Stem Cell Clinic

Sanger maps unique route to stem cells

Cambridge researchers have developed a new method to produce stem cells using designed proteins.

Stem cells have the potential to be used to replace dying or damaged cells with healthy cells. This repair could have wide-ranging uses in medicine such as organ replacement, bone replacement and treatment of neurodegenerative diseases. This study brings closer to realising the full potential of stem cell technology.

We have gone down a completely different road to standard practices to produce stem cells from adult cells, says Dr Pentao Liu, senior author from the Wellcome Trust Sanger Institute.

Current techniques to reprogramme cells are inefficient and its imperative to find other ways to create stem cells. We hope that our novel approach to reprogramming cells into stem cells will become a new and safer alternative to current practices.

The team looked at proteins called transcription factors, which regulate the activity of all human genes. Each transcription factor acts to modify the activity of several or many genes.

A key set of these transcription factors are able to convert or reprogramme adult cells into induced pluripotent stem cells or iPS cells. However, these factors also act on many genes other than those involved in reprogramming.

The team developed artificial designer transcription factors to target those key reprogramming genes more accurately, minimising activity on other genes.

"This is a promising and exciting development in our attempt to produce iPS cells that lend themselves in practical applications, says Dr Xuefei Gao, first author from the Wellcome Trust Sanger Institute. We have shown that targeting gene-control regions, called enhancers, in this structured way is a very effective in controlling a gene and reprogramming cells to become iPS cells.

In conventional methods, the transcription factors used to programme cells take part in complicated ways and target many different parts of the genome as they are used to reprogramme the cells to become stems cells. As a result, the throughput of successfully reprogrammed cells can be low and the additional number of steps can have associated risks, such as affecting genes that can influence tumour development.

The designer transcription factors are extremely accurate. Because this method targets key genes directly and avoids additional genetic detours, it reduces the potential risks linked with standard practices.

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Sanger maps unique route to stem cells

Sacramento startup gets FDA approval to sell stem cell therapy products

SynGen Inc., the midtown Sacramento medical device startup that develops stem cell harvesting systems, announced today that it has received U.S. Food and Drug Administration clearance to market three related products to process cord blood.

All three products are related to the company's SynGenX-1000 system, which harvests stem and progenitor cells from units of collected cord blood.

The company says harvested cells can be used for treatment of numerous medical conditions, including leukemia, lymphoma and more than 70 genetic diseases.

"We thank the FDA for guiding us through the ... clearance process. SynGen is dedicated to developing products that consistently exceed our customers' expectations," said Philip Coelho, company president and CEO.

Last year, SynGen received $5 million from San Francisco venture capital firm Bay City Capital LLC to further develop what Coelho has called the next generation in stem cell harvesting systems.

SynGen recently received additional financing of up to $3 million from Bay City.

Noting the new financing, Coelho said "we look forward to providing U.S. cord blood banks with the competitive advantage they will enjoy by using our products."

The Sacramento company also said it has received certification to market products in Europe. SynGen's focus is the development and commercialization of medical systems that harvest stem and progenitor cells from umbilical cord blood, bone marrow, peripheral blood and other tissues.

Coelho is the founder and former CEO of Rancho Cordova-based ThermoGenesis Corp., leaving that company's board of directors in 2008. He co-founded SynGen in 2007.

For more details, see syngeninc.com.

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Sacramento startup gets FDA approval to sell stem cell therapy products

Can stem cells make the blind see again?

Ten patients suffering from retinitis pigmentosa have had their eyesight restoredincluding a woman who had only 17 percent of her vision left By Anne A. Jambora Philippine Daily Inquirer

MANELLE Jose (left) whose vision has been restored. Dr. Harvey Uy is part of a three-man team that tested stem cell therapy for vision restoration in retinis pigmentosa. ROMY HOMILLADA

Making the blind see may no longer be an outrageous feat encountered only in books. What was once labeled a miracle is now the subject of intense study by the scientific community. The key to restoring vision? Why, yes, stem cell therapy, of course.

The stem cell therapy that began in November 2011, while still limited to the cure of the inherited eye disease retinitis pigmentosa (RP), has already restored the eyesight of 10 subjects.

RP is a degenerative disease that has, until today, no known cure. It is the most common inheritable cause for blindness1.5 million people around the world are blind from it.

RP is a group of hereditary eye disorders that affects the retinas ability to respond to light, causing people to slowly lose their vision until they go completely blind.

For most people afflicted with RP, when the slow death of the retinal photoreceptor cells occurs, the peripheral vision gradually darkens until one is left with a tunnel vision. Over time, the tunnel vision becomes smaller until one day everything becomes completely dark, when blindness finally settles in.

The inevitable progress of the disease can begin in a persons teens, such that they become completely blind by the time they reach adulthood.

There is no other more devastating eye disease than retinitis pigmentosa, because they start off life with fairly good vision, said Dr. Harvey S. Uy, vice president of the Philippine Academy of Ophthalmology and research fellow in ophthalmology at the Research and Biotechnology Division of St. Lukes Medical Center.

100,000 Filipinos

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Can stem cells make the blind see again?

How stem cells increase libido and enhance looks

Stem cell therapy results in dramatic decrease in blood sugar, improved sleep, increased energy levels and shoulder mobility, and improved libido. But StemGenics says patients must be tested first if theyre up to it By Marge C. Enriquez Philippine Daily Inquirer

OPERATION room maintains hospital standards.

Sam Fernandez (not his real name), a businessman in his late 50s, who underwent stem cell treatment, excitedly called his doctor, about its immediate effects. Although the benefits were supposed to be visible six to eight weeks after the procedure, the patient felt like a young man again in six days.

His doctor gave him intravenous therapy, directly injecting stem cell on the shoulder to address the chronic pains and the penis for erectile dysfunction. Aside from the dramatic decrease in blood sugar, improved sleep, increased energy levels and shoulder mobility, the patient reported increased libido. He claimed he was getting woody (slang for erection) every day that his wife couldnt keep up with him.

As the age management medicine trend, there are many hospitals and aesthetic centers offering stem cell treatment at the average price of P1.2 to P1.4 million. Accredited by the Department of Health, StemGenics not only offers medical technology that is unique to the clinic but also procedures at a reasonable price range of P500,000.

Repairing tissues

Dr. Eduardo Santos, president of StemGenics, said that stem cell therapy is just one of the three aims of a health program: There is repair, maintain and defend, he said.

He explained: Maintenance is a function of exercise, nutritional supplement and hormone support. Defense is a function of guarding the body against cancer and infection. You boost the immune system. The repair is the stem cell procedure, our anchor service. The stem cell regenerates the tissues. You reintegrate the organs which need to be repaired.

Stem cells used for repair are found in the bone marrow, blood, fat or adipose tissues and in other parts of the body. These cells are stimulated upon getting alerts on injury or inflammation. Their task is to precipitate the healing process when the body is injured. They send proteins to control the inflammation and refresh new cells, and engage new growth proteins. These cells are exchanging regenerative signals within the environment.

After birth, we have 80 to 100 million stem cells, said Santos. Over time, they decrease. By mid-30s, the count is down to 25 million. You wont have enough to heal as fast as you were younger. That is when aging happens. That is why disease associated with aging comes inheart conditions, dementia, decreased function of kidney and liver.

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How stem cells increase libido and enhance looks

ANN ARBOR: University of Michigan breast cancer clinical trial looks at targeting cancer stem cells

ANN ARBOR A major reason that breast cancer returns after treatment and spreads to other parts of the body is that current chemotherapy and radiation treatments do not kill the cancer stem cells.

That premise provides the basis for a clinical trial open at the University of Michigan Comprehensive Cancer Center and two other sites testing a drug that has been found in laboratory studies to attack cancer stem cells. The drug, reparixin, will be used in combination with standard chemotherapy.

This is one of only a few trials testing stem cell directed therapies in combination with chemotherapy in breast cancer, says principal investigator Dr. Anne Schott, associate professor of internal medicine at the University of Michigan. Combining chemotherapy with stem cell therapy has the potential to lengthen remissions for women with advanced breast cancer.

Cancer stem cells are the small number of cells within a tumor that fuel its growth and spread.

The phase Ib study will test reparixin, which is taken orally, along with the chemotherapy drug paclitaxel in women with HER2-negative metastatic breast cancer. The study is primarily intended to test how patients tolerate this drug combination, but researchers will also look at how reparixin appears to be impacting markers for cancer stem cells and signs of inflammation. The study will also look at how effective this treatment combination is at controlling the cancer and impacting survival.

The clinical trial stems from laboratory research at U-M that identified a receptor called CXCR1 on the cancer stem cells that triggers growth of stem cells in response to inflammation and tissue damage. Adding reparixin to chemotherapy in laboratory studies specifically targeted and killed breast cancer stem cells by blocking CXCR1.

Mice treated with reparixin or the combination of reparixin and chemotherapy had dramatically fewer cancer stem cells than those treated with chemotherapy alone. In addition, reparixin-treated mice developed significantly fewer metastases than mice treated with chemotherapy alone.

FYI

According to the American Cancer Society, 234,580 Americans will be diagnosed with breast cancer this year and 40,030 will die from the disease.

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ANN ARBOR: University of Michigan breast cancer clinical trial looks at targeting cancer stem cells

More older patients receiving stem-cell transplants at KU Cancer Center

If Patti Kennicott had gotten her diagnosis 10 years earlier, she would have had only a few months to live, Joseph McGuirk says.

Kennicott, who lives in Ottawa, was 62 when she was diagnosed with acute myeloid leukemia in 2010. Ten years before, conventional wisdom among doctors would have been that she was too old to receive a stem-cell transplant to treat her cancer, and her chance of survival would have been slim.

But Kennicott, now 65, is still alive. She received a stem-cell transplant at the Kansas University Cancer Centers Blood and Marrow Transplant program in February 2011.

And thats no longer a rare outcome for someone her age. The KU BMT program now sees more transplant patients in their 60s, and even their 70s or 80s, than ever before, after recent research has shown that stem-cell transplants can indeed be safe for older people.

Things have changed a lot since McGuirk, the medical director for the BMT program, started in his field in the early 1990s.

Back then, he said, the two-year survival rate was about 5 percent for a 70-year-old who received Kennicotts diagnosis of AML.

It was terrible, every bit as bad as pancreas cancer, McGuirk said.

Back then, doctors assumed that the intensive chemotherapy and radiation that accompanied stem-cell transplants would be too much for elderly patients even though some blood-borne cancers, such as AML, are more common in older people.

But since about 2000, doctors at KU and elsewhere have found that stem-cell transplants were effective in treating those cancers even without those other intensive therapies, using donors stronger immune systems to destroy the cancer.

So by the time Kennicott got her diagnosis, transplants for patients 60 and older were commonplace at the KU Cancer Center.

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More older patients receiving stem-cell transplants at KU Cancer Center

Injecting iron supplement lets scientists track transplanted stem cells

July 12, 2013 A new, noninvasive technique for tracking stem cells after transplantation -- developed by a cross-disciplinary team of radiologists, chemists, statisticians and materials scientists at the Stanford University School of Medicine -- could help surgeons determine whether a procedure to repair injured or worn-out knees is successful.

The technique, described in a study to be published online July 12 in Radiology, relies on an imaging agent already approved by the U.S. Food and Drug Administration for an entirely different purpose: anemia treatment. Although this study used rodents, the approach is likely to be adapted for use in humans this fall as part of a clinical trial in which mesenchymal stem cells will be delivered to the site of patients' knee injuries. Mesenchymal stem cells are capable of differentiating into bone and cartilage, as well as muscle, fat and tendon, but not into the other cell types that populate the body.

Every year, arthritis accounts for 44 million outpatient visits and 700,000 knee-replacement procedures. But the early repair of cartilage defects in young patients may prevent further deterioration of the joint and the need for knee replacement later in life, said the study's senior author, Heike Daldrup-Link, MD, PhD, an associate professor of radiology and clinician who splits her time between research and treating pediatric patients.

Mesenchymal stem cells have been used with some success in cartilage-repair procedures. "These cells can be easily derived from bone marrow of patients who are going to undergo the knee-repair procedure," said Daldrup-Link, a member of the Molecular Imaging Program at Stanford. "And they can differentiate into the real-life tissues that compose our joints. But here, too, things can go wrong. The newly transferred cells might fail to engraft, or die. They might migrate away. They could develop into tissues other than cartilage, most commonly fibrous scar tissue."

Relatively few transplanted cells go the distance. The ability to monitor the cells' engraftment after they are deposited at a patient's knee-injury site is therefore essential. With the new technique, magnetic resonance imaging can visualize stem cells for several weeks after they have been implanted, giving orthopaedic surgeons a better sense of whether the transplantation was successful.

Until now, the only ways of labeling mesenchymal stem cells so that they could be noninvasively imaged have required their manipulation in the laboratory. Upon extraction, the delicate cells have to be given to lab personnel, incubated with contrast agents, spun in a centrifuge and washed and returned to the surgeons, who then transplant the cells into a patient.

The new technique involves labeling the cells before extraction, while they reside in the donor's bone marrow. For the study, lead authors Aman Khurana, MD, a postdoctoral scholar, and Fanny Chapelin, a research associate, injected ferumoxytol, an FDA-licensed anemia treatment composed of iron-oxide nanoparticles, into rats prior to extracting bone marrow from them. Then, after enriching the mixture for mesenchymal stem cells, the investigators injected it into the sites of knee injuries in recipient rats. They followed the implanted cells' progress for up to four weeks, comparing the results with those obtained both from cells labeled in laboratory dishes and from unlabeled cells.

Daldrup-Link and others previously have used ferumoxytol for stem-cell labeling in a dish. However, mesenchymal stem cells in a laboratory dish take up very little of this substance. Interestingly, the researchers showed in a series of experiments that, ensconced in donor rats' bone marrow, the same cells are avid ferumoxytol absorbers. Even several weeks after transplantation into the recipient rats' knees, the mesenchymal stem cells retain enough iron to provide a strong MRI signal.

The new labeling technique alleviates the risks of contamination introduced when cells are labeled via manipulations in a laboratory dish -- a major regulatory concern, said Daldrup-Link -- as well as of a substantial loss of the delicate cells due to their extensive manipulation. It also allows for the immediate transfer of cells from a patient's bone marrow to the site of that patient's own knee injury.

That makes the technique useful in an autologous transplantation procedure, in which cells are extracted from a patient for the purpose of being delivered to another site during the same surgery. Jason Dragoo, MD, associate professor of orthopaedic surgery at the medical school and head team physician for the Stanford football program, plans to initiate a clinical trial this autumn whereby patients in need of knee repair will be treated with mesenchymal stem cells taken from their own bone marrow.

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Injecting iron supplement lets scientists track transplanted stem cells

Injecting iron supplement lets Stanford scientists track transplanted stem cells

Public release date: 12-Jul-2013 [ | E-mail | Share ]

Contact: Bruce Goldman 650-725-2106 Stanford University Medical Center

STANFORD, Calif. A new, noninvasive technique for tracking stem cells after transplantation developed by a cross-disciplinary team of radiologists, chemists, statisticians and materials scientists at the Stanford University School of Medicine could help surgeons determine whether a procedure to repair injured or worn-out knees is successful.

The technique, described in a study to be published online July 12 in Radiology, relies on an imaging agent already approved by the U.S. Food and Drug Administration for an entirely different purpose: anemia treatment. Although this study used rodents, the approach is likely to be adapted for use in humans this fall as part of a clinical trial in which mesenchymal stem cells will be delivered to the site of patients' knee injuries. Mesenchymal stem cells are capable of differentiating into bone and cartilage, as well as muscle, fat and tendon, but not into the other cell types that populate the body.

Every year, arthritis accounts for 44 million outpatient visits and 700,000 knee-replacement procedures. But the early repair of cartilage defects in young patients may prevent further deterioration of the joint and the need for knee replacement later in life, said the study's senior author, Heike Daldrup-Link, MD, PhD, an associate professor of radiology and clinician who splits her time between research and treating pediatric patients.

Mesenchymal stem cells have been used with some success in cartilage-repair procedures. "These cells can be easily derived from bone marrow of patients who are going to undergo the knee-repair procedure," said Daldrup-Link, a member of the Molecular Imaging Program at Stanford. "And they can differentiate into the real-life tissues that compose our joints. But here, too, things can go wrong. The newly transferred cells might fail to engraft, or die. They might migrate away. They could develop into tissues other than cartilage, most commonly fibrous scar tissue."

Relatively few transplanted cells go the distance. The ability to monitor the cells' engraftment after they are deposited at a patient's knee-injury site is therefore essential. With the new technique, magnetic resonance imaging can visualize stem cells for several weeks after they have been implanted, giving orthopaedic surgeons a better sense of whether the transplantation was successful.

Until now, the only ways of labeling mesenchymal stem cells so that they could be noninvasively imaged have required their manipulation in the laboratory. Upon extraction, the delicate cells have to be given to lab personnel, incubated with contrast agents, spun in a centrifuge and washed and returned to the surgeons, who then transplant the cells into a patient.

The new technique involves labeling the cells before extraction, while they reside in the donor's bone marrow. For the study, lead authors Aman Khurana, MD, a postdoctoral scholar, and Fanny Chapelin, a research associate, injected ferumoxytol, an FDA-licensed anemia treatment composed of iron-oxide nanoparticles, into rats prior to extracting bone marrow from them. Then, after enriching the mixture for mesenchymal stem cells, the investigators injected it into the sites of knee injuries in recipient rats. They followed the implanted cells' progress for up to four weeks, comparing the results with those obtained both from cells labeled in laboratory dishes and from unlabeled cells.

Daldrup-Link and others previously have used ferumoxytol for stem-cell labeling in a dish. However, mesenchymal stem cells in a laboratory dish take up very little of this substance. Interestingly, the researchers showed in a series of experiments that, ensconced in donor rats' bone marrow, the same cells are avid ferumoxytol absorbers. Even several weeks after transplantation into the recipient rats' knees, the mesenchymal stem cells retain enough iron to provide a strong MRI signal.

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Injecting iron supplement lets Stanford scientists track transplanted stem cells