February 18, 2017 at 1:00 am | By Lisa Turpin Special to the News-Press

National Donor Day, observed on Feb. 14, is a great time to register as an organ, eye, and tissue donor or to make an appointment to donate blood or platelets.

What could show more love on Valentines Day than the act of giving ones body to help another?

Whether you are a living donor of blood products, stem cells, kidney or liver, register with your state as an organ donor, or make the decision for your loved one to be a donor, you are truly giving the gift of life.

Nationally, more than 119,000 people are waiting for an organ transplant, including 2,091 children.

That doesnt include the number waiting for a bone marrow (stem cell) matched donor which is much more complicated to find.

Significant progress continues in the advancement of transplantation medicine with goals of lengthening life spans, restoring function, appearance, and quality of life.

But it still takes the generosity of donors and their loved ones to make a transplant possible.

Claudia Swigart of Pinehurst believes the true value of organ donation is the gift of time.

In her case, fifteen years with her husband Wendell that she, their five combined children, thirteen grandchildren, and twelve great-grandchildren may not have had.

Wendell and his three siblings all had Polycystic Kidney Disease (PKD), an inherited condition causing cysts to form in the kidney causing damage and kidney failure.

Wendell worked in the mine here in the Valley, shares Claudia.

He found out he had Polycystic Kidney Disease when he was thirty-four and he was careful, he exercised, ate healthy and never smoked. He didnt have any kidney problems until he was sixty-three and had to have open heart surgery.

The surgery was hard on Wendell and his lungs collapsed, he nearly died and it put his kidneys in distress.

He started dialysis after that and was eventually put on the kidney transplant list to receive a transplant at Sacred Heart Medical Center.

The dialysis center in Pinehurst had not opened, so Claudia drove Wendell to Coeur dAlene two times a week for three-hour treatments.

Claudia shared, I am so thankful they opened a dialysis center here. Its exhausting enough to be on dialysis without the traveling.

But there is more to this story.

We always liked telling everyone we could about what happened because we knew God had His hand in the plan, explains Claudia.

They normally traveled to Arizona in their camper for the winter.

Wendell would arrange to have dialysis at the center in Arizona instead of Coeur dAlene.

Well, in 2001 we were planning on leaving so Wendell called to remove himself from the transplant list while we were gone. But, when he called to arrange dialysis at the center in Arizona, they were full! said Claudia.

Since Wendell couldnt have dialysis in Arizona, they were forced to stay home which meant he remained on the transplant list.

Just a few weeks later we got the call! Claudia exclaimed.

Wendell was told he had a matched kidney on the way from a donor in Alaska.

Wendell was sixty-five at the time and he asked if there were any younger people waiting for transplants, anyone still raising young kids who needed it more than he did. His doctor knew he was that kind of man and firmly told him that it was Wendells kidney and he was taking it!

Wendells kidney was such a good match he never experienced any problems or symptoms of rejection.

The transplant coordinators said that the Swigarts could write a letter to the donors family in Alaska if they wanted to have communication with them or thank them.

We wrote a letter to the family two months later and Wendell told them he would take real good care of the kidney, Claudia said.

Wendell did take great care of himself but unfortunately fought esophageal cancer unrelated to his kidneys and passed away in March of 2016 at the age of 80.

The donors family never wrote back, so they do not know the identity of the donor, but Claudia and Wendell were glad they sent the thank-you letter.

We went back to Arizona the year after the transplant and didnt have to worry about dialysis any more. We may never have gotten to do that and he sure wouldnt have had the life he had without the generosity of the donor and their family.

Wendell Swigart had 15 extra quality years with his bride and they celebrated their forty-sixth wedding anniversary before his passing.

Statistics say that only three out of 1,000 people who die are candidates for organ donation, and thats if their families agree to donation.

Even if you register as a donor, it is still up to your family to make the final decision.

Making your family aware that you want to be a donor is the most important thing you can do. For more information visit http://www.donatelife.net or http://www.Organize.org.

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Giving the Gift of Life ~ National Donor Day - Shoshone News Press

Bone Marrow Stem Cells Comments Off on Giving the Gift of Life ~ National Donor Day – Shoshone News Press | February 20th, 2017

A MAN who narrowly missed out on a heart transplant has become the first patient in Europe to receive a revolutionary new treatment on compassionate grounds.

Gordon Foster, 59, suffered the first of a number of heart attacks at 30, and was advised he would need a heart transplant.

But as his heart functionality was working at 17 per cent, he was not eligible for the transplant which requires functionality at below 16 per cent.

Gordon, a welder, was then made redundant and became depressed.

His poor health meant he became housebound and, at times, was unable to move from one room to the next.

But his life has now been transformed as he has become the first patient in Europe to undergo stem cell treatment to regenerate part of his heart muscle through the new Compassionate Treatment Programme at St Bartholomews Hospital in London.

The treatment meant Gordon was given injections to stimulate the growth of his own stem cells. Bone marrow was then taken and the stem cells extracted from it before being injected back into his heart to regenerate the muscle.

Within a week of the operation, Gordon no longer needed to use his stair lift, his daily tasks such as walking up the stairs and doing housework became easier and he was able to enjoy spending time with his wife and children.

Gordon, who lives in Bridlington, said: I will forever be thankful to the Heart Cells Foundation, and the work of the team at St Bartholomews Hospital, as without them I believe I wouldnt be here today and Im enjoying every moment I spend with my wife and children.

Not only has the stem cell treatment I received helped to improve my physical health, but it has also massively improved my mental health and I now live every day with hope for the future.

Professor Anthony Mathur, consultant at St Bartholomews Hospital, said: Gordons story proves just how important it is to offer cell therapy to those who have no other medical choice.

With more than a million people suffering with heart disease and failure in the UK, the need for treatment in this field has never been greater.

We hope to lead the way to the treatment ultimately being available to thousands of other patients through the NHS, so we can help people like Gordon to lead near normal lives again.

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New start for stem cell heart op man, Gordon - The Press, York

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Slacking off in ALS? Mutant SOD1 may partially close the SLACK ion channel resulting in increased excitability in some neurons (Zhang et al., 2017).[Image: NIGMS.]

Increased activity in the motor cortex of the brain may occur in most forms of ALS (see September 2015 news). But whether this hyperexcitability contributes to the disease remains an open question.

Now, researchers at Yale University make the case that ALS-linked mutant SOD1 may downregulate a key sodium-gated potassium ion channel, known as SLACK, through an apoptosis signal-regulatingkinase1 (ASK1)-based mechanism (Zhang et al., 2017).

The findings may help explain how motor neuron hyperexcitability occurs in ALS. These changes in excitability may contribute to disease pathogenesis and may underlie fasciculations, one of the earliest clinical manifestations of the disease.

The question is whether this pathway is the primary way that SOD1 mutations cause disease, said Steve Vucic of the University of Sydney, who was not involved in the study. If so, [there] is a tremendous opportunity for developing treatments against these kinase pathways.

The study is published on January 24 in the Journal of Neuroscience.

Excitement builds

Neuronal hyperexcitability emerged in recent years as an early and potentially unifying stepin ALS, due to its detection in a number of sporadic and genetic forms. While the evidence is still not yet conclusive, some studies suggest that this prolonged excitation can lead to toxicity, strengthening the case that these changes in excitability may contribute to the disease (Fritz et al., 2013; Hadzipasic et al., 2014).

How hyperexcitability occurs in ALS remains unclear. But a growing number of studies suggest that mutant SOD1 may be involved, at least in some cases of the disease (Wainger et al., 2014; van Zundert et al., 2008).

Researchers at Yale University, led by Leonard Kaczmarek and Arthur Horwich, wondered whether mutant SOD1 could trigger hyperexcitability in motor neurons by downregulating a key membrane-bound ion channel called SLACK (sequence like a calcium-activated K channel), also known as KCNT1 or KNa1.1.

SLACK is a key regulator of excitability that helps neuronsreturn to the resting state upon firing. Its widely expressed in the CNS and its dysfunction has also been implicated in neurological diseases including Fragile X and epilepsy (Barcia et al., 2012; Heron et al., 2012; Martin et al., 2014).

Hyperexcitability in the bag. Researchers use sea slug bag cell neurons to study underlying hyperexcitability mechanisms. [Image: Kabir et al., 2001 under a CC-BY-NC-SA license.]

To investigate this question, first co-authors Yalan Zhang and Weiming Ni turned to the neuronalmodel system, the sea slug Aplysia. The system gained recognition in the 1960s for its role in providing Eric Kandel Nobel Prize-winning insights into learning and memory formation.

The approachinvolves the manipulation and study of bag cell neurons, very large neuroendocrine cells in the sea slugs abdomen that control egg laying. The really big advantage is that, because of their size, you can inject materials into them and then use a very fine microelectrode to record changes in excitability, all without any disturbance of the cytoplasm, Kaczmarek said.

The researchers compared the activity of potassium channels in bag cell neurons in the presence or absence of wild-type or mutant SOD1, including soluble oligomers of increasing size. They found that SOD1 or mutant SOD1 G85R monomers had no effect. But when they injected SOD1 G85R oligomers, they observed a reduction in outward potassium currents by 20-30%. This drop occured within 10 minutes and increased with larger oligomer size.

Whats more, SOD1 G85R oligomers increased excitability of these neurons. Injection of these soluble 300 kDa protein complexes decreased the neurons resting membrane potential and increased its susceptibility to firing in response to applied stimuli, they found.

Further experiments identified the SLACK channel as the one most likely to have been affected by mutant SOD1, because neurons pretreated with siRNA against SLACK mitigated the effect of these protein complexes in these neurons.

Together, the results suggest that soluble mutant SOD1 oligomericcomplexes may lead to hyperexcitability due to partial closure of SLACK, a key sodium-gated potassium channel that helps neurons return to their resting state upon firing.

ASK1ing for trouble

How could mutant SOD1 downregulateSLACK? The researchers suspected that these effects may be triggered by ASK1, a key kinase that has been previously implicated in the destruction of motor neurons in the disease (Raoul et al., 2002).

ASK1 has been shown to mediate key effects of mutant SOD1 in mouse models of the disease including ER stress and disruption of axonal transport (Lee et al., 2016; Song et al., 2013). In addition, inhibitingthis pathway appears to extend the survival of a SOD1 G93A mouse model of the disease (Fujisawa, et al. 2016).

To investigate this possibility, the researchers blocked ASK1 signaling and determined the impact of SOD1 oligomeric complexes on potassium channel activity. They found that the suppression of outward potassium current could be abolished by pre-treatment with an inhibitor of the apoptosis signaling regulating kinase ASK1. Similar effects were achieved with an inhibitor of one of ASK1s downstream targets, JNK.

The results, Kaczmarek said, suggest that mutant SOD1 oligomericcomplexessuppressSLACK channels in neurons through a ASK1-based mechanism, causing hyperexcitability.

Its an attractive idea, says Massachusetts General Hospitals Brian Wainger, who was not involved in the study. The findings may provide a potentially direct mechanistic connection between mutant SOD1 and motor neuron hyperexcitability in ALS.

Mind your Potassium and KCNQs. Researchers are evaluating Kv 7.2 potassium channel activators including retigabine (orange) in hopes to reduce hyperexcitability in people with the disease. More specific channel modulators are being developed. One such activator, AUT00063, is being evaluated at the phase 2a stage by the London startup Autifony Therapeutics to treat hearing disorders. [Miceli et al., 2011 under CC BY 4.0 license.]

But a change in excitability may not be the only or even the most important consequence of SLACK down regulation, according to Kaczmarek. SLACK may act as an activity sensor, providing a direct link between neuronal firing and protein synthesis.

His teamhas previously shown that SLACK channel activity plays a role in synaptic development, through its ability to regulateactivity-dependent protein synthesis (Brown et al., 2010; Zhang et al., 2012). When you precipitate the channel from mammalian brain, it pulls down several messenger RNAs, he pointed out, and mutations that cause channel overactivity are associated with epilepsy (Barcia et al., 2012; Kim et al., 2015).

In fact, Kaczmarek added, it may not be the hyperexcitability of motor neurons that is toxic in ALS, but rather its proposed (but not yet tested) consequences on protein synthesis. A rapid change in the activity of these channels, as we saw here, is likely going to alter protein synthesis, and that can produce much longer-lasting effects, potentially more consistent with a late-onset disease.

This was an extremely elegant study, and an ingenious way to approach the issue of hyperexcitability, said Steve Vucic, who, in collaboration with University of Sydneys Matthew Kiernan in Australia helped identify these neuronal changes as an early sign of ALS in people with the disease. The goal now will be to see if this same pathway is affected in the mammalian models, or in human ALS iPS cells.

Brian Wainger agrees. The key questions, according to Wainger, are whether these findings hold up in mammalian models, and whether these findings can be generalized to other forms of the disease.

Searching for ALS-linked gene variants in SLACK or related ion channels might also provide insight into its relevance for the human disease, added Vucic.

Approaching the clinic

Hyperexcitability is clearly a clinical feature of many forms of familial and sporadic ALS, explains Wainger. Thats why it is attractive as a convergent mechanism for many forms of ALS. But one of the challenges is to determine to what extent an increase in firing is relevant for disease pathogenesis, rather than, as some argue, being a compensatory mechanism. Directly modulating excitability is one of the clearest ways of answering that question directly, he added.

If motor neuron hyperexcitabilitydoes hold up as a driver of disease, however, it may be a good target for therapy, according to Kaczmarek. I see this as very much a therapeutic possibility.

The reason is because opening up these potassium ion channels may help motor neurons in people with ALS return to their resting state and thereby, reduce hyperexcitability in the disease.

Finding magneto. Researchers are using transcranial magnetic stimulation to evaluate in part whether mexiletine and retigabine reduce hyperexcitability in people with the disease.[Image: NIH].

Kaczmareks team is now hoping to do just that by developing a SLACK activator. The project is ongoing.

In the meantime, clinicians are aiming to reduce hyperexcitability in people with ALS by repurposing existing medicines in hopes to treat the disease. Brian Wainger is leading an effort to determine whether the epilepsy drug retigabine may be helpful in ALS. The drug, identified by Wainger as a potential treatment while in the laboratory of Kevin Eggan, may help normalize the activity of motor neurons by opening up Kv7 potassium channels in people with the disease (see April 2016 news; ; Wainger et al., 2014).

Across the US, the University of Washingtons Michael Weiss is taking a different approach. He is evaluating whether mexiletine, a sodium channel blocker, may reduce hyperexcitability in people with the disease (see March 2016 news). Both strategies are currently at the phase 2 stage.

In a disease that has a selective neuronal vulnerability like ALS, says Wainger, I think it is likely that the electrophysiological properties of the neuron are going to be related to the degenerative nature of the disease. So normalizing those properties may have a good chance of being helpful.

References

Zhang Y, Ni W, Horwich AL, Kaczmarek LK. AnALS-associatedmutantSOD1rapidlysuppressesKCNT1 (Slack) Na+-activated K+ channels in Aplysia neurons. J Neurosci. 2017 Jan 24. pii: 3102-16. [PubMed]

Fritz E, Izaurieta P, Weiss A, Mir FR, Rojas P, Gonzalez D, Rojas F, Brown RH Jr, Madrid R, van Zundert B. MutantSOD1-expressing astrocytes release toxic factors that trigger motoneuron death by inducing hyperexcitability. J Neurophysiol. 2013 Jun;109(11):2803-14. 2013 Mar 13. [PubMed].

Hadzipasic M, Tahvildari B, Nagy M, Bian M, Horwich AL, McCormick DA. Selective degeneration of a physiological subtype of spinal motor neuron in mice with SOD1-linked ALS. Proc Natl Acad Sci U S A. 2014 Nov 25;111(47):16883-8. [PubMed].

Wainger BJ, Kiskinis E, Mellin C, Wiskow O, Han SS, Sandoe J, Perez NP, Williams LA, Lee S, Boulting G, Berry JD, Brown RH Jr, Cudkowicz ME, Bean BP, Eggan K, Woolf CJ.Intrinsic membrane hyperexcitability of amyotrophic lateral sclerosis patient-derived motor neurons. Cell Rep. 2014 Apr 10;7(1):1-11.[PubMed]

van Zundert B, Peuscher MH, Hynynen M, Chen A, Neve RL, Brown RH Jr, Constantine-Paton M, Bellingham MC. Neonatal neuronal circuitry shows hyperexcitable disturbance in a mouse model of the adult-onset neurodegenerative disease amyotrophic lateral sclerosis. J Neurosci.2008 Oct 22;28(43):10864-74. [PubMed].

Barcia G, Fleming MR, Deligniere A, Gazula VR, Brown MR, Langouet M, Chen H, Kronengold J, Abhyankar A, Cilio R, Nitschke P, Kaminska A, Boddaert N, Casanova JL, Desguerre I, Munnich A, Dulac O, Kaczmarek LK, Colleaux L, Nabbout R. De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy. Nat Genet. 2012 Nov;44(11):1255-9. [PubMed].

Heron SE, Smith KR, Bahlo M, Nobili L, Kahana E, Licchetta L, Oliver KL, Mazarib A, Afawi Z, Korczyn A, Plazzi G, Petrou S, Berkovic SF, Scheffer IE, Dibbens LM. Missense mutations in the sodium-gated potassium channel gene KCNT1 cause severe autosomal dominant nocturnal frontal lobe epilepsy. Nat Genet. 2012 Nov;44(11):1188-90. [PubMed].

Martin HC, Kim GE, Pagnamenta AT, Murakami Y, Carvill GL, Meyer E, Copley RR, Rimmer A, Barcia G, Fleming MR, Kronengold J, Brown MR, Hudspith KA, Broxholme J, Kanapin A, Cazier JB, Kinoshita T, Nabbout R; WGS500 Consortium., Bentley D, McVean G, Heavin S, Zaiwalla Z, McShane T, Mefford HC, Shears D, Stewart H, Kurian MA, Scheffer IE, Blair E, Donnelly P, Kaczmarek LK, Taylor JC. Clinical whole-genome sequencing in severe early-onset epilepsy reveals new genes and improves molecular diagnosis. Hum Mol Genet. 2014 Jun 15;23(12):3200-11. [PubMed].

Raoul C, Estvez AG, Nishimune H, Cleveland DW, deLapeyrire O, Henderson CE, Haase G, Pettmann B. Motoneuron death triggered by a specific pathway downstream of Fas. potentiation by ALS-linked SOD1 mutations. Neuron. 2002 Sep 12;35(6):1067-83. [PubMed].

LeeS, Shang Y, Redmond SA, Urisman A, Tang AA, Li KH, Burlingame AL, Pak RA, Jovii A, Gitler AD, Wang J, Gray NS, Seeley WW, Siddique T, Bigio EH,LeeVM, Trojanowski JQ, Chan JR, Huang EJ. Activation of HIPK2 Promotes ER Stress-Mediated Neurodegeneration in Amyotrophic Lateral Sclerosis. Neuron. 2016 Jul 6;91(1):41-55. [PubMed].

Song Y, Nagy M, Ni W, Tyagi NK, Fenton WA, Lpez-Girldez F, Overton JD, Horwich AL, Brady ST. Molecular chaperone Hsp110 rescues a vesicle transport defect produced by an ALS-associated mutant SOD1 protein in squid axoplasm. Proc Natl Acad Sci U S A. 2013 Apr 2;110(14):5428-33. [PubMed].

Fujisawa T, Takahashi M, Tsukamoto Y, Yamaguchi N, Nakoji M, Endo M, Kodaira H, Hayashi Y, Nishitoh H, Naguro I, Homma K, Ichijo H. The ASK1-specific inhibitors K811 and K812 prolong survival in a mouse model of amyotrophic lateral sclerosis. Hum Mol Genet. 2016 Jan 15;25(2):245-53. [PubMed].

Brown MR, Kronengold J, Gazula VR, Chen Y, Strumbos JG, Sigworth FJ, Navaratnam D, Kaczmarek LK. Fragile X mental retardation protein controls gating of the sodium-activated potassium channel Slack. Nat Neurosci. 2010 Jul;13(7):819-21. [PubMed].

Zhang Y, Brown MR, Hyland C, Chen Y, Kronengold J, Fleming MR, Kohn AB, Moroz LL, Kaczmarek LK. Regulation of neuronal excitability by interaction of fragile X mental retardation protein with slack potassium channels. J Neurosci. 2012 Oct 31;32(44):15318-27. [PubMed].

Kim GE, Kronengold J, Barcia G, Quraishi IH, Martin HC, Blair E, Taylor JC, Dulac O, Colleaux L, Nabbout R, Kaczmarek LK. Human slack potassium channel mutations increase positive cooperativity between individual channels. Cell Rep. 2014 Dec 11;9(5):1661-72. [PubMed].

disease-als hyperexcitability mexiletine retigabine SOD1 topic-preclinical topic-researchmodels

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A key ion channel may SLACK off in ALS - ALS Research Forum

IPS Cell Therapy Comments Off on A key ion channel may SLACK off in ALS – ALS Research Forum | February 20th, 2017

VAIL Hallways at the world-famous Steadman Clinic are lined with framed, autographed jerseys of star athletes who have had surgery here, including John Elway, Mario Lemieux and Alex Rodriguez.

The clinic and its associated Steadman Philippon Research Institute (SPRI) attract world-class talent from all fields including U2 drummer Larry Mullen Jr., who joined the institutes board after he was a patient here but perhaps its top recruit was a renowned scientist researching ways to help injuries heal faster and slow down the way our bodies age.

Were trying to develop the iPhone 9 of medicine, said Dr. Johnny Huard, chief scientific officer and director of the institutes Center for Regenerative Sports Medicine. Your iPhone 6 and 7 are great, its doing everything you want, but youre looking on the web at what the iPhone 8s going to do. We want to have surgeons here doing surgery on our best football, hockey, basketball players, and instead of losing a year to heal, can we heal them in six months? Three months? Would that be great?

Joe Amon, The Denver Post

The field is called biologics, and its transforming orthopedics by using cells that heal produced in the patients body in concentrated injections that can hasten tissue repair directly at the site of the injury. Huard is leading cutting-edge research into stem cells and platelet-rich plasma (PRP) therapy that he believes will some day delay age-related diseases and cut the recovery time from serious injuries, such as to the knee, in half.

Stem cells are undifferentiated cells that can become specialized cells muscle, bone, cartilage to help repair tissue. Platelets carry proteins that help in the healing process. The breakthroughs Huard and his colleagues are pursuing hold exciting promise for weekend warriors as well as for star athletes.

I dont think we can reverse aging, but I think we can age better and recover from injury better, said Dr. Marc Philippon, managing partner of the Steadman Clinic and co-chairman of the research institute. As a surgeon my biggest challenge is, if I cut on you theres always that healing phase. We want to recover faster. But the most important thing is prevention of injury. If your cells are aging better, youll have less injury. The way I look at it, thats going to put us out of business, but thats OK. Its a good way to go out of business.

A world-class scientist, Huard discovered muscle-derived stem cells in 1998. Before joining SPRI two years ago he was the director of the Stem Cell Research Center at the University of Pittsburgh.Researchers here believe injections of stem cells and PRP can help delay or prevent the need for joint replacements, and at the adjacent clinic they can test their theories in clinical trials. They have shown in animal studies that young stem cells can rejuvenate old stem cells.

To that end Huard advocates passionately that when a child is born, stem cells from the umbilical cord should be harvested and frozen at minus-80 degrees Fahrenheit. As bodies age, stem cells diminish in number and vitality, but they can be preserved in suspended animation while frozen. Those cells later can be thawed and reintroduced into the body as younger and more robust stem cells than the ones that have aged in the patient, performing like a fountain of youth.

Thats the best gift you can give to that baby, said Huard, a French Canadian with a playful wit. Its the best gift you can give to that mother, too, because that (umbilical cord) is part of her, too. Its not only part of the baby. Can you believe the impact of that?

Stem cells, aging and exercise

Because stem cells can develop into every cell type in the body, researchers believe they can be used to hasten repair of nerves, bone and muscle. Bone marrow transplants are the most common form of stem cell therapy currently in use, but stem cells may be useful in fighting neurodegenerative diseases and other conditions.

We can use them to repair bone, cartilage, the heart, the bladder, Huard said. We have clinical trials now ongoing for bladder and the heart.

Imagine a Broncos running back blowing out his anterior cruciate ligament in training camp but being able to return to the field during the regular season. Huardforesees that day, as well as a time when patients whose stem cells were harvested and stored at birth will be able to have them injected into their knees decades later after ACL repair, for example, which theoretically could allow the person to recover much faster.

If I harvest stem cells from your muscle today, lets say I find 100 stem cells, but if I do the same thing 30 years ago I may have gotten 10,000, Huard said. Not only that, but the 100 stem cells you have are tired. They have been dividing and trying to repair your muscle.

When one of Huards children was born 17 years ago and it came time for Huard to cut the umbilical cord, he asked the nurse what they were going to do with it.

My wife said, Can you stop being a scientist and be my husband for a minute here? Huard tells the story with amusement, but he is passionate that umbilical cord stem cells should be saved.

I tell people, No more flowers, just freeze the stem cells from that newborn, Huard said. Thats the best gift you can give to that kid.

In the meantime, Huard believes exercise remains the best anti-aging mitigation we have. Beyond the benefits already well known, he is convinced exercise increases the production of stem cells and delays the aging process.Researchers found that mice that run on treadmills heal significantly faster than sedentary mice. Mice who exercised also had a better survival rate after being injected with cancer cells than those that were sedentary.

Huardbelieves exercise helps the brain as well as the heart in ways that might not be fully understood but might have implications for the prevention or delay of dementia and Alzheimers.

Stem cells come from blood vessels, Huard said. What can we do to increase the number of blood vessels? If we can do that, then we can probably improve tissue repair. If you exercise, you increase the number of blood vessels in your tissues.

Platelet-rich plasma therapy

PRP therapy is already in widespread use, not just in elite athletes but in recreational athletes as well. Sometimes it works well, and sometimes it doesnt work at all. Huard is trying to find out why.

Platelets in the blood carry proteins called growth factors that help the body repair injured tissue. In PRP therapy, a patients blood is removed and spun in an centrifuge or filtered to separate platelets. Then the platelet-rich plasma is injected into the site of an injury with hopes of speeding the healing process.

When you injure something, you bleed, Philippon said in his office with a view of Vails ski trails. Some of the first elements going there are your platelets, and theres a reason for that. Platelets have the growth factors, also what we call the chemotactic factors, to attract whats needed (to heal).

Philippon has used PRP to hasten healing of hip tendons in football players, for example.

What we found was that those I injected with PRP early recovered faster, Philippon said. We have that data here. We know, for a tendon injury, PRP is a great therapy.

Huard had elbow surgery last year after snapping a tendon off the bone in a ski accident I like to go fast, he said with a grin and Steadman surgeon Peter Millett asked Huard if he wanted a PRP injection in hopes of hastening recovery.

I said, Of course! You know what? I never wore a sling, Huard said. The week after, I was running. Three weeks after, I was back skiing.

But did the PRP help?

I dont know, Huard said.

So Huard is studying the success rate of PRP therapy in patients who receive it after surgery at the Steadman Clinic. When Philippon uses PRP on a patient, for example, he will set aside a fraction of that PRP and give it to Huard to analyze in the lab. Huard will catalog the different growth factors in each sample and then wait to see how the patients respond.

After this Im going to go back to Marc and say: Which patient worked? Which one was your best patient? Huard said. If he tells me patient No. 24 and 32 and 48, Im going to go back and try to see what those three patients PRP had in common in terms of growth factors.

Then Huard will be able to better advise surgeons before using PRP.

Lets say we find when IGF1 (insulin growth factor one) is high in your blood, PRP always works, Huard said. You know what Im going to give to those surgeons? Im going to say, Before you give PRP, take a blood draw, we go in the lab, test for IGF1, and if IGF1 is high, 95 percent chance PRP is going to help. But another patient, if IGF1 is not high, Based on our tests, I dont think PRP is going to help.

Another thing we found in PRP, it is a mixed bag. You have good things in PRP but you have bad things, too. So were doing science where Im going to take PRP, Im going to take out the bad guys.

As with stem cells, Huard foresees a day when a young patients PRP can be frozen and used decades later to delay aging, administered in conjunction with stem cell injections to work in synergy.

I think the two can be combined somehow, Huard said. They are different, but the stem-cell therapy and the PRP somehow can be together. If I have your PRP from 20 years ago and I have your stem cells from 20 years ago, I can make a very nice mixture, inject this into you. Sometimes adding one thing to another, biologically, it equals not two but three.

Having his laboratory in the same building as the Steadman Clinic, which has eight surgeons on staff, is a boon for Huard in his research. He takes ideas to them and vice versa.

I dont do science just to do science, he said. I do science to improve quality of life, and I think I can make a major contribution in the field. If you delay aging by 10 years, you delay all those age-related disorders by 10 years. The implications for health care is amazing.

Biologics: Using tools produced by a patients body such as stem cells and platelet-rich plasma (PRP) to help the patient heal faster and better.

Regenerative medicine: This and tissue engineering are promising treatment approaches that can enhance or promote musculoskeletal tissue healing and regeneration following surgery or injection therapy. Biological treatments such as growth factor supplementation, PRP and bone marrow concentrate have been shown to improve patient function and quality of life.

Platelet-rich plasma: A biologic treatment that is produced by concentrating the patients own blood to yield a high platelet count. Platelets are important blood components that secrete hundreds to thousands of biological factors that initiate musculoskeletal tissue healing and regeneration.

Stem cells: Stem cells have the ability to transform into specific musculoskeletal tissue cells. These types of cells also secrete biological factors that initiate musculoskeletal tissue healing and regeneration. There are several forms of stem cells, such as muscle-derived stem cells, bone marrow-derived stem cells, adipose-derived stem cells and others.

John Meyer, The Denver Post

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How researchers in Vail are pursuing breakthroughs to help injuries heal faster and some day slow down the way ... - The Denver Post

Bone Marrow Stem Cells Comments Off on How researchers in Vail are pursuing breakthroughs to help injuries heal faster and some day slow down the way … – The Denver Post | February 19th, 2017

Researchers in Germany have discovered that a tumor suppressor protein thought to prevent acute myeloid leukemia (AML) can actually promote a particularly deadly form of the disease. The study, "RUNX1 cooperates with FLT3-ITD to induce leukemia," which will be published online February 17 in The Journal of Experimental Medicine, suggests that targeting this protein could be an effective treatment for certain AML patients.

AML accounts for over 1 percent of all cancer deaths in the United States and is characterized by an excessive proliferation of hematopoietic stem cells in the bone marrow and their subsequent failure to differentiate into white blood cells. AML can be caused by various combinations of gene mutations. One of the most common mutations is in the gene encoding the cell surface signaling protein FLT3, and patients with this mutation show poor rates of survival. The mutant form of FLT3 can promote cell proliferation, but experiments in mice have shown that it isn't sufficient to block white blood cell differentiation and induce AML on its own.

Carol Stocking and colleagues at the Heinrich-Pette-Institute, Leibniz Institute for Experimental Virology in Hamburg noticed that many patients carrying the mutant form of FLT3 also showed increased levels of a transcription factor called RUNX1. "This was unexpected because up to 20 percent of AML patients carry mutations that inactivate RUNX1, which is generally considered to be a tumor suppressor that prevents the formation of leukemias," Stocking says.

Stocking's team found that reducing RUNX1 levels attenuated the ability of human AML cells expressing mutant FLT3 to form tumors when injected into mice. In contrast, elevated RUNX1 levels worked with mutant FLT3 to induce AML. Mouse hematopoietic stem cells expressing mutant FLT3 were highly proliferative, and co-expression of RUNX1 blocked their differentiation, allowing them to give rise to AML.

Mutant FLT3 appears to stabilize and activate RUNX1 by promoting the transcription factor's phosphorylation. Active RUNX1 then blocks white blood cell differentiation, at least in part, by inducing another transcription factor called Hhex. Hematopoietic stem cells expressing both Hhex and mutant FLT3 also gave rise to AML, the researchers found.

RUNX1 may therefore suppress the initiation of AML but, after being activated by mutant FLT3, block white blood cell differentiation and promote tumor development. "Therapies that can reverse this differentiation block may offer significant therapeutic efficacy in AML patients with FLT3 mutations," says Stocking. "Ablating RUNX1 is toxic to leukemic cells but not to normal hematopoietic stem cells, so inhibiting RUNX1 may be a promising target in combination with FLT3 inhibitors."

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Tumor suppressor promotes some acute myeloid leukemias, study reveals - Science Daily

Bone Marrow Stem Cells Comments Off on Tumor suppressor promotes some acute myeloid leukemias, study reveals – Science Daily | February 19th, 2017

Asterias Biotherapeutics (AST) continues to generate excitement and buzz around its stem cell treatment for catastrophic spinal cord injury (SCI). I wrote about this historic event back in September. Thats when the company first released results about this transformative medical breakthrough.

Asterias has now released follow-up data. This was gathered at six and nine months after six quadriplegics received treatment. All six continue to show improvement in motor function and sensation. This is truly wonderful news for those with SCI.

There are also broader medical implications and these should be of great interest to investors.

The difference between this stem cell therapy and traditional drug therapies is huge. Drug therapies have specific and mechanistic impacts. But stem cells derived from embryonic cells work a different way. They draw on the massive DNA databanks in their nuclei. They then use these genetic programs to interact with their surroundings and repair damaged structures.

The Asterias oligodendrocyte progenitor cells were derived from a single unused embryo (from an IVF procedure in the late 1990s). Such embryos are often discarded. But this one was donated to create an unlimited number of therapeutic cells. Both the Bush and Obama Administrations approved the cell line.

When injected into the site of a spinal cord injury, these cells create healthy new spinal cord structures. They restore myelin sheaths (which are like an insulating material on nerves) and repair the lesions caused by injury. They send chemical signals that stimulate the growth of nerve cells. They also generate blood vessels that deliver oxygen and nutrients (and clear out toxic substances).

In works of science fiction, you may have read about nanobots. These are theoretical nanomachines that can fix profound biological damage. But the truth is that we all have this type of device in our bodies at the embryonic stage of development. Each uses the complex repair systems that can be found in the human genome.

These are the cells (AST-OPC1) that were given to patients in the SCI trial. The result is that patients who could not breathe on their own can now perform complex physical tasks. We have seen them lift weights, text, and type 35 words a minute and they continue to improve.

Most people assume this therapy must be the most modern of biotechnologies. In truth, its quite old in modern scientific terms. Dr. Michael West oversaw the creation of this therapy over two decades ago as Gerons chief science officer.

When that company stumbled, he brought the clinical trial and Gerons IP into BioTime (*see disclosure below) as Asterias Biotherapeutics. When I spoke to Asterias CEO Steve Cartt, his excitement was palpable. Heres why.

Each year, about 17,000 people experience the kind of spinal cord injuries targeted by the current trial. AST-OPC1 would be the only approved treatment for this condition.

Cartt is now considering plans to extend clinical trials to those who have suffered less serious spinal cord injuries. This means the patient population for AST-OPC1 cells would expand a great deal.

These cells might also be used to treat other neurological diseases. Multiple sclerosis, for example, also involves the deterioration of the myelin nerve sheath. But this is just the tip of iceberg for pluripotent stem cell therapies. Many of our worst diseases can be addressed by these biological nanobots.

If spinal cords can be repaired, so can the connective tissue deterioration that leads to arthritis and joint failures. Im convinced we will see simple injections of stem cells to repair hip, knee, and other joints in the future.

BioTime has also done extensive research into stem cell therapies for heart muscle and cardiovascular repair. In fact, Dr. West has converted some of my cells to embryonic status. He then engineered them to become my heart muscle cells. There have been animal studies as well. The results indicate that these types of cells will repair the damage done by heart attacks.

Next up, though, is blindness. A BioTime subsidiary in Israel, Cell Cure Neurosciences, is in a phase 1/2a trial to treat dry age-related macular degeneration (dry-AMD). Israeli government grants have helped fund this project.

Based on animal trials, it seems that the companys retinal pigment epithelial cells will be successful in treating the leading cause of adult blindness. Dry-AMD is an attractive target because there is no effective treatment. From what Ive learned, I think that these cells will treat the wet form of macular degeneration and other causes of blindness as well.

This is the real importance of the Asterias SCI trial. Right now, were seeing the proof of concept for a biotechnology that will disrupt the entire healthcare market. I've written about this extensively in Tech Digest (subscribe here for free).

This change will happen sooner than you think. Japan has already revised its Pharmaceutical Affairs Act to speed up the approval of stem cell therapies. And on the home front, several of President Trump's candidates for FDA chief have endorsed similar reforms.

(*Disclosure: The editors or principals of Mauldin Economics have a position in BioTime (BTX) which has significant ownership of Asterias stock. They have no plans to sell their position at this time. There is an ethics policy in place that specifies subscribers must receive advance notice should the editors or principals intend to sell.)

This weekly newsletter by biotech expert Patrick Cox highlights research that is much more advanced than most people know, and the profit potential for investors is vast. Read about the latest breakthroughsfrom new, non-invasive cancer treatments to age-reversing nutraceuticals and vaccines that kill any virusas well as the innovative companies that work on them. Get Tech Digest free in your inbox every Monday.

DISCLOSURE: The views and opinions expressed in this article are those of the authors, and do not represent the views of equities.com. Readers should not consider statements made by the author as formal recommendations and should consult their financial advisor before making any investment decisions. To read our full disclosure, please go to: http://www.equities.com/disclaimer

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A Breakthrough in Stem Cell Treatment? - Equities.com

Spinal Cord Stem Cells Comments Off on A Breakthrough in Stem Cell Treatment? – Equities.com | February 18th, 2017

SOUTH SAN FRANCISCO, CA--(Marketwired - February 13, 2017) - VistaGen Therapeutics Inc. (VTGN), a clinical-stage biopharmaceutical company focused on developing new generation medicines for depression and other central nervous system (CNS) disorders, today reported financial results for the third quarter of fiscal 2017 ended December 31, 2016.

The Company also provided a corporate update, including anticipated milestones for AV-101, its new generation, orally available CNS prodrug candidate in Phase 2 development, initially for the adjunctive treatment of major depressive disorder (MDD) in patients with an inadequate response to standard antidepressant therapies approved by the U.S. Food and Drug Administration (FDA).

"We are excited about our progress during the last quarter, with several key advances related to our MDD-focused programs for AV-101, as well as potential regenerative medicine and drug rescue applications of our cardiac stem cell technology. Following productive discussions with the FDA last quarter, our team and key advisors have been working diligently to complete the diverse regulatory and technical activities necessary to support the planned launch of our Phase 2b study of AV-101 next quarter, a study we believe has game-changing potential for the millions of patients who battle MDD every day with inadequate therapies," commented Shawn Singh, Chief Executive Officer of VistaGen. "Also, our recent sublicense agreement with BlueRock Therapeutics was an important advance in our cardiac stem cell program while we remain primarily focused on our Phase 2 programs for AV-101. With potentially catalytic milestones in the coming quarters, we believe we are poised to unlock significant value for our shareholders throughout 2017," added Mr. Singh.

Recent Corporate Highlights:

The U.S. National Institute of Mental Health (NIMH) is currently conducting and fully funding a 20 to 25-patient Phase 2a study of AV-101 as a monotherapy for treatment-resistant MDD under VistaGen's Cooperative Research and Development Agreement (CRADA) with the NIMH (Phase 2a Study). Dr. Carlos Zarate Jr., Chief, Section on the Neurobiology and Treatment of Mood Disorders and Chief of Experimental Therapeutics and Pathophysiology Branch at the NIMH and a leading clinical expert on the use of ketamine for treatment-resistant MDD, is the Principal Investigator of the Phase 2a Study. Following recent guidance from the NIMH, the Company currently anticipates that the NIMH will complete the Phase 2a Study by the end of 2017.

VistaGen is preparing to launch a 280-patient, multi-center, double-blind, placebo controlled Phase 2b efficacy and safety study evaluating AV-101 as a new generation adjunctive treatment for MDD patients with an inadequate response to standard, FDA-approved antidepressant therapies. The Company currently anticipates commencing patient enrollment in the Phase 2b Study in the second quarter of 2017. Dr. Maurizio Fava of Harvard University Medical School will serve as the Principal Investigator of VistaGen's AV-101 Phase 2b Study. Topline clinical results from the Phase 2b Study are currently anticipated by the end of 2018.

Dr. Mark Smith, Chief Medical Officer of VistaGen, commented, "We look forward to starting patient enrollment in our Phase 2b study of AV-101 as an adjunctive therapy in the treatment of MDD. We believe we have significantly de-risked this Phase 2b study with a clinical trial methodology that is designed to overcome the challenge of placebo effects in psychiatric clinical trials. Based on the study protocol we have designed in collaboration with key opinion leaders in depression and neuroscience, including our Principal Investigator, Dr. Fava, we expect that achieving a successful outcome of our Phase 2b study will be integral in realizing AV-101's potential to displace atypical antipsychotics and non-drug interventions in the current depression treatment paradigm, representing a much needed treatment solution for physicians and patients, as well as an enormous opportunity for VistaGen."

Expected Near-Term Milestones:

"The NIMH recently updated us on their timelines for the completion of the Phase 2a study of AV-101 as a monotherapy for MDD. The Phase 2a study protocol requires considerable time and dedication from both the study participants and the multi-disciplinary NIMH teams involved. Patient enrollment for the Phase 2a study remains ongoing and we currently anticipate the NIMH's completion of the study by the end of 2017. Our top priority is to execute our plans for our Phase 2b study of AV-101 as a new generation adjunctive treatment of MDD, and we remain on track to launch that important study in the second quarter. As part of our Phase 2 program, this Phase 2b study has been specifically designed to achieve important outcomes that will be key to advancing AV-101 into a pivotal program in MDD and more broadly beyond MDD, as we continue to advance our global commercialization strategy. We are confident that our Phase 2 program is a major step forward in positioning AV-101 as a potentially transformative adjunctive treatment of MDD and other CNS disorders," concluded Mr. Singh.

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Summary of Financial Results for the Third Quarter of Fiscal 2017 Ended December 31, 2016

Revenue

The Company recognized $1.25 million in sublicense revenue pursuant to its cardiac stem cell technology sublicense agreement with BlueRock Therapeutics, a next generation regenerative medicine company established by Bayer AG and Versant Ventures, in the third fiscal quarter ended December 31, 2016.

Research and Development Expenses

Research and development expense totaled $1.61 million for the third fiscal quarter ended December 31, 2016, compared to $806,300 for the quarter ended December 31, 2015, reflecting increasing focus on nonclinical and clinical development of AV-101 and preparations for launch of the AV-101 Phase 2b Study in the second quarter of 2017.

General and Administrative Expenses

General and administrative expense increased to $2.3 million in the third fiscal quarter ended December 31, 2016, from $1.3 million for the same period in the prior year. The increase in G&A expense is the result of increased noncash stock compensation expense attributable to option and warrant grants in the period to employees, independent members of the Company's Board of Directors and consultants and other noncash expense related to grants of equity securities in payment of certain professional services, and a combination of corporate expenses, including investor relations and corporate development initiatives.

Net Loss

For the third fiscal quarter ended December 31, 2016, the Company reported a net loss of approximately $2.6 million, or a net loss attributable to common stockholders of $0.34 per common share, compared to a net loss of approximately $2.1 million, or a net loss attributable to common stockholders of $1.95 per common share for the same period in the prior year.

Cash and Cash Equivalents

As of December 31, 2016, the Company had approximately $5.6 million of cash, cash equivalents and short term receivables, including a $1.25 million short term sublicense fee receivable from BlueRock Therapeutics pursuant to the Company's December 2016 technology sublicense agreement with BlueRock Therapeutics. In January 2017, the Company received the $1.25 million sublicense fee payment from BlueRock Therapeutics and currently believes it has sufficient financial resources to fund its expected operations at least through the first half of 2017, including preparation for and launch of its planned AV-101 Phase 2b Study in MDD.

About VistaGen

VistaGen Therapeutics, Inc. (VTGN), is a clinical-stage biopharmaceutical company focused on developing new generation medicines for depression and other central nervous system (CNS) disorders. VistaGen's lead CNS product candidate, AV-101, is a new generation oral antidepressant drug candidate in Phase 2 development. AV-101's mechanism of action is fundamentally differentiated from all FDA-approved antidepressants and atypical antipsychotics used adjunctively to treat MDD, with potential to drive a paradigm shift towards a new generation of safer and faster-acting antidepressants. AV-101 is currently being evaluated by the U.S. National Institute of Mental Health (NIMH) in a Phase 2a monotherapy study in MDD being fully funded by the NIMH and conducted by Dr. Carlos Zarate Jr., Chief, Section on the Neurobiology and Treatment of Mood Disorders and Chief of Experimental Therapeutics and Pathophysiology Branch at the NIMH. VistaGen is preparing to launch a 280-patient Phase 2b study of AV-101 as an adjunctive treatment for MDD patients with inadequate response to standard, FDA-approved antidepressant therapies. Dr. Maurizio Fava of Harvard University will be the Principal Investigator of the Phase 2b study. AV-101 may also have the potential to treat multiple CNS disorders and neurodegenerative diseases in addition to MDD, including chronic neuropathic pain, epilepsy, Parkinson's disease and Huntington's disease, where modulation of the NMDAR, AMPA pathway and/or key active metabolites of AV-101 may achieve therapeutic benefit.

VistaStem Therapeutics is VistaGen's wholly owned subsidiary focused on applying human pluripotent stem cell (hPSC) technology, internally and with third-party collaborators, to discover, rescue, develop and commercialize proprietary new chemical entities (NCEs), including small molecule NCEs with regenerative potential, for CNS and other diseases, and cellular therapies involving stem cell-derived blood, cartilage, heart and liver cells. In December 2016, VistaGen exclusively sublicensed to BlueRock Therapeutics LP, a next generation regenerative medicine company established by Bayer AG and Versant Ventures, rights to certain proprietary technologies relating to the production of cardiac stem cells for the treatment of heart disease.

For more information, please visit http://www.vistagen.com and connect with VistaGen on Twitter, LinkedIn and Facebook.

Forward-Looking Statements

The statements in this press release that are not historical facts may constitute forward-looking statements that are based on current expectations and are subject to risks and uncertainties that could cause actual future results to differ materially from those expressed or implied by such statements. Those risks and uncertainties include, but are not limited to, risks related to the successful launch, continuation and results of the NIMH's Phase 2a (monotherapy) and/or the Company's planned Phase 2b (adjunctive therapy) clinical studies of AV-101 in MDD, and other CNS diseases and disorders, protection of its intellectual property, and the availability of substantial additional capital to support its operations, including the development activities described above. These and other risks and uncertainties are identified and described in more detail in VistaGen's filings with the Securities and Exchange Commission (SEC). These filings are available on the SEC's website at http://www.sec.gov. VistaGen undertakes no obligation to publicly update or revise any forward-looking statements.

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VistaGen Therapeutics Reports Fiscal Third Quarter 2017 Financial ... - Yahoo Finance

Cardiac Stem Cells Comments Off on VistaGen Therapeutics Reports Fiscal Third Quarter 2017 Financial … – Yahoo Finance | February 18th, 2017

PTH regulates bone marrow progenitor fate Nature.com New research published in Cell Metabolism reveals an important mechanism underlying the anabolic effects of parathyroid hormone (PTH) on bone. Mice with conditional deletion of the gene encoding the PTH 1 receptor (PTH1R) in bone marrow progenitors ...

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PTH regulates bone marrow progenitor fate - Nature.com

Bone Marrow Stem Cells Comments Off on PTH regulates bone marrow progenitor fate – Nature.com | February 18th, 2017

Adult stem cells collected directly from human fat are more stable than other cells -- such as fibroblasts from the skin -- and have the potential for use in anti-aging treatments, according to researchers from the Perelman School of Medicine at the University of Pennsylvania. They made the discovery after developing a new model to study chronological aging of these cells. They published their findings this month in the journal Stem Cells.

Chronological aging shows the natural life cycle of the cells -- as opposed to cells that have been unnaturally replicated multiple times or otherwise manipulated in a lab. In order to preserve the cells in their natural state, Penn researchers developed a system to collect and store them without manipulating them, making them available for this study. They found stem cells collected directly from human fat -- called adipose-derived stem cells (ASCs) -- can make more proteins than originally thought. This gives them the ability to replicate and maintain their stability, a finding that held true in cells collected from patients of all ages.

"Our study shows these cells are very robust, even when they are collected from older patients," said Ivona Percec, MD, director of Basic Science Research in the Center for Human Appearance and the study's lead author. "It also shows these cells can be potentially used safely in the future, because they require minimal manipulation and maintenance."

Stem cells are currently used in a variety of anti-aging treatments and are commonly collected from a variety of tissues. But Percec's team specifically found ASCs to be more stable than other cells, a finding that can potentially open the door to new therapies for the prevention and treatment of aging-related diseases.

"Unlike other adult human stem cells, the rate at which these ASCs multiply stays consistent with age," Percec said. "That means these cells could be far more stable and helpful as we continue to study natural aging."

ASCs are not currently approved for direct use by the Food and Drug Administration, so more research is needed. Percec said the next step for her team is to study how chromatin is regulated in ASCs. Essentially, they want to know how tightly the DNA is wound around proteins inside these cells and how this affects aging. The more open the chromatin is, the more the traits affected by the genes inside will be expressed. Percec said she hopes to find out how ASCs can maintain an open profile with aging.

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Stem cells collected from fat may have use in anti-aging treatments ... - Science Daily

Skin Stem Cells Comments Off on Stem cells collected from fat may have use in anti-aging treatments … – Science Daily | February 18th, 2017

OSAKA, Japan & LEUVEN, Belgium--(BUSINESS WIRE)--Takeda Pharmaceutical Company Limited (TSE:4502) (Takeda) and TiGenix NV (Euronext Brussels and Nasdaq:TIG) (TiGenix) today announced new data from the Phase 3 ADMIRE-CD clinical trial, which indicated that investigational compound Cx601, a suspension of allogeneic expanded adipose-derived stem cells (eASC), maintained long-term remission of treatment refractory complex perianal fistulas in patients with Crohns disease over 52 weeks.1 Results were presented at the 12th Congress of the European Crohns and Colitis Organisation (ECCO).

The ADMIRE-CD trial is a randomized, double-blind, controlled, Phase 3 trial, designed to investigate the efficacy and safety of the investigational compound Cx601 for the treatment of complex perianal fistulas in patients with Crohns disease.2 Patients were randomized to a single administration of Cx601 cells or placebo (control), both added to standard of care.1 A significantly greater proportion of patients in the Cx601 group versus the control group achieved clinical and radiological combined remission* (56.3% and 38.6%; p=0.010), and clinical remission (59.2% and 41.6%; p=0.013) at week 52 in the modified intention-to-treat population (mITT).1 Of those mITT patients who had shown combined remission at week 24, a greater number in the Cx601 group versus the control group reported no relapse at week 52 (75.0% and 55.9%).1 The rates and types of treatment related adverse events (non-serious and serious) and discontinuations due to adverse events were indicated to be similar in both groups (Cx601: 20.4%; control: 26.5%).1

Crohns disease is a chronic inflammatory disease of the gastrointestinal tract, which is thought to affect up to 1.6 million people in Europe.3 Complex perianal fistulas are a complication for people living with Crohns disease and there are limited treatment options. Recognizing the rare and debilitating nature of the disorder, and lack of treatment options, in 2009 the European Commission granted Cx601 orphan designation for the treatment of anal fistula. In March 2016, TiGenix announced that it submitted the Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for Cx601, and a decision by the EMA is expected in 2017. Additionally, in September 2016 orphan drug status was received from the Swiss Agency for Therapeutic Products (Swissmedic) regarding Cx601 for the rare disease complex perianal fistulas in Crohns disease.4

Perianal fistulizing Crohns disease is difficult to treat with currently available therapies and often leads to pain, swelling, infection and incontinence, said Dr. Asit Parikh, Head of Takedas Gastroenterology Therapeutic Area Unit. Existing therapies are limited and associated with complications and a high failure rate. Cx601 may offer patients an alternative treatment option.

These data highlight that the efficacy and safety of a single administration of Cx601 were maintained during one year of follow up, said Dr. Marie Paule Richard, Chief Medical Officer at TiGenix. It is important to also note that the definition of combined remission used in the ADMIRE-CD study, which includes both clinical and radiological assessment by MRI, is more stringent than the criteria commonly used in previous large scale, randomized clinical trials evaluating perianal fistulas in Crohns disease, based only on clinical assessment.

A global pivotal Phase 3 trial for U.S. registration with Cx601 for the treatment of complex perianal fistulas is expected to be initiated by TiGenix in 2017. In the U.S., TiGenix intends to apply for fast track designation from the U.S. Food and Drug Administration (FDA), which would facilitate and expedite the development and review process in the U.S.

Takedas Commitment to Gastroenterology

Takeda is a global leader in gastroenterology. With expertise spanning more than 25 years, the companys dedication to innovation continues to evolve and have a lasting impact. ENTYVIO (vedolizumab) demonstrates Takedas global capabilities and expansion into the specialty care market in gastroenterology and biologics. Designed and developed specifically to target the gastrointestinal (GI) tract, ENTYVIO was launched in 2014 for the treatment of adults with moderate to severe ulcerative colitis and Crohns disease. TAKECAB (vonoprazan fumarate) is Takeda's potassium-competitive acid blocker and was launched in Japan in 2015. Takeda also markets motility agent AMITIZA (lubiprostone), which originally launched in 2006 for the treatment of chronic idiopathic constipation, and received subsequent approval to treat irritable bowel syndrome with constipation and opioid-induced constipation. Preceding these notable launches, Takeda pioneered gastroenterological breakthroughs in proton pump inhibitors beginning in the 1990s with lansoprazole.Through specialized and strategic in-house development, external partnerships, in-licensing and acquisitions, Takeda currently has a number of promising early stage GI assets in development, and remains committed to delivering innovative, therapeutic options for patients with gastrointestinal and liver diseases.

About Takeda Pharmaceutical Company

Takeda Pharmaceutical Company Limited is a global, R&D-driven pharmaceutical company committed to bringing better health and a brighter future to patients by translating science into life-changing medicines. Takeda focuses its research efforts on oncology, gastroenterology and central nervous system therapeutic areas. It also has specific development programs in specialty cardiovascular diseases as well as late-stage candidates for vaccines. Takeda conducts R&D both internally and with partners to stay at the leading edge of innovation. New innovative products, especially in oncology and gastroenterology, as well as its presence in emerging markets, fuel the growth of Takeda. More than 30,000 Takeda employees are committed to improving quality of life for patients, working with our partners in health care in more than 70 countries. For more information, visit http://www.takeda.com/news.

About TiGenix

TiGenix NV (Euronext Brussels and Nasdaq: TIG) is an advanced biopharmaceutical company focused on developing and commercializing novel therapeutics from its proprietary platforms of allogeneic, or donor-derived, expanded stem cells. Our lead product candidate from the adipose-derived stem cell technology platform is Cx601, which is in registration with the EMA for the treatment of complex perianal fistulas in Crohns disease patients. Our adipose-derived stem cell product candidate Cx611 has completed a Phase I sepsis challenge trial and a Phase I/II trial in rheumatoid arthritis. Effective July 31, 2015, TiGenix acquired Coretherapix, whose lead cellular product candidate, AlloCSC-01, is currently in a Phase II clinical trial in acute myocardial infarction. In addition, the second product candidate from the cardiac stem cell-based platform acquired from Coretherapix, AlloCSC-02, is being developed in a chronic indication. On July 4, 2016, TiGenix entered into a licensing agreement with Takeda, a large pharmaceutical company active in gastroenterology, under which Takeda acquired the exclusive right to develop and commercialize Cx601 for complex perianal fistulas outside the United States. TiGenix is headquartered in Leuven (Belgium) and has operations in Madrid (Spain).

About Cx601

Cx601 is a suspension of allogeneic expanded adipose-derived stem cells (eASC) locally injected. Cx601 is an investigational compound being developed in Crohns disease for the treatment of complex perianal fistulas showing inadequate response to at least one conventional or biologic therapy including antibiotics, immunosuppressants, or anti-TNF agents. Crohns disease is a chronic inflammatory disease of the intestine and, as a complication of it, patients can suffer from complex perianal fistulas, for which there is currently no effective treatment. In 2009, the European Commission granted Cx601 orphan designation for the treatment of anal fistulas, recognizing the debilitating nature of the disease and the lack of treatment options. Cx601 has met the primary end-point in the Phase 3 ADMIRE-CD study, a randomized, double-blind, controlled trial run in Europe and Israel and designed to comply with the requirements laid down by the EMA. Madrid Network issued a soft loan to help finance this Phase 3 study, which was funded by the Secretary of State for Research, Development and Innovation (Ministry of Economy and Competitiveness) within the framework of the INNTEGRA plan. In this trial, patients were randomized to a single administration of Cx601 cells or placebo (control), both added to standard of care. The studys primary endpoint was combined remission, defined as clinical assessment at week 24 of closure of all treated external openings draining at baseline despite gentle finger compression, and absence of collections >2cm confirmed by MRI. In the ITT population (n=212), Cx601 achieved statistically significant superiority (p=0.024) on the primary endpoint with 50% combined remission at week 24 compared to 34% in the control arm. Efficacy results were robust and consistent across all statistical populations. Treatment emergent adverse events (non-serious and serious) and discontinuations due to adverse events were comparable between Cx601 and control arms. The 24-week results have been published by The Lancet, one of the most highly regarded and well known medical journals in the world. The Phase 3 study has completed a follow-up analysis at 52 weeks confirming its sustained efficacy and safety profile. Top line follow-up data showed that in the ITT population Cx601 achieved statistical superiority (p=0.012) with 54% combined remission at week 52 compared to 37% in the control arm. Long-term results also showed that, of patients with combined remission at week 24, a higher proportion of patients treated with Cx601 had no relapse at week 52 (75.0% vs. 55.9%). Based on the positive 24-weeks Phase 3 study results, TiGenix has submitted a Marketing Authorization Application to the EMA in early 2016. TiGenix is preparing to develop Cx601 in the U.S. after having reached an agreement with the FDA through a special protocol assessment procedure (SPA) in 2015. On July 4, 2016, TiGenix entered into a licensing agreement with Takeda, a pharmaceutical company leader in gastroenterology, whereby Takeda acquired an exclusive right to develop and commercialize Cx601 for complex perianal fistulas in Crohns patients outside of the U.S.

-Ends-

____________

* defined as clinical assessment of closure of all treated external openings draining at baseline, despite gentle finger compression, and absence of collections >2cm confirmed by MRI

References

1 Pans, J, Garca-Olmo, D, Van Assche, G, et al., Long-term efficacy and safety of Cx601, allogeneic expanded adipose-derived mesenchymal stem cells, for complex perianal fistulas in Crohns Disease: 52-week results of a phase III randomized controlled trial. ECCO 2017; Barcelona: Abstract OP009.

2 Clinicaltrials.gov. Adipose Derived Mesenchymal Stem Cells for Induction of Remission in Perianal Fistulizing Crohn's Disease (ADMIRE-CD). https://clinicaltrials.gov/ct2/show/NCT01541579?term=cx601&rank=2. Published February 2012. Accessed February 9, 2017.

3 Burisch, J, Jess, T, Martinato, M, et al., on behalf of ECCO EpiCom. The burden of inflammatory bowel disease in Europe. J Crohns Colitis. 2013; 7: 322-337.

4 Swissmedic. About us Collaboration National collaboration Patients and Users. Available at https://www.swissmedic.ch/ueber/01398/01400/03296/index.html?lang=en. Accessed February 9, 2017.

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Takeda and TiGenix Report New Data Highlighting Maintenance of ... - Business Wire (press release)

Cardiac Stem Cells Comments Off on Takeda and TiGenix Report New Data Highlighting Maintenance of … – Business Wire (press release) | February 17th, 2017

As a boy growing up in Nigeria, Abba Zubair dreamed of becoming an astronaut.

But as he prepared to apply to college, an advisor told him to find a different path.

He said it may be a long time before Nigeria sends rockets and astronauts into space, so I should consider something more practical, Zubair saud.

He decided to become a physician, and is currently the medical and scientific director of the Cell Therapy Laboratory at the Mayo Clinic in Jacksonville. And while hell almost certainly never get to make a journey outside the Earths atmosphere himself, if the weather stays good Saturday hell be sending a payload into space.

A SpaceX Falcon 9 rocket is scheduled to launch at 10:01 a.m. Saturday from the Kennedy Space Center on a cargo delivery mission to the International Space Station. Among the cargo it will be carrying are several samples of donated adult stem cells from Zubairs research lab.

Zubair believes adult stem cells, extracted from bone marrow, are the future of regenerative medicine. Currently at the Mayo Clinic in Jacksonville they are being used in clinical trials to treat knee injuries and transplanted lungs.

But a big problem with using stem cells to treat illnesses is that it may require up to 200 million cells to treat a human being and the cells take a long time to reproduce. Based on studies using simulators on Earth, Zubair believes that the stem cells will more quickly mass produce in microgravity.

Thats the hypothesis hell be testing as the stem cells from his lab spend a month aboard the space station. Astronauts will conduct experiments measuring changes in the cells. They will then be returned on an unmanned rocket and Zubair will continue to study them in his lab.

We want to undersrand the process by which stem cells divide so we can grow them at a faster rate and also so we can suppress them when treating cancer, he said.

Zubair became interested in the idea of sending stem cells into space four years ago, when he learned of a request for proposals that involved medicine and outer space. Hes been trying to arrange to send stem cells into space for three years.

In May 2015, he sent stem cells to the edge of space as a hot-air balloon carried a capsule filled with cells from his lab to about 100,000 feet then dropped the capsule. The idea was to test how the cells handled re-entry into the Earths atmosphere.

It turned out well, he said. The cells were alive and functioning.

Zubair was supported in that effort as he is being supported in sending cells to the space station by the Center for Applied Science Technology. Its chief executive is Lee Harvey, a retired Navy pilot and former astronaut candidate who lives in Orange Park.

While stem cells have myriad potential medical applications, one that particularly interests Zubair is the use of them in treating stroke patients. Its a personal cause to Zubair, whose mother died of a stroke in 1997.

Weve shown that an infusion of stem cells at the site of stroke improves the inflammation and also secretes factors for the regeneration of neurons and blood vessels, he said.

Zubair hasnt entirely given up on his old dream of being an astronaut. Hes applied for the civilian astronaut program. But he doesnt expect that to happen.

Im not sure I made a cut, he said. I just wanted to apply.

And he realizes what a long, strange trip hes made.

I have come so far from Africa to here, he said, and now Im sending stem cells into space.

Charlie Patton: (904) 359-4413

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Mayo researcher Abba Zubair is sending stem cells for study on the International Space Station - Florida Times-Union

Bone Marrow Stem Cells Comments Off on Mayo researcher Abba Zubair is sending stem cells for study on the International Space Station – Florida Times-Union | February 17th, 2017

Stem cell therapy treatment gives new lease of life to 5-year-old Jamshedpur February 17, 2017 , by Desk 1

Ranchi : Till very recently, it was believed that brain damage is irreversible. However, now with emerging research; we understand that it is possible to repair the damaged brain tissue using cell therapy.

Again, today there are still many people in India who have not preserved their stem cells through cord blood banks. For all those patients, who have lost their hopes in finding a new treatment for neurological related disorders, adult stem cell therapy offers a new hope for such kind of patients.

Dr Alok Sharma, Director, NeuroGen Brain and Spine Institute, Professor and Head of Neurosurgery, LTMG Hospital & LTM Medical College, Sion said Stem cell therapy is emerging as one of the newer treatment options for conditions like Autism, Cerebral Palsy, Mental retardation, Muscular Dytrophy, Spinal Cord Injury, Paralysis, Brain Stroke, Cerebellar Ataxia and Other Neurological Disorders. This treatment has the potential to repair the damaged neural tissue at molecular, structural and functional level.

Dr. NandiniGokulchandran, Deputy Director, Neurogen Brain and Spine Institute saidStem Cell Therapy (SCT) done at NeuroGen Brain and Spine Institute is a very simple and safe procedure. Stem Cells are taken from patients own bone marrow with the help of one needle and are injected back in their Spinal Fluid after processing.

Since they are taken from the patients own body there is no rejection, no side effects, hence making SCT a completely safe procedure.

Today, we are presenting a case study of Ranchi based 5 yrs old Master Dhairya Singh. He is a known case of brain damage due to lack of oxygen but not during birth. Dhairya was born in a normal manner, cried immediately after birth also his birth weight was appropriate.

There were no immediate post-natal complications reported. Dhariya was a normal child till the age of one and half years old. Then one day he suffered from an episode of pneumonia for which he was hospitalized for 6 days.

Last updated:Friday, February 17, 2017

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Stem cell therapy treatment gives new lease of life to 5-year-old - Avenue Mail

Spinal Cord Stem Cells Comments Off on Stem cell therapy treatment gives new lease of life to 5-year-old – Avenue Mail | February 16th, 2017

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Zc]>!we >'q6s>n@0aS~!I1Y6vV7J``4G$SGKjt?~ZEbvLWp"xETq [ ky/xH4iUB!X8L[q,5Z'cPL,>qKGV,cd72g]Xsn.Vh7%:6cwf,Y7njiF(E7: ssmY%XX.Ts>>v'p~@u]5b^; D(b{leDv M9:zT6R^3mk$^biv& \_%0L&.0Vd=Y,@=@=^vC!W!8Dy>E7_u_uAyy6xzGv[}{HkuTX$ I4nhlWtEt( Zhh]Ko8+[HS,NzHO INlnEI8EbH|C1MKoij[8iN]/]VMI~_pF8Y(nZhmp6R9/Kz^scV}tLj;3q/U="Ye?y%z%/yV)R*p7o[]ZU(YIohCiiwY6O2LAB]H+>o(4*d|+He_Wog6!Wu) mohEmB3NXlZI{J_E $xISAE/Rh43R$v!jmV R..k2naN4.b+zw6IrZ=HL.#>4K]RFxQ0|SPO#R.;'-T~w0/3i3+zJ/ls3}d<4V2{^{HO^F{mSvZN(A?tMpFuL}e-%rNy0X~!nIY6#^Z|l/%?nNphNzu0I /4%]Ko@+HJ%J>UzSO#I7`vJm!3qgg}Uwwk[Yx]eS_],J?F!>Pjh.Zv|qzj#%U-VZk0E5o^ksDc?5OF%fGT@bk5+6w.TsE78`-Mra&m`{aB$LJcsWejL{.-s* ROiNsZg_K`}>fXp/IP$+v%dJ+2n g:)1F8xf'7hE8, -F=yF :[LMDM.( 80O+|D3WBa" ) J6AL#ZP]T#K9$44W #^HjKz~`Ii]77-Ue>A~7^NAs}^lwD-lZfS-XU,SO'U+2>O7v6:4Z]u{5K;UzH; in+S9`x9N" u l`x4M]t 4jk}Oe5HY%LeDV-[#R{v[M]) jD% wQ0o-w(7e#6"^NX%8

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Hello, again, Dolly - The Economist

IPS Cell Therapy Comments Off on Hello, again, Dolly – The Economist | February 16th, 2017

Science Daily

Your brain's got rhythm: Synthetic brain mimics Science Daily Salk scientists create synthetic brain systems called 'circuitoids' to better understand dysfunctional movements in Parkinson's, ALS and other diseases. Confocal microscope immunofluorescent image of a spinal cord neural circuit made entirely from stem ... and more »

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Your brain's got rhythm: Synthetic brain mimics - Science Daily

Spinal Cord Stem Cells Comments Off on Your brain’s got rhythm: Synthetic brain mimics – Science Daily | February 15th, 2017

Back to Browse Journals Journal of Neurorestoratology Volume 5

Zhijian Cheng, Xijing He

Department of Orthopedics, The Second Affiliated Hospital of Xian Jiaotong University, Xian, Shaanxi, Peoples Republic of China

Abstract: Spinal cord injury (SCI) is a traumatic event that involves not just an acute physical injury but also inflammation-driven secondary injury. Macrophages play a very important role in secondary injury. The effects of macrophages on tissue damage and repair after SCI are related to macrophage polarization. Stem cell transplantation has been studied as a promising treatment for SCI. Recently, increasing evidence shows that stem cells, including mesenchymal stem, neural stem/progenitor, and embryonic stem cells, have an anti-inflammatory capacity and promote functional recovery after SCI by inducing macrophages M1/M2 phenotype transformation. In this review, we will discuss the role of stem cells on macrophage polarization and its role in stem cell-based therapies for SCI.

Keywords: stem cells, macrophages, spinal cord injury, polarization

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Anti-inflammatory effect of stem cells against spinal cord injury via | JN - Dove Medical Press

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Belleville News-Democrat

A baby's first act, saving a life Belleville News-Democrat Currently, stem cells are being researched to try to find cures or ways to treat autism, spinal cord injury, stroke recovery and Alzheimer's disease. Doll-Pollard said that it is incredibly important for the family to weigh these options before a ...

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A baby's first act, saving a life - Belleville News-Democrat

Spinal Cord Stem Cells Comments Off on A baby’s first act, saving a life – Belleville News-Democrat | February 15th, 2017

February 15, 2017 A single human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM). Cells such as these were used to assess tyrosine kinase inhibitors for cardiotoxicity in a high-throughput fashion. Credit: Dr. Arun Sharma at Dr. Joseph Wus laboratory at Stanford University

Researchers at the Stanford University School of Medicine used heart muscle cells made from stem cells to rank commonly used chemotherapy drugs based on their likelihood of causing lasting heart damage in patients.

Drugs known as tyrosine kinase inhibitors can be an effective treatment for many types of cancers, but they also have severe and sometimes fatal side effects. Using lab-grown heart cells, Stanford researchers were able to assess the drugs' various effects on heart muscle cells, including whether the cells survived, were able to beat rhythmically and effectively, responded appropriately to electrophysiological signals and communicated with one another.

The researchers found that their assay can accurately identify those tyrosine kinase inhibitors already known to be the most dangerous in patients. In the future, they believe their system may prove useful in the early stages of drug development to screen new compounds for cardiotoxicity.

"This type of study represents a critical step forward from the usual process running from initial drug discovery and clinical trials in human patients," said Joseph Wu, MD, PhD, director of the Stanford Cardiovascular Institute and a professor of cardiovascular medicine and of radiology. "It will help pharmaceutical companies better focus their efforts on developing safer drugs, and it will provide patients more effective drugs with fewer side effects."

A paper describing the research will be published Feb. 15 in Science Translational Medicine. Wu, who holds the Simon H. Stertzer Professorship, is the senior author. Former graduate student Arun Sharma, PhD, is the lead author.

'Multiple measurements'

"We used multiple measurements to accurately predict which of the tyrosine kinase inhibitors were the most cardiotoxic," said Sharma. "The drugs with the lowest safety indices in our study were also those identified by the Food and Drug Administration as the most cardiotoxic to patients. Other drugs that are not as cardiotoxic performed much better in our assays."

Validating the researchers' cardiac-safety test on drugs with extensive clinical track records is necessary before the assay can be used to predict with confidence the likely clinical outcomes of drugs still under development.

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Sharma, Wu and their colleagues created heart muscle cells called cardiomyocytes from induced pluripotent stem cells, or iPS cells, from 11 healthy people and two people with kidney cancer. They grew the lab-made cardiomyocytes in a dish and tested the effects of 21 commonly used tyrosine kinase inhibitors on the cells.

They found that treatment with drug levels equivalent to those taken by patients often caused the cells to beat irregularly and begin to die. The cells also displayed differences in the electrophysiological signaling that controls their contraction. The researchers used these and other measurements to develop a cardiac safety index for each drug.

They found that those drugs known to be particularly dangerous to heart function, such as nilotinib, which is approved for the treatment of chronic myelogenous leukemia, and vandetanib, which is approved for the treatment of some types of thyroid cancer, also had the lowest safety indices based on the assay; conversely, those known to be better tolerated by patients ranked higher on their safety index. Prescribing information for both nilotinib and vandetanib contains warnings from the FDA about the drugs' potential cardiotoxicity.

An activity increase in an insulin responsive pathway

Six of the 21 tyrosine kinase inhibitors tested were assigned cardiac safety indices at or below 0.1the threshold limit at which the researchers designated a drug highly cardiotoxic. Three of these six are known to inhibit the same two signaling pathways: VEGFR2 and PDGFR. The researchers noticed that cells treated with these three drugs ramped up the activity of a cellular signaling pathway that responds to insulin or IGF1, an insulinlike growth factor.

This discovery, coupled with the fact that treatment with insulin or IGF1 is known to enhance heart function during adverse cardiac events such as heart attacks, led the researchers to experiment further. They found that exposing the cells to insulin or IGF1 made it less likely they would die due to tyrosine kinase inhibitors blocking the VEGFR2 and PDGFR pathways. Although more research is needed, these findings suggest it may be possible to alleviate some of the heart damage in patients receiving these chemotherapies.

The current study mirrors another by Wu's lab that was published in April 2016 in Nature Medicine. That research focused on the toxic effect of a chemotherapy drug called doxorubicin on iPS cell-derived cardiomyocytes. Doxorubicin, which indiscriminately kills any replicating cells, is increasingly being replaced by more targeted, cancer-specific therapies such as the tyrosine kinase inhibitors tested in the current study.

"The switch from doxorubicin is a result of the paradigm shift in cancer treatment to personalized, precise treatment as emphasized by President Obama's 2015 Precision Medicine Initiative," said Wu. "Moving even further, we're discovering that many tyrosine kinase inhibitors are themselves significantly cardiotoxic, and some have been withdrawn from the market. There is a critical need for a way to 'safety test' all drugs earlier in development before they are administered to patients. Our drug safety index is a step in that direction."

Explore further: Stem cell-based screening methods may predict heart-related side effects of drugs

More information: "High-throughput screening of tyrosine kinase inhibitor cardiotoxicity with human induced pluripotent stem cells," Science Translational Medicine, stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.aaf2584

Coaxing stem cells from patients to become heart cells may help clinicians personalize drug treatments and prevent heart-related toxicity.

Heart muscle cells made from induced pluripotent stem cells faithfully mirror the expression patterns of key genes in the donor's native heart tissue, according to researchers at the Stanford University School of Medicine. ...

Researchers at Moffitt Cancer Center have determined that chronic myeloid leukemia patients who are treated with a class of oral chemotherapy drugs known as a tyrosine kinase inhibitors have significant side effects and quality-of-life ...

Some cancers can be effectively treated with drugs inhibiting proteins known as receptor tyrosine kinases, but not those cancers caused by mutations in the KRAS gene. A team of researchers led by Jeffrey Engelman, at Massachusetts ...

Acute myeloid leukemia (AML) is a cancer of myeloid stem cells that develops in both adult and pediatric populations. Mutations that cause hyperactivation of the FMS-like tyrosine kinase 3 (FLT3) are commonly found in AML, ...

Fat cells are not simply big blobs of lipid quietly standingby in the bodyinstead, they send out hormones and other signaling proteins that affect many types of tissues. Scientists at Joslin Diabetes Center now have identified ...

Researchers at the Stanford University School of Medicine used heart muscle cells made from stem cells to rank commonly used chemotherapy drugs based on their likelihood of causing lasting heart damage in patients.

Research published today in Nature from scientists at Huntsman Cancer Institute (HCI) at the University of Utah shows how epithelial cells naturally turn over, maintaining constant numbers between cell division and cell death.

Scientists are working to understand the mechanisms that make weight loss so complicated. Exercise burns calories, of course, but scientists are also looking at how the body burns more energy to stay warm in cold temperatures.

Biologists have known for decades that enduring a short period of mild stress makes simple organisms and human cells better able to survive additional stress later in life. Now, scientists at Sanford Burnham Prebys Medical ...

A puzzling question has lurked behind SMA (spinal muscular atrophy), the leading genetic cause of death in infants.

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Scientists create scorecard index for heart-damaging chemo drugs - Medical Xpress

Cardiac Stem Cells Comments Off on Scientists create scorecard index for heart-damaging chemo drugs – Medical Xpress | February 15th, 2017

Seventy-year-old Peggy Agar has known since she was in her 40s that she and her 12 siblings might be at risk for familial cardiomyopathy, a genetic form of heart disease.

Her mother was diagnosed with it in 1987, and several of her brothers were also subsequently diagnosed with cardiomyopathy.

Given our family history, our family knew we had to be vigilant to keep our hearts as strong as possible, says Agar, who lives in Bloomfield.

But now thanks to the power of genetic testing at UConn Healths Pat and Jim Calhoun Cardiology Center, Agar and her family can determine which family members may be at risk.

Through a routine blood sample, Agars gene sequences were analyzed by Dr. Travis Hinson, a cardiovascular physician-scientist who is a new faculty member with a joint appointment at UConn Health and the Jackson Laboratory for Genomic Medicine.

Hinsons advanced genetic analysis revealed that Agar carries a gene mutation that causes dilated cardiomyopathy, a disease of the heart muscle that potentially leads to an enlarged, weakened heart and ultimately heart failure. He identified that Agar carries a mutation in the largest gene in the body called titin that leads to dilated cardiomyopathy in about 1 in 5 patients with a positive family history. In 2015, his laboratory published these findings in the journal Science, where he studied miniature beating human heart tissues engineered from stem cells from patients with conditions similar to Agars.

Hinson says knowing their genetic predisposition allows patients and families to understand why heart disease may continue to be prevalent generation after generation in their family.

If you carry the cardiomyopathy gene, you have a 50 percent chance of passing it to your offspring, says Hinson. Now with the power of genetic testing, we can tell each family member definitely early in their life whether they carry the cardiomyopathy genetic mutation, and intervene early to try to prevent any symptoms of the disease before they occur.

Agar says the genetic test results will arm her familys younger and future generations with important knowledge.

Now our family can better safeguard ourselves and younger generations at an early age to take extra precautions when it comes to our heart health, she says. Because of the way this myopathy develops in our family, we have learned that it is very important when we seek medical care that the physicians we see are aware of this family history.

Another positive aspect of the testing is that family members who are found not to have the gene no longer need to worry about passing the gene on to their children.

Agar has received comprehensive treatment from a team of physicians at UConn Healths Calhoun Cardiology Center, including cardiologist Dr. Jason Ryan and electrophysiologist Dr. Christopher Pickett. Since she was first diagnosed with cardiomyopathy in 2009, she has been treated for its complications. These include atrial fibrillation, the most common form of arrhythmia, and ventricular tachycardia, life-threatening and chaotic heart beats that can cause premature or sudden death. To protect her heart against dangerous arrhythmias, Agar takes daily medication; has received cardioversions (which convert an arrhythmia to a normal rhythm) and an ablation procedure (the destruction of tinyparts of heart tissue with radio frequency waves that are triggering arrhythmia); and has an implantable cardio-defibrillator.

As a result of the personalized team approach among the cardiologists who care for her at the Calhoun Cardiology Center, Agars heart function has been nearly normalized. She is grateful to the entire team.

Ive been fortunate, she says. UConns cardiac health team and their staff have been very supportive. They are truly experts in their field and treat me in a very professional and personal manner. They welcome questions and listen to my concerns. They convey the feeling that they truly care about my well-being.

Cardiomyopathy is the most common cause of heart failure. While it can be a genetic condition, it can also be caused by a heart attack or unhealthy lifestyle.

Agar advises others who may have a recurring theme of heart trouble in their family to seek care and not ignore it. With appropriate treatment, she says, cardiac problems dont necessarily have to significantly impact your quality of life. Remember that you are in charge of your own health. Pay attention to the advice of your health care professionals and do those things that are necessary for good health.

To learn more about the Calhoun Cardiology Center at UConn Health, visit: health.uconn.edu/cardiology.

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Cardiovascular Genetic Testing Empowers Patient, Family - UConn Today

Cardiac Stem Cells Comments Off on Cardiovascular Genetic Testing Empowers Patient, Family – UConn Today | February 15th, 2017

Wyoming resident and pediatric nurse Elizabeth Groter has partnered with DKMS (Dynamic Kernel Module Support), the nonprofit leading the fight against blood cancer, to host a bone marrow registration drive in Toulon Friday. The event will be held from 3 to 7 p.m. at the Stark County High School cafeteria, and will help register potential lifesaving donors. Anyone in good general health who is between 18 and 55 can register. The process involves filling out a simple form, understanding the donation methods and swabbing the inside of each cheek for 30 seconds. There is no charge to register. Donations help DKMS cover the $65 registration processing fee but are not required. Groter is a pediatric nurse at Childrens Hospital of Illinois, and a DKMS representative. She was inspired to host a drive with DKMS after experiencing first-hand how simple it is to be added to the KDMS bone marrow registry. With her job experience, Groter has met countless children battling leukemia and other blood cancers who are in need of bone marrow transplants, and wanted to make a difference by helping to grow the registry to find lifesaving matches for patients. Groters uncle is a leukemia survivor and another source of her inspiration. Becoming a part of the bone marrow registry to be a possible match for someone with blood cancer is so incredibly easy, and Im going to make it even easier for you. By doing something as simple as this, you could possibly change someones life in an instant, said Groter. According to DKMS, 70 percent of people suffering from blood-related illnesses must rely on donors outside their families to save their life. Swabbing your cheek is all it takes to register as a potential donor. Anyone who wishes to register as a potential donor but is unable to attend Fridays drive can register online at http://www.dkms.org. DKMS is an international nonprofit organization dedicated to eradicating blood cancers like leukemia and other blood-related illnesses. The organization inspires men and woman around to the world to register as bone marrow and blood stem cell donors.

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Nurse asking people to sign up as bone-marrow donors - Kewanee Star Courier

Bone Marrow Stem Cells Comments Off on Nurse asking people to sign up as bone-marrow donors – Kewanee Star Courier | February 15th, 2017

Human stem cells grown on Kyoto University's "fiber-on-fiber" culturing system(Credit: Kyoto University)

Mighty promising as they are, stem cells certainly aren't easy to come by. Recent scientific advances have however given their production a much-needed boost, with a Nobel-prize winning technology that turns skin cells into embryonic-like stem cells and another that promises salamander-like regenerative abilities being just a couple of examples. The latest breakthrough in the area comes from Japanese researchers who have developed a nanofiber matrix for culturing human stem cells, that they claim improves on current techniques.

The work focuses on human pluripotent stem cells (hPSCs), which have the ability to mature into any type of adult cell, be they those of the eyes, lungs or hair follicles. But that's assuming they can be taken up successfully by the host. Working to improve the odds on this front, scientists have been exploring ways of culturing pluripotent stem cells in a way that mimics the physiological conditions of the human body, allowing them to grow in three dimensions rather than in two dimensions, as they would in a petrie dish.

Among this group is a team from Japan's Kyoto University, which has developed a 3D culturing system it says outperforms the current technologies that can only produce low quantities of low-quality stem cells. The system consists of gelatin nanofibers on a synthetic mesh made from biodegradable polyglycolic acid, resulting in what the researchers describe as a "fiber-on-fiber" (FF) matrix.

The team found that seeding human embryonic stem cells onto this type of matrix saw them adhere well, and enabled an easy exchange of growth factors and supplements. This led to what the researchers describe as robust growth, with more than 95 percent of the cells growing and forming colonies after just four days of culture.

And by designing a special gas-permeable cell culture bag, the team also demonstrated how they could scale up the approach. This is because several of the cell-loaded matrices can be folded up and placed inside the bag, with testing showing that this approach yielded larger again numbers of cells. What's more, the FF matrix could even prove useful in culturing other cell types.

"Our method offers an efficient way to expand hPSCs of high quality within a shorter term," the team writes in its research paper. "Additionally, as nanofiber matrices are advantageous for culturing other adherent cells, including hPSC-derived differentiated cells, FF matrix might be applicable to the large-scale production of differentiated functional cells for various applications."

The research was published in the journal Biomaterials.

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Nanofiber matrix sends stem cells sprawling in all directions - Gizmag - New Atlas

Skin Stem Cells Comments Off on Nanofiber matrix sends stem cells sprawling in all directions – Gizmag – New Atlas | February 15th, 2017