Stem cell 'first aid' for rat stroke

27 January 2013 Last updated at 20:06 ET

Stem cells given in the vital period immediately after a stroke may aid recovery, suggest researchers.

Rats injected with stem cells 30 minutes after a stroke had almost normal brain function restored within a fortnight.

The Bolivian research team say the method has potential in human trials.

Current best practice is to treat many patients with "clot-busting" drugs in the "golden hour" after a stroke has taken place.

The research, published in the journal Stem Cell Research and Therapy, adds to others which have found that stem cells could aid stroke patients by boosting the body's ability to repair tissue damage.

Stem cells are the body's "master cells", with the potential to become many different cell types, and theoretically replace cells lost through disease or injury.

Recent tests in humans have show some promise, with stroke symptoms improving after an infusion of stem cells.

Stem cells are an incredibly interesting area of stroke research.

The Bolivian team, from La Paz University Hospital, extracted a certain type of stem cells from fat and bone marrow, then injected them into the blood vessels of rats shortly after they had suffered an artificially-induced stroke.

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Stem cell 'first aid' for rat stroke

Cardiac involvement and treatment-related mortality after non-myeloablative haemopoietic stem-cell transplantation …

Background

Autologous haemopoietic stem-cell transplantation (HSCT) benefits patients with systemic sclerosis but has been associated with significant treatment-related mortality and failure to improve diffusion capacity of carbon monoxide (DLCO). We aimed to assess efficacy of HSCT and use of rigorous cardiac screening in this group.

We assessed patients with diffuse systemic sclerosis or limited systemic sclerosis and interstitial lung disease who were treated with HSCT as part of a study or on a compassionate basis at Northwestern University (Chicago, IL, USA) or the University of So Paulo (Ribeiro Preto, Brazil). Unselected peripheral blood stem cells were harvested with cyclophosphamide (2 g/m2) and filgrastim. The transplant regimen was a non-myeloablative regimen of cyclophosphamide (200 mg/kg) and rabbit anti-thymocyte globulin (rATG; 4565 mg/kg). We followed patients up to 5 years for overall survival, relapse-free survival, modified Rodnan skin score, and pulmonary function tests.

Five (6%) of 90 patients died from treatment-related causes. Despite standard guidelines that recommend echocardiogram for screening before transplantation, four treatment-related deaths occurred because of cardiovascular complications (one constrictive pericarditis, two right heart failures without underlying infection, and one heart failure during mobilisation), and one death was secondary to sepsis without documented underlying heart disease. Kaplan-Meier analysis showed survival was 78% at 5 years (after eight relapse-related deaths) and relapse-free survival was 70% at 5 years. Compared with baseline, we noted improvements after HSCT in modified Rodnan skin scores at 1 year (58 patients; p<00001), 2 years (42 patients; p<00001), and 3 years (27 patients; p<00001) and forced vital capacity at 1 year (58 patients; p=0009), 2 years (40 patients; p=002), and 3 years (28 patients; p=0004), but total lung capacity and DLCO were not improved significantly after HSCT. Overall mean DLCO was significantly improved in patients with normal baseline echocardiograms (p=0005) or electrocardiographs (p=005).

Autologous HSCT with a non-myeloablative regimen of cyclophosphamide and rATG with a non-selected autograft results in sustained improvement in skin thickness and forced vital capacity. DLCO is affected by baseline cardiac function. Guidelines for cardiac screening of patients with systemic sclerosis to assess treatment-related risk from pulmonary artery hypertension, primary cardiac involvement, or pericardial disease should be reconsidered and updated.

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Cardiac involvement and treatment-related mortality after non-myeloablative haemopoietic stem-cell transplantation ...

Stem Cell Research: Stem Cells Nearly Cure Rats of Stroke Complications

The latest in stem cell research suggests that stem cells given in the vital period immediately after a stroke (known colloquially as the "golden hour") could make major headway in recovery. A research team in Bolivia injected rats with stem cells thirty minutes after a stroke, and discovered that they had almost completely normal brain function restored within two weeks. The team says that this has serious potential in human trials. Their study was led by Dr. Exuperio Diez-Tejedor from La Paz University Hospital, and supports previous studies that point in a similar direction: stem cells can be useful in treating stroke patients because they aid the body's ability to repair tissue damage. The stem cells used in this study were multipotent stromal cells extracted from fat and bone marrow. These are the types of stem cells that people are talking about when they talk of "master cells," the kind that can differentiate into many different cell types. Researchers hope that they will ultimately replace cells that are lost through disease or injury. The Bolivian study was published in the open-access journal Stem Cell Research and Therapy.

The controversy surrounding stem cells, at least in the United States, has been primarily centered around embryonic stem cells; but in this study, Dr. Diez-Tejedor was able to use "allogenic" (foreign) cells from other rats, and stated: "Improved recovery was seen regardless of origin of the stem cells, which may increase the usefulness of this treatment in human trials. Adipose (fat)-derived cells in particular are abundant and easy to collect without invasive surgery." This is outstanding news, as it implies that further research can be done and treatments be created without the destruction of embryos, effectively removing the politics from this branch of medicine. The team seems incredibly optimistic about their results, stating that they believe they might even be able to stop the "chain reaction" of cellular damage that results when the initial injury destroys cells in the surrounding areas. They continued, "From the viewpoint of clinical translation allogenic stem cells are attractive because they can be easily obtained from young healthy donors, amplified, and stored for immediate use when needed after a stroke." This implies that the usage of adult stem cells collected in a similar manner to that of a blood drive could ultimately provide a stroke treatment that would be immediately available to a suffering patient, just like donor blood. As exciting as this is, Dr. Clare Walton of the British organization The Stroke Association put a gentle damper on the enthusiasm, telling BBC News that human trials will not be happening anytime soon: "Stem cells are an incredibly interesting area of stroke research and the results of this study provide further insight into their potential use for stroke recovery. However, we are a long way off these types of treatments being used in humans and a lot more research is needed."

Despite the payoff of studies such as this one being so far in the future, the data suggesting that adult stem cells could be so incredibly useful should be heartening for those who have been disappointed by the political interference in this branch of medical research to date.

Follow Lauren Moccio on Twitter @TheGrottoTweets for more commentary on news, entertainment & politics.

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Stem Cell Research: Stem Cells Nearly Cure Rats of Stroke Complications

Stem Cell Therapy Helps Stroke Victims Recover in Two Weeks

The rats completely recovered from a stroke within two weeks with stem cell therapy (Wiki Commons)

Stem cell therapy administered shortly after a stroke could significantly increase the sufferer's chance of a complete recovery.

When administered to rats within 30 minutes of suffering a stroke, the rodents made a full recovery within two weeks, a study showed.

The research, published in BioMed Central's open access journalStem Cell Research & Therapy, found that stem cells from the bone marrow of fat can improve the recovery of rats following a stroke.

Researchers at La Paz University Hospital found that treatment improved the amount of brain and nerve repair, as well as the animal's ability to complete tasks.

Rats were treated intravenously with stem cells half an hour after a stroke. In humans, such rapid response is known to dramatically improve the outcome of victims.

The researchers found improvements in the stem cell group within 24 hours of the treatment, compared to the control group.

The FAST response advertising campaign has aimed to increase awareness of symptoms. Facial and arm weakness and speech problems suggest it is time to call emergency services.

Human trials

A delay in treatment can result in death or long-term disabilities. A stroke occurs when the blood supply to part of the brain is cut off.

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Stem Cell Therapy Helps Stroke Victims Recover in Two Weeks

Stem cells aid recovery from stroke

Public release date: 27-Jan-2013 [ | E-mail | Share ]

Contact: Hilary Glover hilary.glover@biomedcentral.com 44-020-319-22370 BioMed Central

Stem cells from bone marrow or fat improve recovery after stroke in rats, finds a study published in BioMed Central's open access journal Stem Cell Research & Therapy. Treatment with stem cells improved the amount of brain and nerve repair and the ability of the animals to complete behavioural tasks.

Stem cell therapy holds promise for patients but there are many questions which need to be answered, regarding treatment protocols and which cell types to use. This research attempts to address some of these questions.

Rats were treated intravenously with stem cells or saline 30 minutes after a stroke. At 24 hours after stroke the stem cell treated rats showed a better functional recovery. By two weeks these animals had near normal scores in the tests. This improvement was seen even though the stem cells did not appear to migrate to the damaged area of brain. The treated rats also had higher levels of biomarkers implicated in brain repair including, the growth factor VEGF.

A positive result was seen for both fat (adipose) and bone-marrow derived stem cells. Dr Exuperio Dez-Tejedor from La Paz University Hospital, explained, "Improved recovery was seen regardless of origin of the stem cells, which may increase the usefulness of this treatment in human trials. Adipose-derived cells in particular are abundant and easy to collect without invasive surgery."

###

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Dr Hilary Glover Scientific Press Officer, BioMed Central Mob: 44-778-698-1967

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Stem cells aid recovery from stroke

Stem cells aid recovery from stroke, study suggests

Jan. 28, 2013 Stem cells from bone marrow or fat improve recovery after stroke in rats, finds a study published in BioMed Central's open access journal Stem Cell Research & Therapy. Treatment with stem cells improved the amount of brain and nerve repair and the ability of the animals to complete behavioural tasks.

Stem cell therapy holds promise for patients but there are many questions which need to be answered, regarding treatment protocols and which cell types to use. This research attempts to address some of these questions.

Rats were treated intravenously with stem cells or saline 30 minutes after a stroke. At 24 hours after stroke the stem cell treated rats showed a better functional recovery. By two weeks these animals had near normal scores in the tests. This improvement was seen even though the stem cells did not appear to migrate to the damaged area of brain. The treated rats also had higher levels of biomarkers implicated in brain repair including, the growth factor VEGF.

A positive result was seen for both fat (adipose) and bone-marrow derived stem cells. Dr Exuperio Dez-Tejedor from La Paz University Hospital, explained, "Improved recovery was seen regardless of origin of the stem cells, which may increase the usefulness of this treatment in human trials. Adipose-derived cells in particular are abundant and easy to collect without invasive surgery."

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Stem cells aid recovery from stroke, study suggests

Stem cells aid recovery from stroke – Stem Cell Cafe

Jan 28

Public release date: 27-Jan-2013 [ | E-mail | Share ]

Contact: Hilary Glover hilary.glover@biomedcentral.com 44-020-319-22370 BioMed Central

Stem cells from bone marrow or fat improve recovery after stroke in rats, finds a study published in BioMed Centrals open access journal Stem Cell Research & Therapy. Treatment with stem cells improved the amount of brain and nerve repair and the ability of the animals to complete behavioural tasks.

Stem cell therapy holds promise for patients but there are many questions which need to be answered, regarding treatment protocols and which cell types to use. This research attempts to address some of these questions.

Rats were treated intravenously with stem cells or saline 30 minutes after a stroke. At 24 hours after stroke the stem cell treated rats showed a better functional recovery. By two weeks these animals had near normal scores in the tests. This improvement was seen even though the stem cells did not appear to migrate to the damaged area of brain. The treated rats also had higher levels of biomarkers implicated in brain repair including, the growth factor VEGF.

A positive result was seen for both fat (adipose) and bone-marrow derived stem cells. Dr Exuperio Dez-Tejedor from La Paz University Hospital, explained, Improved recovery was seen regardless of origin of the stem cells, which may increase the usefulness of this treatment in human trials. Adipose-derived cells in particular are abundant and easy to collect without invasive surgery.

###

Media Contact

Dr Hilary Glover Scientific Press Officer, BioMed Central Mob: 44-778-698-1967

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Stem cells aid recovery from stroke – Stem Cell Cafe

Experts urge caution when seeking stem cell treatments

ORLANDO, Fla. Boca Raton, Fla., parents Gary and Judy Susser say they know the hope and promise of stem-cell therapy. Nine years ago they traveled to Mexico for stem cell injections for their son Adam, who has cerebral palsy.

"Maybe it will do some good," Gary Susser said he and his wife thought at the time. They spent $25,000.

But the Sussers stopped stem cell injections in 2005, after spending about $25,000 and seeing no improvement. Today, armed with more information, the Sussers are grateful the treatments didn't harm Adam, now 12. While they are advocates of "responsible" stem cell research, they warn other parents against making trips to Costa Rica, Mexico, Russia or other offshore clinics for experimental treatments.

With promising breakthroughs making the news, as well as Internet hype, desperate parents and seriously ill patients may look to stem cell therapy as the modern miracle that could cure them. And one day, stem cells may be routinely used to repair damaged cells, improve the treatment of diseases and even cure paralysis.

But there are hidden dangers to today's stem cell treatments, both in the U.S. and offshore, scientists said at the recent World Stem Cell Summit in West Palm Beach, Fla. They pointed to reports of deaths, tumors, lumbar punctures and other potential harm, as well as vulnerable people being conned out of thousands of dollars.

Patients are "buying hope," said University of Miami scientist James Guest, working on The

Scientists urge consumers look for regulated clinical trials at universities and research institutions, saying that even those are not without risks.

"Clinics are operating out of loopholes, a gray area disguised as the practice of medicine," said George Q. Daley, director of the stem cell transplantation program at MI/Children's Hospital in Boston.

Industry researcher Douglas Sipp has kept records of more than 400 companies advertising stem cell products or procedures on websites since 2007. When he rechecked this summer, Sipp said, 80 of the sites were no longer online, though they could have simply changed web addresses.

Some of the offshore clinics have been closed by individual countries after patients died, according to Sipp, who leads the research unit for Science Policy and Ethics Studies at the RIKEN Center in Japan.

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Experts urge caution when seeking stem cell treatments

Study shows potential of differentiated iPS cells in cell therapy without immune rejection

A new study from Boston University School of Medicine (BUSM) shows that tissues derived from induced pluripotent stem (iPS) cells in an experimental model were not rejected when transplanted back into genetically identical recipients. The study, published online in Cell Stem Cell, demonstrates the potential of utilizing iPS cells to develop cell types that could offer treatment for a wide range of conditions, including diabetes, liver and lung diseases, without the barrier of immune rejection.

Ashleigh Boyd, DPhil, and Neil Rodrigues, DPhil, the study's senior authors, are assistant professors of dermatology at BUSM and researchers at the Center for Regenerative Medicine (CReM) at Boston University and Boston Medical Center (BMC). They also are lead investigators at the National Institutes of Health's Center of Biomedical Research Excellence (COBRE) at Roger Williams Medical Center, a clinical and research affiliate of BUSM.

iPS cells can be developed from adult cell types, such as skin or blood, by returning them to a stem cell state using genetic manipulation. iPS cells are capable of maturing (differentiating) into all the specific cell types in the body, making them a powerful tool for biological research and a source of tissues for transplantation based therapies. Given that iPS cells can be made in a patient-specific manner, there should be great potential for them to be transplanted back into the same patient without rejection. Yet a study published in Nature in 2011 demonstrated that iPS cells transplanted in the stem cell state were rejected in genetically identical recipients.

"The Nature study provocatively suggested that tissues derived from patient-specific iPS cells may be immunogenic after transplantation. However, it never directly assessed the immunogenicity of the therapeutically relevant cell types that could be utilized in regenerative medicine and transplantation," said Rodrigues.

The BUSM researchers evaluated this matter by taking adult cells from an experimental model and deriving iPS cells from them. They then differentiated the iPS cells into three cell types: neuronal (nerve); hepatocytes (liver); and endothelial (blood vessel lining) cells. These three cell types represent each of the three germ layers present during embryonic development mesoderm, ectoderm and endoderm. Cells from these layers differentiate and ultimately develop into the body's tissue and organ systems. Using experiments to mirror the potential clinical use of patient-specific iPS cells in cell therapy, the team transplanted each of the differentiated cells into a genetically identical experimental model and found no signs of an elevated immune response or indications of rejection.

The study results suggest that using patient-specific iPS cells should overcome issues of immune rejection in transplantation, which will be a significant problem for potential embryonic stem cell-derived therapies. Immune rejection in transplantation is treated clinically by immunosuppressive drugs but they can have serious side-effects, including the risk of developing cancer.

"If the use of immunosuppressive drugs can be avoided, as may be the case for patient-specific iPS cell based therapies, it would be preferable. Our results are very promising and future work should be directed at assessing whether tissues derived from human iPS cells will similarly lack immunogenicity," said Boyd.

Journal reference: Cell Stem Cell

Provided by Boston University Medical Center

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Study shows potential of differentiated iPS cells in cell therapy without immune rejection

Rush researchers studying stem cell therapy to repair damaged knee cartilage

Public release date: 24-Jan-2013 [ | E-mail | Share ]

Contact: Deb Song deb_song@rush.edu 312-942-0588 Rush University Medical Center

(CHICAGO) Rush University Medical Center is conducting the nation's first clinical study of an innovative stem cell drug, Cartistem, to repair knee cartilage damaged by aging, trauma or degenerative diseases such as osteoarthritis.

Cartistem is manufactured from mesenchymal stem cells derived from allogeneic (donor) umbilical cord blood. Umbilical cord blood is a readily accessible source of high-quality stem cells, is associated with minimal health risks and carries relatively few ethical concerns.

The stem cells are mixed with hyaluronan, a natural polymer that plays a major role in wound healing and is a building block of joint cartilage. Cartistem is surgically administered into the area of cartilage damage following an arthroscopic surgery as an adjunct to microfracture, a commonly used technique used to repair cartilage damage.

The principal investigator on the study is Dr. Brian Cole, a professor in the department of orthopedics and anatomy and cell biology at Rush University Medical Center. Dr. Cole is the head of Rush's Cartilage Restoration Center and is also the head team physician for the Chicago Bulls. Cole and his co-researchers will assess the drug's safety as well as its ability to regenerate cartilage repair tissue and reduce pain in patients with localized cartilage loss in the knee.

Treating cartilage damage can be problematic because the tissue does not contain blood vessels or nerves and therefore has a limited ability to re-grow. Various treatments for cartilage degeneration, such as drug therapy, arthroscopy and joint replacement, yield mixed results and are unable to regenerate damaged tissue.

"Finding a biological solution for cartilage regeneration in orthopedics is one of the fastest growing areas of research and development in our specialty, said Cole. "Rush is spearheading this field of research with the ultimate goal of safely improving outcomes and sparing patients from having more complicated surgery at a relatively young age."

The two-year, phase I/IIa study will enroll a total of 12 participants aged 18 years and older, with a body mass index of less than 35. Initially, six individuals with lesions sized 2 to 5 centimeters will be recruited into the study; an additional six volunteers with lesions larger than 5 centimeters will be enrolled sequentially. Each participant will undergo eligibility screening followed by a 12-month observation period to determine the safety and efficacy of the drug with an additional long-term follow-up evaluation at 24 months.

"With a burgeoning aging, yet active population, our patients are looking for effective non-joint replacement solutions to treat their damaged knee cartilage," said Cole. "This research is significant in that it utilizes a commonly performed operation (microfracture) in an effort to improve upon variable outcomes."

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Rush researchers studying stem cell therapy to repair damaged knee cartilage