing cells. The technique has immediate and important implications for developing new cell-based treatments for skin diseases such as vitiligo, as well as new screening strategies for melanoma. The work was published this week in Nature Communications.

The new technique cuts out a cellular middleman. Study senior author Xiaowei George Xu, MD, PhD, an associate professor of Pathology and Laboratory Medicine, explains, "Through direct reprogramming, we do not have to go through the pluripotent stem cell stage, but directly convert fibroblasts to melanocytes. So these cells do not have tumorigenicity."

Changing a cell from one type to another is hardly unusual. Nature does it all the time, most notably as cells divide and differentiate themselves into various types as an organism grows from an embryo into a fully-functional being. With stem cell therapies, medicine is learning how to tap into such cell specialization for new clinical treatments. But controlling and directing the process is challenging. It is difficult to identify the specific transcription factors needed to create a desired cell type. Also, the necessary process of first changing a cell into an induced pluripotent stem cell (iPSC) capable of differentiation, and then into the desired type, can inadvertently create tumors.

Xu and his colleagues began by conducting an extensive literature search to identify 10 specific cell transcription factors important for melanocyte development. They then performed a transcription factor screening assay and found three transcription factors out of those 10 that are required for melanocytes: SOX10, MITF, and PAX3, a combination dubbed SMP3.

"We did a huge amount of work," says Xu. "We eliminated all the combinations of the other transcription factors and found that these three are essential."

The researchers first tested the SMP3 combination in mouse embryonic fibroblasts, which then quickly displayed melanocytic markers. Their next step used a human-derived SMP3 combination in human fetal dermal cells, and again melanocytes (human-induced melanocytes, or hiMels) rapidly appeared. Further testing confirmed that these hiMels indeed functioned as normal melanocytes, not only in cell culture but also in whole animals, using a hair-patch assay, in which the hiMels generated melanin pigment. The hiMels proved to be functionally identical in every respect to normal melanocytes.

Xu and his colleagues anticipate using their new technique in the treatment of a wide variety of skin diseases, particularly those such as vitiligo for which cell-based therapies are the best and most efficient approach.

The method could also provide a new way to study melanoma. By generating melanocytes from the fibroblasts of melanoma patients, Xu explains, "we can screen not only to find why these patients easily develop melanoma, but possibly use their cells to screen for small compounds that can prevent melanoma from happening."

Perhaps most significantly, say the researchers, is the far greater number of fibroblasts available in the body for reprogramming compared to tissue-specific adult stem cells, which makes this new technique well-suited for other cell-based treatments.

The research was supported by the National Institutes of Health (R01-AR054593, P30-AR057217)

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Cutting Out the Cellular Middleman: New Technology Directly Reprograms Skin Fibroblasts For a New Role

Consider the relationship between an air traffic controller and a pilot. The pilot gets the passengers to their destination, but the air traffic controller decides when the plane can take off and when it must wait. The same relationship plays out at the cellular level in animals, including humans. A region of an animal's genome -- the controller -- directs when a particular gene -- the pilot -- can perform its prescribed function.

A new study by cell and systems biologists at the University of Toronto (U of T) investigating stem cells in mice shows, for the first time, an instance of such a relationship between the Sox2 gene which is critical for early development, and a region elsewhere on the genome that effectively regulates its activity. The discovery could mean a significant advance in the emerging field of human regenerative medicine, as the Sox2 gene is essential for maintaining embryonic stem cells that can develop into any cell type of a mature animal.

"We studied how the Sox2 gene is turned on in mice, and found the region of the genome that is needed to turn the gene on in embryonic stem cells," said Professor Jennifer Mitchell of U of T's Department of Cell and Systems Biology, lead invesigator of a study published in the December 15 issue of Genes & Development.

"Like the gene itself, this region of the genome enables these stem cells to maintain their ability to become any type of cell, a property known as pluripotency. We named the region of the genome that we discovered the Sox2 control region, or SCR," said Mitchell.

Since the sequencing of the human genome was completed in 2003, researchers have been trying to figure out which parts of the genome made some people more likely to develop certain diseases. They have found that the answers are more often in the regions of the human genome that turn genes on and off.

"If we want to understand how genes are turned on and off, we need to know where the sequences that perform this function are located in the genome," said Mitchell. "The parts of the human genome linked to complex diseases such as heart disease, cancer and neurological disorders can often be far away from the genes they regulate, so it can be dificult to figure out which gene is being affected and ultimately causing the disease."

It was previously thought that regions much closer to the Sox2 gene were the ones that turned it on in embryonic stem cells. Mitchell and her colleagues eliminated this possibility when they deleted these nearby regions in the genome of mice and found there was no impact on the gene's ability to be turned on in embryonic stem cells.

"We then focused on the region we've since named the SCR as my work had shown that it can contact the Sox2 gene from its location 100,000 base pairs away," said study lead author Harry Zhou, a former graduate student in Mitchell's lab, now a student at U of T's Faculty of Medicine. "To contact the gene, the DNA makes a loop that brings the SCR close to the gene itself only in embryonic stem cells. Once we had a good idea that this region could be acting on the Sox2 gene, we removed the region from the genome and monitored the effect on Sox2."

The researchers discovered that this region is required to both turn Sox2 on, and for the embryonic stem cells to maintain their characteristic appearance and ability to differentiate into all the cell types of the adult organism.

"Just as deletion of the Sox2 gene causes the very early embryo to die, it is likely that an abnormality in the regulatory region would also cause early embryonic death before any of the organs have even formed," said Mitchell. "It is possible that the formation of the loop needed to make contact with the Sox2 gene is an important final step in the process by which researchers practicing regenerative medicine can generate pluripotent cells from adult cells."

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Cell biologists discover on-off switch for key stem cell gene

As the main component of connective tissue in the body, fibroblasts are the most common type of cell. Taking advantage of that ready availability, scientists from the Perelman School of Medicine at the University of Pennsylvania, the Wistar Institute, Boston University School of Medicine, and New Jersey Institute of Technology have discovered a way to repurpose fibroblasts into functional melanocytes, the body's pigment-producing cells. The technique has immediate and important implications for developing new cell-based treatments for skin diseases such as vitiligo, as well as new screening strategies for melanoma. The work was published this week in Nature Communications.

The new technique cuts out a cellular middleman. Study senior author Xiaowei "George" Xu, MD, PhD, an associate professor of Pathology and Laboratory Medicine, explains, "Through direct reprogramming, we do not have to go through the pluripotent stem cell stage, but directly convert fibroblasts to melanocytes. So these cells do not have tumorigenicity."

Changing a cell from one type to another is hardly unusual. Nature does it all the time, most notably as cells divide and differentiate themselves into various types as an organism grows from an embryo into a fully-functional being. With stem cell therapies, medicine is learning how to tap into such cell specialization for new clinical treatments. But controlling and directing the process is challenging. It is difficult to identify the specific transcription factors needed to create a desired cell type. Also, the necessary process of first changing a cell into an induced pluripotent stem cell (iPSC) capable of differentiation, and then into the desired type, can inadvertently create tumors.

Xu and his colleagues began by conducting an extensive literature search to identify 10 specific cell transcription factors important for melanocyte development. They then performed a transcription factor screening assay and found three transcription factors out of those 10 that are required for melanocytes: SOX10, MITF, and PAX3, a combination dubbed SMP3.

"We did a huge amount of work," says Xu. "We eliminated all the combinations of the other transcription factors and found that these three are essential."

The researchers first tested the SMP3 combination in mouse embryonic fibroblasts, which then quickly displayed melanocytic markers. Their next step used a human-derived SMP3 combination in human fetal dermal cells, and again melanocytes (human-induced melanocytes, or hiMels) rapidly appeared. Further testing confirmed that these hiMels indeed functioned as normal melanocytes, not only in cell culture but also in whole animals, using a hair-patch assay, in which the hiMels generated melanin pigment. The hiMels proved to be functionally identical in every respect to normal melanocytes.

Xu and his colleagues anticipate using their new technique in the treatment of a wide variety of skin diseases, particularly those such as vitiligo for which cell-based therapies are the best and most efficient approach.

The method could also provide a new way to study melanoma. By generating melanocytes from the fibroblasts of melanoma patients, Xu explains, "we can screen not only to find why these patients easily develop melanoma, but possibly use their cells to screen for small compounds that can prevent melanoma from happening."

Perhaps most significantly, say the researchers, is the far greater number of fibroblasts available in the body for reprogramming compared to tissue-specific adult stem cells, which makes this new technique well-suited for other cell-based treatments.

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New technology directly reprograms skin fibroblasts for a new role

TORONTO A Canadian-led international team of researchers has begun solving the mystery of just how a specialized cell taken from a persons skin is reprogrammed into an embryonic-like stem cell, from which virtually any other cell type in the body can be generated.

The research is being touted as a breakthrough in regenerative medicine that will allow scientists to one day harness stem cells to treat or even cure a host of conditions, from blindness and Parkinsons disease to diabetes and spinal cord injuries.

Besides creating the reprogramming roadmap, the scientists also identified a new type of stem cell, called an F-class stem cell due to its fuzzy appearance. Their work is detailed in five papers published Wednesday in the prestigious journals Nature and Nature Communications.

Dr. Andras Nagy, a senior scientist at Mount Sinai Hospital in Toronto, led the team of 50 researchers from Canada, the Netherlands, South Korea and Australia, which spent four years analyzing and cataloguing the day-by-day process that occurs in stem cell reprogramming.

The work builds on the 2006-2007 papers by Shinya Yamanaka, who showed that adult skin cells could be turned into embryonic-like, or pluripotent, stem cells through genetic manipulation, a discovery that garnered the Japanese scientist the Nobel Prize in 2012.

Nagy likened the roughly 21-day process to complete that transformation to a black box, so called because scientists did not know what went on within the cells as they morphed from one cell type into the other.

It was just like a black box, Nagy said Wednesday, following a briefing at the hospital. You start with a skin cell, you arrive at a stem cell but we had no idea what was happening inside the cell.

Nagys team set about cataloguing the changes as they occurred by removing cells from culture dishes at set points during the three-week period, then analyzing such cellular material as DNA and proteins present at that moment.

The result is a database that will be available to scientists around the world, which the team hopes will spur new research to advance the field of stem cell-based regenerative medicine.

Co-author Ian Rogers, a scientist in Nagys lab, said the database will allow researchers to identify various properties of the developing stem cells, which could mean improving their ability to treat or cure disease.

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Researchers show how stem cells can be reprogrammed

Asymmetrex
Technologies For Stem Cell Medicine.

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Asymmetrex Stem Cell Medicine

By: Brad Cooper

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Asymmetrex Stem Cell Medicine - Video

Posted by Dana Sparks (@danasparks) 3 day(s) ago

Uniting the Global Stem Cell Community

The World Stem Cell Summit, December 3-5 in San Antonio, unites and educates the global stem cell community. With more than 1,200 attendees from more than 40 countries, the annual World Stem Cell Summits interdisciplinary agenda explores disease updates, research directions, cell standardization, regulatory pathways, reimbursements, financing, venture capital and economic development.

Throughout the week, the Mayo Clinic Center for Regenerative Medicine will use social media to connect using the hashtag #WSCS14. At the end of the week, we'll let the tweets, Google+ posts, Flickr photos, Facebook posts and YouTube videos tell the story.

The World Stem Cell Summit includes in-depth programming and more than 200 international speakers, including leaders from theMayo Clinic Center for Regenerative Medicine:

About the World Stem Cell SummitMayo Clinic, The University of Texas Health Science Center at San Antonio, Kyoto University Institute for Integrated Cell-Material Sciences (iCeMS), BioBridge Global, Baylor College of Medicine and the Regenerative Medicine Foundation have joined the Genetics Policy Institute to organize the10th Annual World Stem Cell Summit the largest and most comprehensive multi-track interdisciplinary stem cell conference.

Related LinksMayo Clinic at World Stem Cell Summit 2013Mayo Clinic at World Stem Cell Summit 2012

Regenerative MedicineWorld Stem Cell Summit

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Uniting the Global Stem Cell Community

SAN DIEGO--(BUSINESS WIRE)--Cytori Therapeutics, Inc. (NASDAQ: CYTX) today confirmed that two Japanese regenerative medicine laws, which went into effect on November 25, 2014, remove regulatory uncertainties and provide a clear path for the Company to commercialize and market Cytori Cell Therapy and its Celution System under the Companys existing and planned regulatory approvals.

Japans new regenerative medicine laws substantially clarify regulatory ambiguities of pre-existing guidelines and this news represents a significant event for Cytori, said Dr. Marc Hedrick, President & CEO of Cytori. We have a decade of operating experience in Japan and Cytori is nicely positioned to see an impact both on existing commercial efforts and on our longer-term efforts to obtain therapeutic claims and reimbursement for our products.

Under the two new laws, Cytori believes its Celution System and autologous adipose-derived regenerative cells (ADRCs) can be provided by physicians under current Class I device regulations and used under the lowest risk category (Tier 3) for many procedures with only the approval by accredited regenerative medicine committees and local agencies of the Ministry of Health, Labour and Welfare (MHLW). This regulatory framework is expected to streamline the approval and regulatory process and increase clinical use of Cytori Cell Therapy and the Celution System over the former regulations.

Before these new laws were enacted, the regulatory pathway for clinical use of regenerative cell therapy was one-size-fits-all, irrespective of the risk posed by certain cell types and approaches, said Dr. Hedrick. Now, Cytoris point-of-care Celution System can be transparently integrated into clinical use by providers under our Class I device status and the streamlined approval process granted to cell therapies that pose the lowest risk. Our technology is unique in that respect.

Cytoris Celution System Is in Lowest of Three Risk Categories

The Act on the Safety of Regenerative Medicines and an amendment of the 2013 Pharmaceutical Affairs Act (the PMD Act), collectively termed the Regenerative Medicine Laws, replace the Human Stem Cell Guidelines. Under the new laws, the cell types used in cell therapy and regenerative medicine are classified based on risk. Cell therapies using cells derived from embryonic, induced pluripotent, cultured, genetically altered, animal and allogeneic cells are considered higher risk (Tiers 1 and 2) and will undergo an approval pathway with greater and more stringent oversight due to the presumed higher risk to patients. Cytoris Celution System, which uses the patients own cells at the point-of-care, will be considered in the lowest risk category (Tier 3) for most cases, and will be considered in Tier 2 if used as a non-homologous therapy.

Streamlined Regulatory Approval for Certain Medical Devices

In the near future, Cytori intends to pursue disease-specific or therapeutic claims and reimbursement for Cytoris Celution System and the Company would, at that point, sponsor a clinical trial to obtain Class III device-based approval and reimbursement. The new laws include changes to streamline regulation of Class II and some Class III devices, which will now require the approval of certification bodies rather than the PMDA, similar to the European notified body model. To date, certification bodies have only been used for some Class II devices.

Conditional Regulatory Approval and Reimbursement Potential

As a supplementary benefit to Cytori, the Company may also choose to take advantage of the new conditional approval opportunities granted under the new laws. Once clinical safety and an indication of efficacy are shown, sponsors may apply for their cell product to receive conditional approval for up to seven years and may be eligible for reimbursement under Japans national insurance coverage. Under the conditional approval, the sponsor can then generate post-marketing data to demonstrate further efficacy and cost effectiveness.

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Cytori Expects New Japan Laws to Boost Adoption of Cytori Cell Therapy