Human neural stem cells are derived via fluorescence-activated cell sorting (FACS) from donated fetal brain tissue. Credit: Hal X. Nguyen and Aileen J. Anderson

A new study in mice published in The Journal of Neuroscience details a potential therapeutic strategy that uses stem cells to promote recovery of motor activity after spinal cord injury.

The transplantation of neural stem cells could help promote repair of an injured spinal cord, but the interaction between donor cells and the resident cells that are part of the body's immune response to injury is not well understood.

Hal Nguyen, Aileen Anderson and colleagues found that mice receiving stem cells derived from donated human brain tissue required depletion of a specific population of immune cells in order to improve the mice's ability to walk along a glass plate. Although the donor cells survived equally when transplanted immediately or 30 days after injury, their location and cell type changed with time. These results suggest that immune cells populating the spinal cord at different time points after injury affect the ability of stem cells to promote functional recovery.

Human neural stem cell replicates itself during mitosis in vitro. Credit: Hal X. Nguyen and Aileen J. Anderson

Explore further: Stem cell scarring aids recovery from spinal cord injury

More information: "Systemic neutrophil depletion modulates the migration and fate of transplanted human neural stem cells to rescue functional repair," Journal of Neuroscience (2017). DOI: 10.1523/JNEUROSCI.2785-16.2017

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Using donor stem cells to treat spinal cord injury

Spinal Cord Stem Cells Comments Off on Using donor stem cells to treat spinal cord injury | September 3rd, 2017

CINCINNATI -- Ryan Custer tearfully thanked the community for their support at his prayer service Sunday.

I cant thank you guys enough, he said in front of a standing ovation at Elder High Schools Fieldhouse.

Custer, an Elder grad and Wright State freshman, suffered a traumatic spinal injury at a large party in April after he tried to jump into a shallow, makeshift pool.

Family and friends welcomed Custer home on Wednesday. He had been been recovering and undergoing therapy at University of Cincinnati Medical Center. He also traveled to Chicago to be considered for a stem cell study at Rush University.

Doctors injected 20 million stem cells into Custers neck, and HBO has been following his progress.

Ryans brother, Nick Custer, thanked the West Side community for being so uplifting to his family.

It means the world to us. It just shows you what a special kid Ryan is as a 19-year-old kid going through this, its just overwhelming support, he said.

Nick said Ryan will continue rehabilitation in Cincinnati, and he said Ryan is looking forward to the start of Wright States season.

Ryan wants to get back to the team as soon as possible, and they all want him to come back and help however he can. He misses them, definitely, Nick said.

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Ryan Custer, Elder grad injured at Oxford party, thanks community for their support - WCPO

Spinal Cord Stem Cells Comments Off on Ryan Custer, Elder grad injured at Oxford party, thanks community for their support – WCPO | September 3rd, 2017

GABRIELLA FIORINO

We trust our doctors with our lives. However, what is the reaction when some medical professionals allow unsanitary measures and diseases to break out into the population? Four institutions in the U.S. came under fire recently by the FDA for improperly handling microbiological organisms and exposing the public to smallpox after conducting unapproved techniques, endangering hundreds of lives.

The FDA identified four medical centers in California and Florida as utilizing unapproved stem cell therapies for those with cancer and other serious illnesses. One of the institutes, California Stem Cell Treatment Centers, applied a method developed by StemImmune Inc., which consisted of injecting clients with a mixture of the smallpox vaccine and stem cells. Dr. Mark Berman, co-founder of the California center, described their methods as cutting edge therapy for stage-4 cancer patients, as reported by the Los Angeles Times.

The consequences of such methods are worrisome; as the FDA claims exposure to the smallpox vaccine significantly increases the risk of life-threatening complications, including heart inflammation. Perhaps even more troubling is the fact that individuals in contact with those receiving the vaccine may develop similar symptoms, possibly infecting hundreds of others. The FDA is currently investigating how StemImmune Inc. received shipments of the vaccine, as the product is unavailable on the market.

The Stem Cell Clinic of Sunrise, Florida is another facility under investigation by the FDA for taking improper sanitary measures to prevent contamination during their therapies. According to the agency, the clinic refused to permit entry of an FDA inspector without an appointment, which is a violation of federal law. This refusal would not be the first time the Florida institution came under fire. According to the New England Journal of Medicine, three clients suffering from macular degeneration sustained blindness following treatment at the facility.

A variety of sources derive stem cells, including bone marrow, blood, umbilical cords, and controversially, human embryos. These products aid in the development and restoration of healthy human tissue, and help battle cancer, heart disease, and Parkinsons disease, as noted by the University of Utah. These products are also employed for spinal cord injuries, indicating critical applications, as the central nervous system does not naturally permit neuro-regeneration following damage. Excitingly, organs growth for those requiring life-saving transplants is another possible advancement.

These innovations are not without consequences, however. According to the Mayo Clinic, some may develop graft-versus-host disease, a condition in which a donors stem cells attack the patients tissues and organs, possibly leading to death. Risks of brain tumor development are also an increased possibility for those receiving injections in the spinal cord, as abnormal tissue growth may result.

As the FDA investigates unsound practices by the four institutes endangering the lives of hundreds, Americans should not be misled regarding stem cell therapies. Through proper sanitary measures, their uses are a huge medical development, comprising a myriad of medical advantages. Liberty Nation will keep readers up to date regarding the actions of the FDA against the four clinics.

Gabi is a Biomedical Sciences major and manages a Cognitive Neuroscience Research Lab at the University of Central Florida. A Libertarian, Gabi says shes surrounded on by whiny, wannabe anti-capitalists, posting about their victimhood on Facebook.Although leftists often confuse her with privileged white girls, Gabi is Puerto Rican and Italian.Make sense of that, liberals!

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Stem Cells and "Mishandling" Smallpox - Liberty Nation - Liberty Nation (registration) (blog)

Spinal Cord Stem Cells Comments Off on Stem Cells and "Mishandling" Smallpox – Liberty Nation – Liberty Nation (registration) (blog) | September 3rd, 2017

Bishnupriya Nayak at BMT unit after bone marrow transplantation | Express

BHUBANESWAR: The Haematology Department of SCB Medical College and Hospital (SCBMCH) at Cuttack has notched up a record of sorts and achieved a new milestone in the country by performing 50 bone marrow transplantations in just over three years.

The special Bone Marrow Transplant (BMT) unit started in February 2014 has conducted its 50th procedure on Bishnupriya Nayak (40), a cancer patient from Koelnagar in Rourkela, on Sunday.Head of the department Prof Rabindra Kumar Jena said it is a significant achievement as SCBMCH having all state-of-the-art facilities is the only State-run hospital in the country to complete 50 cases and provide BMT services completely free of cost.

We have a great record of survival rate of patients than other such units elsewhere in the country. Of 50 cases conducted so far, 47 patients are healthy and doing normal activities. Two died due to infection within a month after BMT procedure, another succumbed to brain stroke (not related to BMT or disease) on 178th day, he said.

The BMT unit at SCBMCH has also established a few international and national distinctions. The eldest transplant conducted so far in Asia and Europe region belonged to the unit. Zabar Khan (74), who was suffering from multiple myeloma (a type of blood cancer) is doing fine after the procedure was performed.Similarly, five patients, aged over 65, have been transplanted successfully which is first-of-its-kind in India, Asia and Europe. The first BMT, also known as stem cell transplant, was performed on Sakuntala Sahoo (54) from Kendrapara district on April 23, 2014.

The unit has also mobilised the stem cell adequately in many complicated blood cancer patients who had very low stem cell blood level of 8.7 per micro litre, besides multiple chemotherapy treated cases and successfully performed BMT procedures.

Stating that the priority is being given on adequate stem cell mobilization, collection and engraftment (proper functioning of new bone marrow graft), Prof Jena said the unit is going to start allogenic BMT soon.

We have been doing autologous transplants so far. Our next plan is to start allogenic transplants. We are poised to take complicated cancer patients for BMT. Besides, plans are afoot to expand the unit to a 20-room ward to accommodate huge waiting lists patients, including thalassemia, sickle sell disease and various cancer patients, he added.

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Bone marrow transplant on record run in SCB Medical College and Hospital at Cuttack - The New Indian Express

Bone Marrow Stem Cells Comments Off on Bone marrow transplant on record run in SCB Medical College and Hospital at Cuttack – The New Indian Express | September 3rd, 2017

A recent study has identified a key protein capable of regulating the process of new blood cells, including immune cells, which can potentially improve bone and stem cell transplants for donors as well as recipients. The researchers at Technical University of Dresden, Germany, led by the University of Pennsylvania, USA, found that a protein known as Del-1 occupies a key role in the process of hematopoiesis. In addition, researchers inferred that the protein regulator may be modulated to act as potential drug targets in patients affected by certain blood cancers types.

The findings were reported this week (August 28 September 1, 2017) in The Journal of Clinical Investigation.

Del-1 Expression in Hematopoetic Malignancy Key to Boost Myelopoesis in Bone Marrow Transplants

Initially, some of the researchers discovered that Del-1 was the soluble protein that acted as a powerful drug target in gum diseases. Further investigating the role of the protein in hematopoetic malignancy, they inferred that it played a more global role by establishing its expression in a variety of cell types in bone marrow, most notable of them being endothelial cells, CAR cells, and osteoblasts.

The scientists observed that hematopoietic stem cells plays an increasingly important role in various stressful conditions such as bone marrow injury, stem cell transplantation, or systemic infection. These cells affect the production of myeloid cells that forms the core of bone marrow transplants.

Modulating Protein Regulator may Prove Promising in Some Chemotherapies

The team found that the presence of Del-1 in recipient bone marrow facilitated the process of engrafting in recipients by greatly influencing myelopoesis and consequently boosting the formation of new blood cells. The results were observed in experiments conducted in mice suffering with systemic infection. Whereas, in donors, limiting the interaction between the protein and hematopoetic stem cells could boost donor cell numbers in the blood stream, inferred scientists.

Furthermore, the research team observed that the protein regulator also boosts the production of immune-related blood cells. Thus, this may prove to benefit patients suffering with febrile neutropenia who are undergoing chemotherapy.

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Regulating Bone Marrow Protein can Improve Stem Cell Transplants - CMFE News (press release) (blog)

Bone Marrow Stem Cells Comments Off on Regulating Bone Marrow Protein can Improve Stem Cell Transplants – CMFE News (press release) (blog) | September 3rd, 2017

In BriefResearchers have discovered that acute myeloid leukemia causes leaking from the bone marrow that interferes with chemotherapy delivery. If chemotherapy for AML can be used together with drugs to treat this problem, outcomes may improve dramatically.

Researchers have discovered that the most common form of acute leukemia which strikes adults, acute myeloid leukemia (AML), prevents chemotherapy from being delivered properly by causing bone marrow to leak blood. This means that, by using drugs developed to treat blood vessel and heart problems in concert with chemotherapy, AML might be much more treatable. In this study, these drugs reversed bone marrow leaks in tissue from mice and humans, and also boosted chemotherapy effects. Since these drugs are already in clinical trials for other applications, the team hopes that they may be approved for use in the treatment of AML patients soon.

We found that the cancer was damaging the walls of blood vessels responsible for delivering oxygen, nutrients, and chemotherapy. When we used drugs to stop the leaks in mice, we were able to kill the cancer using conventional chemotherapy, Diana Passaro, Francis Crick Institute researcher and first author of the paper,said in a press release.

The team studied the ways in which AML affects bone marrow by injecting healthy mice with bone marrow from AML patients to create AML mice. They then used intravital microscopy to compare the bone marrow of AML mice with healthy mice and observed pre-loaded fluorescent dyes leaking from the bone marrow blood vessels into the AML mice. Next, they discovered that the cells lining the blood vessels in AML mice were oxygen-starved, which led to increases in nitric oxide (NO), a muscle relaxant. They realized this was probably causing the leaking, and provided NO blockers to the AML mice which slowed leukemia progress and extended remission.

The team not only helped chemotherapy drugs to reach their targets more effectively, but they also found that NO blockers increased stem cells in the bone marrow. This might help healthy cells out-compete cancerous cells, and improve treatment outcomes. Finally, the researchers found that an inability to reduce NO levels and chemotherapy failure were related.

With an average lifetime risk of less than half of one percent among the general population, AML is relatively rare. This is in addition to the fact that AML is a disease that primarily affects older people; the average age of AML patients in the US is 67, and the disease is even rarer before the age of 45. Despite this rarity, however, TheAmerican Cancer Society estimates that there will be around 21,380 new cases of AML in the US in 2017, and about 10,590 deaths, almost all in adults.

This high death rate is linked to the character of this form of cancer, which is particularly aggressive. This is in large part due to chemotherapy resistance and relapse, fewer than 25 percent of patients survive longer than five years after diagnosis. However, if this research leads to a new regimen of combined drug therapy, these numbers may change.

The team is optimistic about their findings and hopes to start clinical trials soon. Weve uncovered a biological marker for this type of leukemia as well as a possible drug target, Francis Crick Institute Group Leader and paper senior author Dominique Bonnet said in the press release. The next step will be clinical trials to see if NO blockers can help AML patients as much as our pre-clinical experiments suggest.

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Chemo-Boosting Drug Discovered for Leukemia - Futurism

Bone Marrow Stem Cells Comments Off on Chemo-Boosting Drug Discovered for Leukemia – Futurism | September 3rd, 2017

This weeks roundup of recent developments in neuroscience kicks off with a study from MIT, where engineers have devised a way to automate the process of monitoring neurons in a living brain using a computer algorithm that analyzes microscope images and guides a robotic arm to the target cell. In the above image, a pipette guided by a robotic arm approaches a neuron identified with a fluorescent stain.

Neurosurgeons at the Center for iPS Cell Research and Application, Kyoto University. They report two new ways to improve outcomes of induced pluropontent stem cell-based therapies for Parkinsons disease in monkey brains. The findings are a key step for patient recruitment of the first iPS cell-based therapy to treat neurodegenerative diseases, since one of the last steps before treating patients with an experimental cell therapy for the brain is confirmation that the therapy works in monkeys.

In other Parkinsons news, the FDA has denied Acorda Therapeutics New Drug Application filing for Inbrija. Inbrija is an inhaled, self-administered, form of levodopa for treating Parkinsons disease. According to the FDA, reason for the denial were the date when the manufacturing site would be ready for inspection, and a question regarding submission of the drug master production record. FDA also requested additional information at resubmission, which was not part of the basis for the refusal.

At the University of Turku, in Finland, researchers have revealed how eating stimulates the brains endogenous opioid system to signal pleasure and satiety. Interestingly, eating both bland and delicious meals triggered significant opioid release in the brain.

A young New York woman with severe headaches represented a never-before-seen case for neurosurgeons at New York Presbyterian. She was diagnosed with an unusual form of hydrocephalus/Chiari malformation, in which the skull is too small and restricted the brain. More about her in the video below:

Tinnitus, a chronic ringing or buzzing in the ears, has eluded medical treatment and scientific understanding. A new University of Illinois at Urbana-Champaign study found that chronic tinnitus is associated with changes in certain networks in the brain, and furthermore, those changes cause the brain to stay more at attention and less at rest. The finding provides patients with validation of their experiences and hope for future treatment options.

In social media news, research by BuzzFeed found more than half of the most-shared scientific stories about autism published in the last five years promote unevidenced or disproven treatments, or purported causes. More disturbingly, families in the autism community are excessively targeted by purveyors of bad information, making them more vulnerable to harmful, unproven so-called treatments.

Top Image: Ho-Jun Suk

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This Week In Neuroscience News 8/31/17 - ReliaWire

IPS Cell Therapy Comments Off on This Week In Neuroscience News 8/31/17 – ReliaWire | September 3rd, 2017

01 Sep 2017

A paper in the September 1 Nature claims a cadre of rogue microglia are all it takes to orchestrate neurodegeneration. Researchers led by Frederic Geissmann and Omar Abdel-Wahab of Memorial Sloan Kettering Cancer Center in New York, and Marco Prinz of the University of Freiburg in Germany, induced a somatic mutation in about 10 percent of microglia that switched on ERK kinase signaling. The mice later developed a severe neurodegenerative disease that paralyzed them. The researchers determined that damaging inflammation caused by the mutated microglia was likely to blame. The findings raise the possibility that similar somatic mutations in people are responsible for a rare neurodegenerative disease that occurs inchildren.

This is a great paper for many reasons, commented Bart De Strooper of the Dementia Research Institute in the U.K. I am particularly excited about the concept of acquired genetic mosaicism as a cause of neurodegenerative disorder. The paper also shows that microglia mutations can be directly causative inneurodegeneration.

Most famous for their role in causing cancer, somatic mutations can spontaneously arise in any cell, sometimes giving it a proliferative edge. Mutations in the RAS-MEK-ERK signaling pathway, for example, can cause diseases called histiocytoses if they arise in the myeloid cell lineage, which gives rise to blood and immune cells, including macrophages and microglia. Histiocytoses manifest in different ways, including leukemias, other tumors, and malfunctions in multiple organs. Mysteriously, a small fraction of carriers also get a neurodegenerative disease that manifests between childhood and middle age, with symptoms such as cerebellar ataxia and tremor (Lachenal et al., 2006; Wnorowski et al., 2008). The reason for the neurodegeneration has been amystery.

Geissmann and colleagues speculated it could be caused by microglia descended from erythro-myeloid progenitor cells (EMPs) harboring the same RAS-MEK-ERK somatic mutations. EMPs arise in the embryonic yolk sac early in development, and give rise to microglia in the brain and macrophages in other tissues (Perdiguero et al., 2014; Feb 2015 conference news).In contrast, circulating monocytes are continually replenished by hemotopoietic stem cells (HSCs) in the bonemarrow.

Doomed During Development? Histiocytoses arise from somatic mutations in hematopoietic stem cells (HSCs, left) or in erythro-myeloid progenitor (EMP) cells (right), which give rise to macrophages and microglia. The mutant microglia may cause inflammation, leading to neurodegeneration. [Courtesy of Tarnawsky and Yoder, Nature, News & Views,2017.]

To find out if somatic mutations in EMPs could beget microglia that trigger neurodegeneration, first author Elvira Mass and colleagues induced a somatic mutation that causes histiocytoses into mice. They chose the V600E variant of the BRAF gene, a substitution that switches on ERK signaling. The researchers generated transgenic mice carrying an inducible copy of the mutated BRAF gene, which could only be switched on via tamoxifen-induced Cre recombination in EMPs. This also turned on yellow fluorescent protein so the researchers could identify the cells. At embryonic day 8.5, they injected pregnant mice with a teeny dose of the drug to ensure that only a fraction of the embryos EMPs would express the mutation. About 10 percent of tissue resident macrophages, including microglia, in the resulting offspring expressed V600E BRAF at one month ofage.

The mutant microglia took up their positions in the brain, but were different from their normal counterparts from the get-go. Those carrying the V600E BRAF expressed elevated markers of proliferation, ERK signaling, and inflammation. In one-month-old mice, these feisty microglia had yet to cause trouble, but by four months of age, the researchers noticed neurological symptoms in the mice, including loss of hind limb reflexes and shortened stride. At seven months, 90 percent of the animals were affected and by nine months 60 percent of the mice had full hind limb paralysis. These symptoms, similar to cerebellar ataxia, are common in people with cerebral histiocytoses. Feeding the mice a BRAF inhibitor starting at one month of age drastically delayed onset and slowedprogression.

Compared to wild-type mice (left), animals with induced BRAF mutations in their EMPs had an expansion of mutant microglia expressing YFP in their spinal cord (middle). Microglia also expressed the activation marker CD68 (top) and phosphorylated ERK (bottom). [Courtesy of Mass et al., Nature2017.]

The researchers next searched for pathological changes that could have triggered the disorder. In month-old mice, the researchers found signs of elevated microglial and astrocyte activation, but not neuronal death. Oddly, by immunohistochemistry using the 22C11 antibody, the researchers noticed deposits of amyloid precursor protein (APP) in the inflamed areas, a phenomenon that Geissmann attributed to release of the membrane protein from newly damaged axons. In six-month-old animals, large clusters of activated, phagocytic microglia carrying the BRAF mutation crowded in the thalamus, brain stem, cerebellum, and spinal cord. These same regions were rife with synaptic and neuronal loss, demyelination, and astrogliosis. The mutant microglia had a small proliferative advantage compared with their wild-type counterparts, but Geissmann attributed the bulk of the neuronal damage to the activation of the cells, rather than their expansion. Treatment with a BRAF inhibitor mitigated theseresponses.

Gene expression analysis of mutant microglia taken from paralyzed mice revealed the differential expression of around 8,000 genes, 80 percent of which were upregulated compared to microglia from control mice. These genes included a bevy of pro-inflammatory mediators, including cytokines, phagocytosis boosters, matrix proteins, and growthfactors.

For some reason, the thalamus, brain stem, cerebellum, and spinal cord were uniquely vulnerable to the presence of the V600E BRAF mutant cells. Tissue macrophages carrying the mutation also expanded in the liver, spleen, kidney, and lung, even more so than in the brain, but did not cause damage in those regions. Geissmann speculated that differences in the tissue microenvironment could play a role in this selective vulnerability. For example, normal liver macrophages are in a near constant state of activation, Geissmann said, so the organ is equipped to deal with them. Perhaps the posterior part of the brain is unaccustomed to constant microglial activation, he said. Indeed, chronic microglial activation occurs during AD as well, and appears to ultimately inflict damage, rather than helpfulresponses.

Finally, the researchers investigated whether patients with histiocytoses also had abnormal microglia. They analyzed postmortem brain tissue from three patients with Erdheim-Chester disease (ECD), and conducted gene expression analysis on brain biopsies from one person with Langerhans cell histiocytosis (LCH), and another with juvenile xanthogranuloma (JXG). All of these patients had neurodegenerative disease associated with their histiocytoses, which were all caused by BRAF V600E mutations. In the ECD samples, the researchers spotted abundant activated microglia gathered at sites of neuronal loss, astrogliosis, and demyelination. Compared with data from five control samples, gene expression analysis on the JXG and LCH samples revealed an upregulation of genes in the MAPK pathway, including multiple pro-inflammatorycytokines.

The findings support the idea that activated microglia wreak havoc in the brain and cause neurodegeneration in people withhistiocytoses.

For a somatic mutation to have an effect, affected cells must propagate sufficiently. EMPs proliferate during early development, making it a prime time for mutant clones to multiply, Geissmann said. Perhaps the number of mutant clones born during the EMP stage would suffice to harm neurons, he said. However, if microglia are also bestowed with a proliferative edge, this would likely exacerbate the damage, he added. Either way, Geissmann proposed that inhibitors of ERK signaling might thwart neurodegeneration when mutant microglia areinvolved.

In an accompanying editorial, Stefan Tarnawsky and Mervin Yoder at Indiana University in Indianapolis noted opportunities for better diagnosis in this scenario. When somatic mutations occur in EMPs during early development, macrophages in many regions of the body will likely carry the mutations, not just microglia in the brain. This suggests that it might be possible to collect macrophage samples from more easily accessible, non-CNS tissues to look for biomarkers when diagnosing microglia-related disease, theywrote.

What about somatic mutations that might arise later in life, when tissue resident macrophages or microglia are already nestled into their permanent residences? Though recent studies reported that microglia are relatively long-lived cells, they proliferate in response to threats (Aug 2017 news),perhaps setting the stage for expansion of mutant cells, Geissmann speculated. That said, beyond people with histiocytoses, the contribution of somatic mutations in microglia to neurodegenerative disease is unclear. De Strooper and others have reported that genetic mosaicism in neurons could cause neurodegeneration (Jul 2015 news). A major impediment to studying this phenomenon is that somatic mutations that arise in the brain go undetected in standard genomic sequencing.JessicaShugart

No Available Further Reading

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Somatic SNAFUCan a Few Mutant Microglia Cause Neurodegenerative Disease? - Alzforum

Spinal Cord Stem Cells Comments Off on Somatic SNAFUCan a Few Mutant Microglia Cause Neurodegenerative Disease? – Alzforum | September 3rd, 2017

Monkeys with Parkinsons disease symptoms show significant improvement over two years after being transplanted neurons prepared from human induced pluropontent stem cells, scientists at the Center for iPS Cell Research and Application (CiRA), Kyoto University, report. One of the last steps before treating patients with an experimental cell therapy for the brain is confirmation that the therapy works in monkeys.

Parkinsons disease degenerates a specific type of cells in the brain known as dopaminergic (DA) neurons. It has been reported that when symptoms are first detected, a patient will have already lost more than half of his or her DA neurons.

Several studies have shown the transplantation of DA neurons made from fetal cells can mitigate the disease.

The use of fetal tissues is controversial, however. On the other hand, iPS cells can be made from blood or skin.

Our research has shown that DA neurons made from iPS cells are just as good as DA neurons made from fetal midbrain. Because iPS cells are easy to obtain, we can standardize them to only use the best iPS cells for therapy,

said Professor Jun Takahashi, a neurosurgeon specializing in Parkinsons disease, who plans to use DA neurons made from iPS cells to treat patients.

To test the safety and effectiveness of DA neurons made from human iPS cells, Tetsuhiro Kikuchi, a neurosurgeon working in the Takahashi lab, transplanted the cells into the brains of monkeys.

We made DA neurons from different iPS cells lines. Some were made with iPS cells from healthy donors. Others were made from Parkinsons disease patients,

said Kikuchi, who added that the differentiation method used to convert iPS cells into neurons is suitable for clinical trials.

It is generally assumed that the outcome of a cell therapy will depend on the number of transplanted cells that survive, but Kikuchi found this was not the case. More important than the number of cells was the quality of the cells.

Each animal received cells prepared from a different iPS cell donor. We found the quality of donor cells had a large effect on the DA neuron survival, Kikuchi said.

To understand why, he looked for genes that showed different expression levels, finding 11 genes that could mark the quality of the progenitors. One of those genes was Dlk1.

Dlk1 is one of the predictive markers of cell quality for DA neurons made from embryonic stem cells and transplanted into rat. We found Dlk1 in DA neurons transplanted into monkey. We are investigating Dlk1 to evaluate the quality of the cells for clinical applications.

Another feature of the study that is expected to extend to clinical study is the method used to evaluate cell survival in the host brains. The study demonstrated that magnetic resonance imaging (MRI) and position electron tomography (PET) are options for evaluating the patient post surgery.

MRI and PET are non-invasive imaging modalities. Following cell transplantation, we must regularly observe the patient. A non-invasive method is preferred,

said Takahashi.

The group is hopeful that it can begin recruiting patients for this iPS cell-based therapy before the end of next year. The study is the teams answer to bring iPS cells to clinical settings, said Takahashi.

Tetsuhiro Kikuchi, Asuka Morizane, Daisuke Doi, Hiroaki Magotani, Hirotaka Onoe, Takuya Hayashi, Hiroshi Mizuma, Sayuki Takara, Ryosuke Takahashi, Haruhisa Inoue, Satoshi Morita, Michio Yamamoto, Keisuke Okita, Masato Nakagawa, Malin Parmar, Jun TakahashiHuman iPS cell-derived dopaminergic neurons function in a primate Parkinsons disease modelNature, 2017; 548 (7669): 592 DOI: 10.1038/nature23664

Image: Annie Cavanagh / Wellcome Images

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iPS Cell-based Neuron Therapy Benefits Monkeys With Parkinson's - ReliaWire

Skin Stem Cells Comments Off on iPS Cell-based Neuron Therapy Benefits Monkeys With Parkinson’s – ReliaWire | September 3rd, 2017

Wed,17 Dec 2003 05:30:00

Bone marrow transplant is a procedure in which healthy bone marrow is transplanted into a patient whose bone marrow is not functioning properly. Problems in bone marrow are often caused by chemotherapy or radiation treatment for cancer. This procedure can also be done to correct hereditary blood diseases. The healthy bone marrow may be taken from the patient prior to chemotherapy or radiation treatment (autograft), or it may be taken from a donor (allograft).

Wed,17 Dec 2003 05:30:00

Bone marrow is the soft, sponge-like material found inside bones. It contains immature cells called stem cells that produce blood cells. There are three types of blood cells: white blood cells, which fight infection; red blood cells, which carry oxygen to and from organs and tissues; and platelets, which enable the blood to clot.

Wed,17 Dec 2003 05:30:00

Alternatively, hereditary or acquired disorders may cause abnormal blood cell production. In these cases, transplantation of healthy bone marrow may save a patient's life. Transplanted bone marrow will restore production of white blood cells, red blood cells, and platelets.

Wed,17 Dec 2003 05:30:00

Donated bone marrow must match the patient's tissue type. It can be taken from the patient, a living relative (usually a brother or a sister), or from an unrelated donor. Donors are matched through special blood tests called HLA tissue typing.

Bone marrow is taken from the donor in the operating room while one is unconscious and pain-free (under general anaesthesia). Some of the donor's bone marrow is removed from the top of the hip bone. The bone marrow is filtered, treated, and transplanted immediately or frozen and stored for later use. Then, transplant material is transfused into the patient through a vein and is naturally transported back into the bone cavities where it grows to replace the old bone marrow.

Alternatively, blood cell precursors, called stem cells, can be induced to move from the bone marrow to the blood stream using special medications. These stem cells can then be taken from the bloodstream through a procedure called leukapheresis.

The patient is prepared for transplantation by administering high doses of chemotherapy or radiation (conditioning). This serves two purposes. First, it destroys the patient's abnormal blood cells or cancer. Second, it inhibits the patient's immune response against the donor bone marrow (graft rejection).

Following conditioning, the patient is ready for bone marrow infusion. After infusion, it takes 10 to 20 days for the bone marrow to establish itself. During this time, the patient requires support with blood cell transfusions.

Wed,17 Dec 2003 05:30:00

Wed,17 Dec 2003 05:30:00

The major problem with bone marrow transplants (when the marrow comes from a donor, not the patient) is graft-versus-host disease. The transplanted healthy bone marrow cells may attack the patient's cells as though they were foreign organisms. In this case, drugs to suppress the immune system must be taken, but this also decreases the body's ability to fight infections.

Other significant problems with a bone marrow transplant are those of all major organ transplants - finding a donor and the cost. The donor is usually a sibling with compatible tissue. The more siblings the patient has, the more chances there are of finding a compatible donor.

Wed,17 Dec 2003 05:30:00

The patient will require attentive follow-up care for 2 to 3 months after discharge from the hospital. It may take 6 months to a year for the immune system to fully recover from this procedure.

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Bone marrow transplant - Doctor NDTV

Bone Marrow Stem Cells Comments Off on Bone marrow transplant – Doctor NDTV | September 1st, 2017

Scientific pioneer, superstar surgeon, miracle worker thats how Paolo Macchiarini was known for several years. Dressed in a white lab coat or in surgical scrubs, with his broad, handsome face and easy charm, he certainly looked the part. And fooled almost everyone.

Macchiarini shot to prominence back in 2008, when he created a new airway for Claudia Castillo, a young woman from Barcelona. He did this by chemically stripping away the cells of a windpipe taken from a deceased donor; he then seeded the bare scaffold with stem cells taken from Castillos own bone marrow. Castillo was soon back home, chasing after her kids. According to Macchiarini and his colleagues, her artificial organ was well on the way to looking and functioning liked a natural one. And because it was built from Castillos own cells, she didnt need to be on any risky immunosuppressant drugs.

This was Macchiarinis first big success. Countless news stories declared it a medical breakthrough. A life-saver and a game-changer. We now know that wasnt true. However, the serious complications that Castillo suffered were, for a long time, kept very quiet.

Meanwhile, Macchiarinis career soared. By 2011, he was working in Sweden at one of the worlds most prestigious medical universities, the Karolinska Institute, whose professors annually select the winner of the Nobel prize in physiology or medicine. There he reinvented his technique. Instead of stripping the cells from donor windpipes, Macchiarini had plastic scaffolds made to order. The first person to receive one of these was Andemariam Beyene, an Eritrean doctoral student in geology at the University of Iceland. His recovery put Macchiarini on the front page of the New York Times.

Macchiarini was turning the dream of regenerative medicine into a reality. This is how NBCs Meredith Vieira put it in her documentary about Macchiarini, appropriately called A Leap of Faith: Just imagine a world where any injured or diseased organ or body part you have is simply replaced by a new artificial one, literally manmade in the lab, just for you. This marvelous world was now within reach, thanks to Macchiarini.

Last year, however, the dream soured, exposing an ugly reality.

Macchiarini gave his regenerating windpipes to 17 or more patients worldwide. Most, including Andemariam Beyene, are now dead. Those few patients who are still alive including Castillo have survived in spite of the artificial windpipes they received.

In January 2016, Macchiarini received an extraordinary double dose of bad press. The first was a Vanity Fair article about his affair with Benita Alexander, an award-winning producer for NBC News. She met Macchiarini while producing A Leap of Faith and was soon breaking one of the cardinal rules of journalism: dont fall in love with the subject of your story.

By the time the program aired, in mid-2014, the couple were planning their marriage. It would be a star-studded event. Macchiarini had often boasted to Alexander of his famous friends. Now they were on the wedding guest list: the Obamas, the Clintons, Vladimir Putin, Nicolas Sarkozy and other world leaders. Andrea Bocelli was to sing at the ceremony. None other than Pope Francis would officiate, and his papal palace in Castel Gandolfo would serve as the venue. Thats what Macchiarini told his fiancee.

But as the big day approached, Alexander saw these plans unravel, and finally realised that her lover had lied about almost everything. The pope, the palace, the world leaders, the famous tenor they were all fantasies.

Likewise the whole idea of a wedding: Macchiarini was still married to his wife of 30 years.

Macchiarinis deceit was so outlandish, Vanity Fair sought the opinion of the Harvard professor Ronald Schouten, an expert on psychopaths, who gave this diagnosis-at-a-distance: Macchiarini is the extreme form of a con man. Hes clearly bright and has accomplishments, but he cant contain himself. Theres a void in his personality that he seems to want to fill by conning more and more people.

Which left a big, burning question in the air: if Macchiarini was a pathological liar in matters of love, what about his medical research? Was he conning his patients, his colleagues and the scientific community?

The answer came only a couple of weeks later, when Swedish television began broadcasting a three-part expos of Macchiarini and his work.

Called Experimenten (The Experiments), it argued convincingly that Macchiarinis artificial windpipes were not the life-saving wonders wed all been led to believe. On the contrary, they seemed to do more harm than good something that Macchiarini had for years concealed or downplayed in his scientific articles, press releases and interviews.

Faced with this public relations disaster, the Karolinska Institute immediately promised to investigate the allegations but then, within days, suddenly announced that Macchiarinis contract would not be extended.

Macchiarinis fall was swift, but troubling questions remain about why he was allowed to continue his experiments for so long. Some answers have emerged from the official inquiries into the Karolinska Institute and the Karolinska University hospital. They identified many problems with the way the twin organisations handled him.

Macchiarinis fame had won him well-placed backers. These included Harriet Wallberg, who was the vice-chancellor of the Karolinska Institute in 2010, when Macchiarini was recruited. She pushed through his appointment despite the fact that he had some very negative references and dubious claims on his rsum.

This set a dangerous example. It showed department heads and colleagues that they should give Macchiarini special treatment.

He could do pretty much as he pleased. In the first couple of years at Karolinska, he put plastic airways into three patients. Since this was radically new, Macchiarini and his colleagues should have tested it on animals first. They didnt.

Likewise, they didnt undertake a proper risk assessment of the procedure, nor did Macchiarinis team seek government permits for the plastic windpipes, stem cells, and chemical growth factors they used. They didnt even seek the approval of Stockholms ethical review board, which is based at Karolinska.

Though Macchiarini was in the public eye, he was able to sidestep the usual rules and regulations. Or rather, his celebrity status helped him do so. Karolinskas leadership expected big things from their superstar, things that would bring prestige and funding to the institute.

They also cited a loophole known as compassionate use. Macchiarini, they claimed, wasnt really doing clinical research. No, he was just caring for his patients who were, one and all, facing certain death with no other treatment options available and no time to waste. In such dire circumstances, new treatments can be tried as a last resort.

This argument didnt wash with those who later investigated the case. In their view, Macchiarini was certainly engaged in clinical research. Besides which, compassionate concerns dont override the basic principles of patient safety and informed consent. Macchiarini, meanwhile, said he did not accept the findings of the disciplinary board.

As it turned out, Macchiarinis patients werent all at deaths door at the time he treated them. Andemariam Beyene, for instance, had recurrent cancer of the windpipe but, aside from a cough, was still in good health. But even if his days had been numbered, this didnt necessarily justify what Macchiarini put him through.

Beyenes death two and a half years after the operation, caused by the failure of his artificial airway, was a grueling ordeal. According to Pierre Delaere, a professor of respiratory surgery at KU Leuven, Belgium, Macchiarinis experiments were bound to end badly. As he said in Experimenten: If I had the option of a synthetic trachea or a firing squad, Id choose the last option because it would be the least painful form of execution.

Delaere was one of the earliest and harshest critics of Macchiarinis engineered airways. Reports of their success always seemed like hot air to him. He could see no real evidence that the windpipe scaffolds were becoming living, functioning airways in which case, they were destined to fail. The only question was how long it would take weeks, months or a few years.

Delaeres damning criticisms appeared in major medical journals, including the Lancet, but werent taken seriously by Karolinskas leadership. Nor did they impress the institutes ethics council when Delaere lodged a formal complaint.

Support for Macchiarini remained strong, even as his patients began to die. In part, this is because the field of windpipe repair is a niche area. Few people at Karolinska, especially among those in power, knew enough about it to appreciate Delaeres claims. Also, in such a highly competitive environment, people are keen to show allegiance to their superiors and wary of criticising them. The official report into the matter dubbed this the bandwagon effect.

With Macchiarinis exploits endorsed by management and breathlessly reported in the media, it was all too easy to jump on that bandwagon.

And difficult to jump off. In early 2014, four Karolinska doctors defied the reigning culture of silence by complaining about Macchiarini. In their view, he was grossly misrepresenting his results and the health of his patients. An independent investigator agreed. But the vice-chancellor of Karolinska Institute, Anders Hamsten, wasnt bound by this judgement. He officially cleared Macchiarini of scientific misconduct, allowing merely that hed sometimes acted without due care.

For their efforts, the whistleblowers were punished. When Macchiarini accused one of them, Karl-Henrik Grinnemo, of stealing his work in a grant application, Hamsten found him guilty. As Grinnemo recalls, it nearly destroyed his career: I didnt receive any new grants. No one wanted to collaborate with me. We were doing good research, but it didnt matter I thought I was going to lose my lab, my staff everything.

This went on for three years until, just recently, Grinnemo was cleared of all wrongdoing.

The Macchiarini scandal claimed many of his powerful friends. The vice-chancellor, Anders Hamsten, resigned. So did Karolinskas dean of research. Likewise the secretary-general of the Nobel Committee. The university board was dismissed and even Harriet Wallberg, whod moved on to become the chancellor for all Swedish universities, lost her job.

Unfortunately, the scandal is much bigger than Karolinska, which accounts for only three of the patients who have received Macchiarinis regenerating windpipes.

The other patients were treated at hospitals in Barcelona, Florence, London, Moscow, Krasnodar, Chicago and Peoria. None of these institutions have faced the same kind of public scrutiny. None have been forced to hold full and independent inquiries. They should be.

If the sins of Karolinska have been committed elsewhere, it is partly because medical research facilities share a common milieu, which harbours common dangers. One of these is the hype surrounding stem cells.

Stem cell research is a hot field of science and, according to statistics, also a rather scandal-prone one. Articles in this area are retracted 2.4 times more often than the average for biomedicine, and over half of these retractions are due to fraud.

Does the heat of stem cell research the high levels of funding, prestige and media coverage it enjoys somehow encourage fraud? Thats what our experience of medical research leads us to suspect. While there isnt enough data to actually prove this, we do have some key indicators.

We have, for example, a growing list of scientific celebrities who have committed major stem cell fraud. There is South Koreas Hwang Woo-suk who, in 2004, falsely claimed to have created the first human embryonic stem cells by means of cloning. A few years ago, Japans Haruko Obokata pulled a similar con when she announced to the world a new and simple and fake method of turning ordinary body cells into stem cells.

Hwang, Obokata and Macchiarini were all attracted to the hottest regions of stem cell research, where hope for a medical breakthrough was greatest. In Macchiarinis case, the hope was that patients could be treated with stem cells taken from their own bone marrow.

Over the years, this possibility has generated great excitement and a huge amount of research. Yet, for the vast majority of such treatments, there is little solid evidence that they work. (The big exception is blood stem cell transplantation, which has been saving the lives of people with leukemia and other cancers of the blood for decades.)

Its enough to worry officials from the US Food and Drug Administration (FDA). They recently published an article in the New England Journal of Medicine admitting that stem cell research has mostly failed to live up to its therapeutic promise.

An alarmingly wide gap has grown between what we expect from stem cells and what they deliver. Each new scientific discovery brings a flood of stories about how it will revolutionise medicine one day soon. But that day is always postponed.

An unhappy result of this is the rise of pseudo-scientific therapies. Stem cell clinics have sprung up like weeds, offering to treat just about any ailment you can name. In place of clinical data, there are gushing testimonials. There are also plenty of desperate patients who believe because theyve been told countless times that stem cells are the cure, and who cannot wait any longer for mainstream medicine. They and their loved ones fall victim to false hope.

Scientists can also suffer from false hope. To some extent, they believed Macchiarini because he told them what they wanted to hear. You can see this in the speed with which his breakthroughs were accepted. Only four months after Macchiarini operated on Claudia Castillo, his results provisional but very positive were published online by the Lancet. Thereafter it was all over the news.

The popular press also has a lot to answer for. Its love of human interest stories makes it sympathetic to unproven therapies. As studies have shown, the media often casts a positive light on stem cell tourism, suggesting that the treatments are effective and the risks low. It did much the same for Macchiarinis windpipe replacements. A good example is the NBC documentary A Leap of Faith. Its fascinating to rewatch as a lesson on how not to report on medical science.

It is fitting that Macchiarinis career unravelled at the Karolinska Institute. As the home of the Nobel prize in physiology or medicine, one of its ambitions is to create scientific celebrities. Every year, it gives science a show-business makeover, picking out from the mass of medical researchers those individuals deserving of superstardom. The idea is that scientific progress is driven by the genius of a few.

Its a problematic idea with unfortunate side effects. A genius is a revolutionary by definition, a risk-taker and a law-breaker. Wasnt something of this idea behind the special treatment Karolinska gave Macchiarini? Surely, he got away with so much because he was considered an exception to the rules with more than a whiff of the Nobel about him. At any rate, some of his most powerful friends were themselves Nobel judges until, with his fall from grace, they fell too.

If there is a moral to this tale, its that we need to be wary of medical messiahs with their promises of salvation.

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Dr Con Man: the rise and fall of a celebrity scientist who fooled almost everyone - The Guardian

Bone Marrow Stem Cells Comments Off on Dr Con Man: the rise and fall of a celebrity scientist who fooled almost everyone – The Guardian | September 1st, 2017

Bone marrow contains hematopoetic stem cells, the precursors to every blood cell type. These cells spring into action following bone marrow transplants, bone marrow injury and during systemic infection, creating new blood cells, including immune cells, in a process known as hematopoiesis.

A new study led by University of Pennsylvania and Technical University of Dresden scientists has identified an important regulator of this process, a protein called Del-1. Targeting it, the researchers noted, could be an effective way to improve stem cell transplants for both donors and recipients. There may also be ways to modulate levels of Del-1 in patients with certain blood cancers to enhance immune cell production. The findings are reported this week in The Journal of Clinical Investigation.

Because the hematopoetic stem cell niche is so important for the creation of bone marrow and blood cells and because Del-1 is a soluble protein and is easily manipulated, one can see that it could be a target in many potential applications, said George Hajishengallis, the Thomas W. Evans Centennial Professor in the Department of Microbiology in Penns School of Dental Medicine and a senior author on the work.

I think that Del-1 represents a major regulator of the hematopoetic stem cell niche, said Triantafyllos Chavakis, co-senior author on the study and a professor at the Technical University of Dresden. It will be worthwhile to study its expression in the context of hematopoetic malignancy.

For Hajishengallis, the route to studying Del-1 in the bone marrow began in his field of dental medicine. Working with Chavakis, he had identified Del-1 as a potential drug target for gum disease after finding that it prevents inflammatory cells from moving into the gums.

Both scientists and their labs had discovered that Del-1 was also expressed in the bone marrow and began following up to see what its function was there.

In the beginning, I thought it would have a simple function, like regulating the exit of mature leukocytes [white blood cells]from the marrow into the periphery, Hajishengallis said, something analogous to what it was doing in the gingiva. But it turned out it had a much more important and global role than what I had imagined.

The researchers investigations revealed that Del-1 was expressed by at least three cell types in the bone marrow that support hematopoetic stem cells: endothelial cells, CAR cells and osteoblasts. Using mice deficient in Del-1, they found that the protein promotes proliferation and differentiation of hematopoetic stem cells, sending more of these progenitor cells down a path toward becoming myeloid cells, such as macrophages and neutrophils, rather than lymphocytes, such as T cells and B cells.

In bone marrow transplant experiments, the team discovered that the presence of Del-1 in recipient bone marrow is required for the transplanted stem cells to engraft in the recipient and to facilitate the process of myelopoesis, the production of myeloid cells.

When the researchers mimicked a systemic infection in mice, animals deficient in Del-1 were slower to begin making myeloid cells again compared to those with normal Del-1 levels.

We saw roles for Del-1 in both steady state and emergency conditions, Hajishengallis said.

Hajishengallis, Chavakis and their colleagues identified the protein on hematopoetic stem cells with which Del-1 interacts, the 3 integrin, perhaps pointing to a target for therapeutic interventions down the line.

The scientists see potential applications in bone marrow and stem cell transplants, for both donors and recipients. In donors, blocking the interaction between Del-1 and hematopoetic stem cells could enhance the mobilization of those progenitors into the bloodstream. This could be helpful for increasing donor cell numbers for transplantation. Transplant recipients, on the other hand, may need enhanced Del-1 interaction to ensure the transplanted cells engraft and begin making new blood cells more rapidly.

In addition, people undergoing chemotherapy who develop febrile neutropenia, associated with low levels of white blood cells, might benefit from the role of Del-1 in supporting the production of immune-related blood cells such as neutrophils.

Its easy to think of practical applications for these findings, said Hajishengallis. Now we need to find out whether it works in practice, so our studies continue.

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Targeting bone marrow protein could be effective way to improve ... - Gears Of Biz

Bone Marrow Stem Cells Comments Off on Targeting bone marrow protein could be effective way to improve … – Gears Of Biz | September 1st, 2017

You might feel a bit down if you watch the news. Who wouldnt?

Angry people might be grabbing headlines and making you wonder about the future, but the antidote is all around you.

Talk to some of your neighbours. Chances are, no matter what they look like or where theyre originally from, youll find theyre actually pretty decent people just like you.

The little improvements we all try to make may not register much, but the accumulation of them all eventually does.

And if theres one tangible piece of proof that the world is changing for the better, its Lucas Lindner.

2016 was not a kind year for 22-year-old Lucas.

Last May he lost control of his pickup truck when a deer ran out on the road. The front passenger tire blew out. The truck rolled, throwing him out of the window.

When he woke up in the hospital, he was paralysed from the neck down. He was just heading to the grocery store on a Wisconsin Sunday morning.

It was an accident that could happen to anyone, to a friend or relative.

Normally, people like Lucas have no hope of restoring motor control of their bodies ever again.

In the United States, this awful story plays out 17,000 times every year. There are a quarter of a million people in the country with paralysis.

But Lucas story is working out a little bit differently.

Lucas was airlifted to Froedtert Hospital, a teaching hospital of the Medical College of Wisconsin.

There, Dr. Shekar N. Kurpad, professor of neurosurgery, applied 15 years of research into cell transplantation for spinal cord injury.

The procedure revolutionary and so were the cells Dr. Kurpad used.

The new procedure used cells that were developed over many years by researchers at a two companies leading the way in regenerative medicine.

Researchers at these companies have discovered how to grow stem cells and make them reliable for transplantation use.

On doctor, in fact, who Ive researched extensively, has been called the father of regenerative medicine.

Ive had the pleasure of meeting with him on a number of occasions.

Whenever I am in the San Francisco Bay Area, I try to visit him to learn whats going on in the field.

And from what Ive seen the therapeutic potential is hard to understate.

And were starting to see the results in people like Lucas Lindner.

Hes still wheelchair-bound we have a lot more to learn but he now has fine motor skills in his upper body. Thats extraordinary in cases like his.

Lucass miraculous improvement is due to newly designed pluripotent stem cells They are called pluripotent because they have the power to transform into any other cell type in the body.

And this Bay Area doctors company has accumulated the technology to make that happen.

Over the next few months, well get more clinical data from patients being treated with the full 20 million-cell dose and potentially more great news of restored motor function.

The recent headlines may have been about a few angry people rioting and hating each other, but the real important news is this

Recently, when the Cincinnati Reds played the Milwaukee Brewers, Lucas threw out the opening pitch.

Many U.S. presidents and other famous people have thrown pitches, but no pitch has been as historic as this one. And the advances I highlighted today are the reason why.

As this therapy matures and gets closer to market, I believe it will make a big impact on shares of companies in this space.

Which means the right-timed move in the upcoming months means a huge potential windfall of cash for you.

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A year ago he was paralysed from the neck down then this happened - The Daily Reckoning

Spinal Cord Stem Cells Comments Off on A year ago he was paralysed from the neck down then this happened – The Daily Reckoning | September 1st, 2017

Scientists around the world are researching ways to reverse the aging process. There have been a few scientific breakthroughs in the last years, such as a March 2013, Science report. The report discussed how a team of scientists at the University of New South Wales had successfully reversed the aging process in mice with a NAD+ booster, NMN that stimulated the natural repair processes in cells (1).

In August 2017, a different technique was reported. According to ScienceDaily. its being touted as a possible fountain of youth. The ability to rejuvenate the heart and even reverse aging is the claim of a recent study (2).

The European Heart Journal published the study where researchers injected cardiac stem cells taken from the hearts of newborn lab rats into the hearts of old rats (22 months old, which is considered old for a rat lifespan). The result was a reversal in their aging hearts. The paper claims that the old rats appeared newly invigorated after receiving their injections.

In fact, the researchers noticed a 20% increase in the old rats exercising ability. Certainly, the scientists anticipated that this treatment would improve the old rats hearts, what they didnt expect were other benefits, such as the rat fur (shaved away for the surgery) growing back faster than normal.

In addition, the scientists noticed that the rats telomeres had changed. Instead shrinking, the common effect of aging, the telomers in the treated rats actually lengthened. This was an astounding side-effect of the cardiac stem cell injections.

Telomeres are repetitive nucleotide sequences that are found along the ends of chromosomes and become like protective caps. They prevent the ends of the chromosomes from deteriorating, as well as fusing with other chromosomes. Unfortunately, this protection begins to wear away with age and the length of the telomeres shorten as the body ages (3).To discover that the rats telomeres grew longer along with other systemic rejuvenating effects, the primary investigator on the research and director of the Cedars-Sinai Heart Institute Dr Eduardo Marbn proclaimed that it was like discovering, an unexpected fountain of youth.

Dr Marbns team completed the worlds first cardiac stem cell infusion in 2009. Dr Marbn developed the process of growing cardiac-derived stem cells when he was at John Hopkins University. Hes continued his research at Cedars-Sinai.

Conducting research in various heart-related cell therapy for more than 12 years, some of that research included using cardiosphere-derived cells.

According to Life Map Discovery, Cardiosphere-derived cells are isolated from atrial or ventricular biopsy specimens of patients undergoing heart surgery. The tissues are processed and cultured until a fibroblast-like cell layer forms. In this process, some cells migrate to this layer and techs can use them to further isolate and culture to create cardiospheres (4).

A March 2012 publication by the Journal of the American College of Cardiology (JACC) discussed the injection of cardiosphere-derived cells (CDCs) into infarcted mouse hearts. The injections resulted in superior improvement of cardiac function. (5)

According to Dr Marbn, Our previous lab studies and human clinical trials have shown promise in treating heart failure using cardiac stem cell infusions.

In the teams latest study, they used a specific type of stem cells taken from the newborn rats. Instead of stem cells, anther group received a placebo treatment consisting of saline injections. Each group was then compare to a group of four-month-old rats.

ScienceDaily reported that Dr Marbn stated that the cardiac stem cells secrete, tiny vesicles that are chock-full of signaling molecules such as RNA and proteins. Apparently, its the vesicles found in the young cells that, contain all the needed instructions to turn back the clock.

With these latest results, he said, Now we find that these specialized stem cells could turn out to reverse problems associated with aging of the heart.

The team is underway with more research, such as the ability to recreate the same results by administering the stem cells via IV (Intravenous) or with non-newborn cardiac stem cells. According to co-primary investigator and the first author of the study Lilian Grigorian-Shamagian, MD, PhD, their study didnt measure whether receiving the cardiosphere-derived cells extended lifespans. This will be another area the team plans to investigate.

References & Image Credits:(1) How NASA Anti-aging Drug Works(2) Science Daily(3) Wikipedia(4) LifeMapSC(5) OnlineJACC

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Cardiac Stem Cells May Be Fountain of Youth - Top Secret Writers

Cardiac Stem Cells Comments Off on Cardiac Stem Cells May Be Fountain of Youth – Top Secret Writers | September 1st, 2017

TAMPA (FOX 13) - Repairing a damaged heart has become much more than opening clogged arteries in the Cardiac Catheterization Lab at Pepin Heart Hospital in Tampa.

Dr. Charles Lambert and his team are injecting stem cells directly into specific areas in the walls of damaged hearts.

"We know where viable tissue is, what part of the heart is contracting and has live cells there," he explains.

Finding that living tissue begins with creating a color-coded map of the heart identifying areas where blood flow is maximized.

"We go back after mapping with a needle that comes out of the catheter and we do roughly twenty injections in viable tissue area," Lambert says.

It's all part of an experimental clinical trial Shiela Allen hopes will help her failing heart recover. Less than two hours after welcoming her youngest grandchild into this world, her grandson drove her to the emergency room.

"I couldn't breathe," she recalled.

Sheila was shocked when doctors told her that her heart was pumping at less than half of what it should.

"Now that I look back, I can figure out I had all the symptoms but I was just putting it off because I'm busy, I'm old, I'm a little bit overweight," she admits.

Like many women, Sheila ignored warning signs like fatigue, coughing and shortness of breath - especially when lying down.

"The coughing was odd to me because I was not congested, I could not lay flat in bed so I was propped up on four or five pillows," she says.

Similar to a balloon filled with too much water, the cardiac muscle is overstretched, thin, and weak. So weak, it can only pump a fraction of the blood inside its chambers to the rest of the body. That causes fluid to back up into the lungs and other parts of the body like the legs.

For about a decade, cardiologists have tried using stem cells to strengthen the muscle with mixed results. This study is hoping a new twist, will make it more successful.

Along with using the heart map to direct the injections, the stem cells are also different. Instead of taking them from the patient, syringes like these are filled with stem cells from donors.

"These trial cells are taken from healthy volunteers that are actually medical students, not here in town, but actually up in the northeast," he explains.

Another key difference in the study is the product's maker, Mesoblast. It is allowing people like Sheila, who have heart failure from unknown causes, to also enter the study. The clinical trial using the younger cells is now in 50 centers across the world.

"They're preserved so when we randomize a patient we take it off the shelf, treat it, warm it, the cells are perfectly alive and healthy and then administer it to the patients," Lambert says.

Side effects in earlier studies included a drop in blood pressure, bleeding, and fluid accumulation around the heart.

"It was basically like I was having another heart catheterization," Sheila says her side effects were minimal. "Three days after the procedure I was on a plane going on a trip."

She's not sure if she got a placebo or the actual cells, but as she completes her cardiac rehabilitation therapy, she says she is feeling better, "I've had a little more energy I dont know if it's related to that."

Energy allowing her to spend time with her family, and watch her youngest grandchild grow.

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Damaged hearts being repaired with stem cells - FOX 13 News, Tampa Bay

Cardiac Stem Cells Comments Off on Damaged hearts being repaired with stem cells – FOX 13 News, Tampa Bay | September 1st, 2017

Monkeys show reduced Parkinsonian symptoms following a donor-matched iPS cell-based therapy. Misaki Ouchida, Center for iPS Cell Research and Application, Kyoto University

One of the last steps before treating patients with an experimental cell therapy for the brain is confirmation that the therapy works in monkeys. In its latest study, the Jun Takahashi lab shows monkeys with Parkinson's disease symptoms show significant improvement over two years after being transplanted neurons prepared from human iPS cells. The study, which can be read in Nature, is expected to be a final step before the first iPS cell-based therapy for a neurodegenerative disease.

Parkinson's disease degenerates a specific type of cells in the brain known as dopaminergic (DA) neurons. It has been reported that when symptoms are first detected, a patient will have already lost more than half of his or her DA neurons. Several studies have shown the transplantation of DA neurons made from fetal cells can mitigate the disease. The use of fetal tissues is controversial, however. On the other hand, iPS cells can be made from blood or skin, which is why Professor Takahashi, who is also a neurosurgeon specializing in Parkinson's disease, plans to use DA neurons made from iPS cells to treat patients.

"Our research has shown that DA neurons made from iPS cells are just as good as DA neurons made from fetal midbrain. Because iPS cells are easy to obtain, we can standardize them to only use the best iPS cells for therapy, " he said.

To test the safety and effectiveness of DA neurons made from human iPS cells, Tetsuhiro Kikuchi, a neurosurgeon working in the Takahashi lab, transplanted the cells into the brains of monkeys.

"We made DA neurons from different iPS cells lines. Some were made with iPS cells from healthy donors. Others were made from Parkinson's disease patients," said Kikuchi, who added that the differentiation method used to convert iPS cells into neurons is suitable for clinical trials.

It is generally assumed that the outcome of a cell therapy will depend on the number of transplanted cells that survived, but Kikuchi found this was not the case. More important than the number of cells was the quality of the cells.

"Each animal received cells prepared from a different iPS cell donor. We found the quality of donor cells had a large effect on the DA neuron survival," Kikuchi said.

To understand why, he looked for genes that showed different expression levels, finding 11 genes that could mark the quality of the progenitors. One of those genes was Dlk1.

"Dlk1 is one of the predictive markers of cell quality for DA neurons made from embryonic stem cells and transplanted into rat. We found Dlk1 in DA neurons transplanted into monkey. We are investigating Dlk1 to evaluate the quality of the cells for clinical applications."

Another feature of the study that is expected to extend to clinical study is the method used to evaluate cell survival in the host brains. The study demonstrated that magnetic resonance imaging (MRI) and position electron tomography (PET) are options for evaluating the patient post surgery.

"MRI and PET are non-invasive imaging modalities. Following cell transplantation, we must regularly observe the patient. A non-invasive method is preferred," said Takahashi.

The group is hopeful that it can begin recruiting patients for this iPS cell-based therapy before the end of next year. "This study is our answer to bring iPS cells to clinical settings," said Takahashi.

This article has been republished frommaterialsprovided byCIRA, Kyoto University. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Monkeys With Parkinson's Disease Successfully Treated With Human Stem Cell Transplants - Technology Networks

IPS Cell Therapy Comments Off on Monkeys With Parkinson’s Disease Successfully Treated With Human Stem Cell Transplants – Technology Networks | September 1st, 2017

Stem cells and genome editing offer exciting opportunities within regenerative medicine. However, any clinical application of stem cells requires strict regulation to ensure that the cells are not exposed to animal derived products.

StemFit Basic02 is a xeno-free, defined medium for human pluripotent stem cell (hiPSC) culture that offers an effective solution for regenerative medicine research. This medium has been proven to effectively maintain Induced Pluripotent Stem (iPS) and Embryonic Stem (ES) cells under feeder-free conditions, during the reprogramming, expansion and differentiation phases of stem cell culture.

Specially formulated to enhance single cell expansion in the cloning step of stem cell genome editing, StemFit Basic02 offers superior and stable growth performance, high colony forming efficiency and robust scalable cell expansion. This ensures high karyotype stability over long periods and hence reproducible culture conditions.

StemFit cell culture media has been independently evaluated by CGT Catapult, an independent centre of excellence helping advance the UK cell and gene therapy industry. In these tests, StemFit not only delivered higher cell proliferation, but also showed characteristics such as homogeneity of gene expression compared with iPS cells cultured with 4 other media without any chromosomal abnormalities.

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Xeno-free Cell Culture Medium for Regenerative Medicine Research - Technology Networks

IPS Cell Therapy Comments Off on Xeno-free Cell Culture Medium for Regenerative Medicine Research – Technology Networks | September 1st, 2017

Stem cells and genome editing offer exciting opportunities within regenerative medicine.

However, any clinical application of stem cells requires strict regulation to ensure that the cells are not exposed to animal derived products.

Now Amsbio announces the availability of StemFit Basic02 feeder-free stem cell culture media.

StemFit Basic02 is a xeno-free, defined medium for human pluripotent stem cell (hiPSC) culture that offers an effective solution for regenerative medicine research.

This medium has been proven to effectively maintain Induced Pluripotent Stem (iPS) and Embryonic Stem (ES) cells under feeder-free conditions, during the reprogramming, expansion and differentiation phases of stem cell culture.

Specially formulated to enhance single cell expansion in the cloning step of stem cell genome editing, StemFit Basic02 offers superior and stable growth performance, high colony forming efficiency and robust scalable cell expansion.

This ensures high karyotype stability over long periods and hence reproducible culture conditions.

StemFit cell culture media has been independently evaluated by CGT Catapult, an independent centre of excellence helping advance the UK cell and gene therapy industry.

In these tests, StemFit not only delivered higher cell proliferation, but also showed characteristics such as homogeneity of gene expression compared with iPS cells cultured with four other media without any chromosomal abnormalities.

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Xeno-free cell culture medium for regenerative medicine research - Scientist Live

IPS Cell Therapy Comments Off on Xeno-free cell culture medium for regenerative medicine research – Scientist Live | September 1st, 2017

LONDON (Reuters)Scientists have successfully used reprogrammed stem cells to restore functioning brain cells in monkeys, raising hopes the technique could be used in future to help patients with Parkinsons disease.

Since Parkinsons is caused by a lack of dopamine made by brain cells, researchers have long hoped to use stem cells to restore normal production of the neurotransmitter chemical.

Now, for the first time, Japanese researchers have shown that human induced pluripotent stem cells (iPS) can be administered safely and effectively to treat primates with symptoms of the debilitating disease.

So-called iPS cells are made by removing mature cells from an individualoften from the skinand reprogramming them to behave like embryonic stem cells. They can then be coaxed into dopamine-producing brain cells.

The scientists from Kyoto University, a world-leader in iPS technology, said their experiment indicated that this approach could potentially be used for the clinical treatment of human patients with Parkinsons.

In addition to boosting dopamine production, the tests showed improved movement in affected monkeys and no tumors in their brains for at least two years.

The human iPS cells used in the experiment worked whether they came from healthy individuals or Parkinsons disease patients, the Japanese team reported in the journal Nature on Wednesday.

This is extremely promising research demonstrating that a safe and highly effective cell therapy for Parkinsons can be produced in the lab, said Tilo Kunath of the MRC Centre for Regenerative Medicine, University of Edinburgh, who was not involved in the research.

The next step will be to test the treatment in a first-in-human clinical trial, which Jun Takahashi of Kyoto University told Reuters he hoped to start by the end of 2018.

Any widespread use of the new therapy is still many years away, but the research has significantly reduced previous uncertainties about iPS-derived cell grafts.

The fact that this research uses iPS cells rather human embryonic stem cells means the treatment would be acceptable in countries such as Ireland and much of Latin America, where embryonic cells are banned.

Excitement about the promise of stem cells has led to hundreds of medical centers springing up around the world claiming to be able to repair damaged tissue in conditions such as multiple sclerosis and Parkinsons.

While some treatments for cancer and skin grafts have been approved by regulators, many other potential therapies are only in early-stage development, prompting a warning last month by health experts about the dangers of stem-cell tourism.

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Human Stem Cells Fight Parkinson's Disease in Monkeys - Scientific American

Skin Stem Cells Comments Off on Human Stem Cells Fight Parkinson’s Disease in Monkeys – Scientific American | September 1st, 2017

Microneedling has quickly become one of the most popular skin rejuvenation treatments. If youre considering trying it, here is what you need to know.

Microneedling, also called collagen-induction therapy, uses small needles that pierce the outermost layer of skin to create tiny microchannels. These microchannels help stimulate the production of collagen and elastin within the skin. They also promote new capillaries.

This can lead to an improved skin texture, reduction of acne or other scarring and help with discoloration, such as brown spots caused by sun damage. Microneedling may be combined with platelet-rich plasma, stem cells, or pure hyaluronic acid to enhance results further.

Microneedling can also be used on the scalp to help stimulate hair rejuvenation.

Prior to your first microneedling session, you will be asked to avoid sun exposure for at least 24 hours. Some doctors will tell you to avoid blood-thinning medications and herbal supplements like aspirin, ibuprofen, and St. Johns wort to reduce bruising.

Each microneedling session takes about 20 to 30 minutes. First, your face will be cleansed and a numbing cream will be applied. Multiple treatment sessions, spaced a few weeks apart, are recommended. Most doctors recommend three to six treatments but many will notice an improvement in the tone and texture of their skin after just one treatment.

Immediately after your microneedling session, you will likely notice some redness that can last for several days. In my practice, we recommend that patients do not touch their face for at least four hours after treatment and not to apply anything to the face for 24 hours. It is crucial to avoid sun exposure for three days after the procedure.

You should avoid strenuous activity and exercise for the first 12 hours after treatment to prevent redness and bruising. For the first three days after treatment, you should use a gentle non-foaming cleanser, a barrier repair moisturizer, and a physical SPF. If swelling or bruising are a concern, you can take arnica supplements both before and after treatment to help minimize these side effects.

Once any redness or swelling diminishes, you should notice an immediate improvement in the way your skin looks and feels. Over the next several weeks, your skins appearance should continue to improve.

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Here's What You Need to Know about Microneedling - Miami Herald

Skin Stem Cells Comments Off on Here’s What You Need to Know about Microneedling – Miami Herald | September 1st, 2017