Advanced tissue regeneration treatments fororthopaedic injuries and ailments

From ponies to racehorses, stem cell therapy is becoming an increasingly common treatment for many equine injuries and ailments and is fast becoming the gold standard treatment for canine osteoarthritis. Autologous MSCs (mesenchymal stem cells) for use in the treatment are extracted from a sample of the patients bone marrow or adipose tissue. In horses this is done under standing sedation and local anaesthesia, for dogs a general anaesthetic is required.

The sample is sent to Nupsalas laboratory partner where the stem cells are extracted and cultured - a process that takes around 14 days for canine cells and 21 days for equine. The cultured cells are returned to the veterinary surgeon for ultrasound guided implantation directly into the injury. A faster service is also available for canine stromal vascular fraction (SVF) treatments which are produced by preparing the cellular fraction from canine adipose tissue and returned to the vet within 48 hours.

The patient then undergoes a carefully controlled rehabilitation programme which takes approximately one year for horses and six months for dogs. This encourages a return to full fitness and, in the case of horses, full work or competition. Nupsala offers training to vets using this stem cell therapy for the first time, either on a one to one basis or group CPD training.

Stem cell therapy has been used to treat equine tendons, ligaments1&2 and joints (mainly stifle, some carpus, tarsus, distal DP, subchondral bone cysts, meniscal tears, fetlock problems, synovitis and early stage osteoarthritis). In recent years stem cells have started to be used very sucessfully for treating canine osteoarthritis3.

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Nupsala Stem Cells Therapy - Nupsala Veterinary Services

Doctors are finding new ways to treat multiple myeloma, a blood cancer that attacks cells in your bone marrow. The FDA approved three new drugs in 2015, and more are in the pipeline.

"The improvements are amazing," says Brion Randolph, MD, hematologist and chief of medical oncology at the Cancer Treatment Centers of America in Newnan, GA.

"I've already had a few patients I would've had to tell there were no options," he says. Now he says, the new meds are able to extend lives.

Until recently, doctors usually suggested chemotherapy drugs, which kill cancer cells but can also damage normal cells. The treatment has side effects, like fatigue and nausea. The goal is to put you in "remission" -- remove visible signs of the disease in your body.

In the 1990s and early 2000s, some promising new drugs appeared, including bortezomib (Velcade), lenalidomide (Revlimid), and thalidomide (Thalomid). They help prevent cancer cells from dividing out of control.

Doctors use combos of these drugs, sometimes adding in steroids, to help add years to the lives of people with multiple myeloma.

Treatment has changed in a big way with the arrival of new drugs that target the disease much more precisely. They're designed for people whose disease has returned or who haven't been able to get better with other treatments.

Daratumumab (Darzalex). You may hear your doctor call this a "monoclonal antibody." It puts the immune system -- your body's defense against germs -- to work in fighting multiple myeloma. It helps your body identify and attack cancer cells.

Elotuzumab (Empliciti). It's a drug that also uses your body's immune system to destroy multiple myeloma cells.

Ixazomib (Ninlaro). It's a type of drug called a "proteasome inhibitor." It interferes with the cancer cells' ability to grow and thrive inside your body. It comes with a built-in bonus: You don't need to a visit a clinic to get hooked up to an infusion machine. It's a once-a-week pill that you take at home.

Researchers are studying scores of new treatments that could be available down the road. Some especially encouraging possibilities:

Gene therapy. Researchers hope they'll be able to genetically tweak your body's immune cells to recognize and destroy multiple myeloma.

Gene expression profiling. It's a test that checks which genes are active in your cancer cells. Researchers are trying find a way to use it to figure out if -- and when -- you may need chemotherapy to treat your multiple myeloma.

Personalized drug screening. The idea is to quickly and accurately predict which treatments will be best for you. Researchers at Washington University in St. Louis, for example, are developing imaging procedures that will give you a personal treatment plan.

New drugs. Researchers are working to develop a medicine that blocks interleukin, a chemical that's made by the cells in your bone marrow -- the spongy tissue inside your bones that make blood cells. Interleukin helps multiple myeloma cells to grow.

Researches are also testing new combos of drugs already available to treat the disease. Sometimes the chemotherapy meds you take stop working. Doctors are checking to see if combining medicines will give you new treatment options.

Arsenic trioxide. Doctors already use this chemical to treat some kinds of leukemia, and researchers want to find out if it's helpful for multiple myeloma, too.

New techniques in stem cell transplant. It's an operation that replaces cells in your bone marrow with new ones that make healthy blood cells. To treat multiple myeloma, doctors today mostly use a method that uses your own stem cells for the procedure. But researchers are checking to see if using a donor's stem cells can also help.

There's a lot of research still needed, but doctors are optimistic about the path forward. "More and more effective therapies are constantly being developed," Randolph says. "For multiple myeloma, the future is very hopeful."

SOURCES:

Brion Randolph, MD, hematologist and chief of medical oncology, Cancer Treatment Centers of America, Newnan, GA.

Rapoport, A.P. Nature Medicine, Aug. 21, 2015.

American Cancer Society, "What's New in Multiple Myeloma Research and Treatment?" "How is multiple myeloma treated?"

News release, Washington University School of Medicine, St. Louis.

American Society of Clinical Oncology: "Multiple Myeloma -- Latest Research," "Treatment Options."

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New Multiple Myeloma Treatment: Drugs, Gene Therapy, Stem ...

OUR TECHNOLOGIES

The application of adipose stem cells as a therapeutic product is the result of years of research and development. In recent years, adipose stem cells (ASCs) have gained notoriety since its initial discovery in 2001 (1). Since then, the ASC has become the most popular adult stem cells due to its ease of harvest and ACSs ability to differentiate into multiple lineages (2).

VetCell Therapeutics (VCT) has studied the use of adipose tissue in regenerative medicine and has published manuscripts on the topic. Most of the early work was focused on mouse adipose stem cells and the findings are being applied for use in veterinarian medicine.

A large area of need in veterinary medicine is the treatment of osteoarthritis, which is common in animals as they age. Routine treatment of this ailment is with anti-inflammatory drugs or with surgical procedures. Currently, homologous ACSs are being heavily studied to determine if these cells are able to treat osteoarthritis (3). The results from these studies have been promising and shows a great potential to use these cells for a wide array of ailments.

Two of VCTs publications highlight the use of a subpopulation of ASCs which were derived from animal and human sources. These cells were isolated, expanded and differentiated into osteogenic, chondrogenic and adipogenic lineages. These cells were also placed into a wound healing model and showed improved healing abilities of the skins dermal layers. These cells were also used in a project with a bone scaffolding unit. In an animal model, the transplanted cells mixed with the bone scaffold material differentiated into chondrogenic type cells and started to develop into mature chondrocytes.Currently, VCT is working on projects aimed at using adipose tissue as a source material to treat osteoarthritis. Our data, along with other publications (4), suggest that adipose tissue may be a reliable source for cells that can be used to treat bone and cartilage conditions as well as other indications (5, 6). The need for an efficient treatment is desired for pets diagnosed with arthritis or other osteogenic conditions.

The scientific R&D projects are led by a veterinarian scientist, whom is well respected in the industry and with an impressive publication history. Also part of the team is a consulting veterinarian with a background in stem cell research who focuses on generating clinical treatments with these cells. The team is a group of research specialists who all have training in basic research, with a focus on regenerative medicine. The goal is to strive for highly effective products that are backed by research geared towards improving the lives of our beloved companions.Intellectual Property

VetCell Therapeutics has a number of patents issued in the United States, Asia, Europe, and Australia. The company also has a number of filed patents focused on innovative use of stem cells in regenerative medicine. One of the many goals has been to develop intellectual property to protect the concepts of cell-based therapies and to strengthen the ability for success with cell based treatments.

References:1- Zuk P., Zhu M., Mizuno H., et al., Tissue Engineering, vol. 7, no. 2, pp 211228, 20012- Zuk P., ISRN Stem Cells Volume 2013 Article ID 7139593- Guercio A., Di Marco P., Casella S., et al, Cell Biology Int, vol 36, (2), pp 189194, 20124- Lindroos B, Suuronen R, Miettinen S., Stem Cell Rev. Jun 7, (2) pp 269-91, 20115- Lin F., Kidney International vol 82, pp 731733, 20126- Ha S., Ahn S., Kim S., et al., J Biomed Opt. vol 19(5), 2014

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TECHNOLOGY - VetCell Therapeutics

07 Sep 2017

Researchers are gearing up to start clinical trials that test whether replacement dopamine neurons made from human embryonic stem cells or induced pluripotent stem cells can help patients with Parkinsons disease (PD). In the longest preclinical trial with the largest number of monkeys yet, scientists led by Jun Takahashi, Kyoto University, Japan, gave their planned protocol a trial run. Dopamine neurons derived from human iPSCs and implanted into the animals brains improved the monkeys neurological scores and voluntary movements over a year. The findings appeared August 30 inNature.

This may be the most convincing study in a Parkinsonian monkey that pluripotent stem cell-derived dopamine neurons can survive over a long period of time and allow behavioral improvement without forming tumors, said Lorenz Studer, Memorial Sloan Kettering Cancer Center, New York. Because the protocol approximated what Takahashi and others plan to do in humans, it suggests this therapy is almost ready for translation, Studersaid.

In the August 30 Nature Communications, the same researchers also reported a way to minimize the immune response to such grafts. They matched part of the donor and host self signatures, the major histocompatibility complex expressed on cell surfaces. Microglia and infiltrating leukocytes were likelier to turn a blind eye to matched than unmatched dopamine neurons, and more of them survived implantation. The immunosuppressant tacrolimusa.k.a. FK506had the sameeffect.

Neuronal Grafts: Human-derived dopamine neurons thrive in the brain of a monkey model of PD, testing positive for both dopamine transporter (green) and tyrosine hydroxylase (red). [Courtesy of Takahashi et al.,Nature.]

Takahashi plans to start trialing iPSC-derived DA neurons in patients by end of 2018. Dopamine neurons derived from iPSCs or human embryonic stem cells are more readily available than fetal dopaminergic cells, which have seen two decades of trials (Barker et al., 2013). However, iPSC-derived grafts come with safety concerns, not least their tendency to harbor dividing cells that can later form tumors (Trounson 2017; Mar 2017 news). Scientists also debate the value of using a patients own cells versus those from a healthy donor, which may berejected.

In the Nature paper, first author Tetsuhiro Kikuchi and colleagues took fibroblasts or peripheral blood cells from four healthy people and three PD patients and coaxed them to differentiate into midbrain dopamine progenitorcells.

The researchers implanted 28-day-old dopamine progenitor cells bilaterally into the putamen of eight 2-year-old monkeys that had been subjected three months earlier to MPTP, a neurotoxin that wipes out dopaminergic neurons in the substantia nigra. To suppress their immune response, each animal got daily tacrolimus injections from the day before transplantation until the end of the experiment. Three monkeys implanted with vehicle control rather than progenitor cells also received tacrolimus. PET with 11C-PK11195 and (S)-11C-KTP-Me, ligands for activated microglia and inflammation, respectively, registered either no or very mild microglial reaction to the transplants in immunosuppressedanimals.

Over the next 12 months, the researchers assessed neurological symptomsfacial expressions, movement in response to stimuli, tremor, postureand tracked spontaneous movement in 90-minute video recordings taken every quarter. After 12 to 24 months, the researchers sacrificed the animals to see if the cells had integrated into thebrain.

Monkeys that received the cell grafts, regardless of whether the cells came from controls or PD patients, improved their neurological scores by 40 to 50 percent. The control group scores rose by 10 percent. After a year, treated monkeys moved three times as much as they had before transplantation; the controls saw almost no improvement. The researchers detected no signs oftumors.

Based on histological examination, the researchers estimated that the average graft volume was 39 mm3, ranging from 10 to 107 mm3. Roughly 16,000 to 500,000 cellsabout a third of those implantedexpressed the enzyme tyrosine hydroxylase, a marker of dopamine production. According to periodic 18F-DOPA PET scans, dopamine uptake gradually increased over 21 months to about half the level found in normal monkeys. This was true even in monkeys with the smallest grafts, and these animals also showed a treatmentbenefit.

That the graft sizes varied so widely suggests more work needs to be done to select the most successful cell lines for each recipient, said Studer. The researchers report that the most robust grafts expressed the epidermal growth factor Dlk1, and they detected no serotoninergic, GABAergic, cholinergic, or glutamatergic cells among them. Even so, Studer said the high proportion of non-dopamine cells in the transplants need to becharacterized.

Ole Isacson of Harvard University pointed out that the 16,000 cells needed for therapeutic benefit here match the number he found a few years ago in monkeys (Hallett et al., 2015). A major technical achievement that enhances our ability to plan the clinical trials is that the number of surviving cells needed for therapeutic benefit is in the same range, he told Alzforum. The authors conclude that for people, about 100,000 cells would be the minimum needed for a motor effect, according to the paper. That helps FDA determine the reasonable dose, saidIsacson.

On 11C-PK11195 PET scans, monkeys receiving a mismatched cell graft (left) had more activated microglia three months later than animals receiving cells with a matched MHC haplotype (right). [Courtesy of Takahashi et al., NatureCommunications.]

A major concern with grafted cells is the potential for rejection. Implants derived from a patients own cells would be ideal, because they produce no immune response, but the process is lengthy and costly. As reported in the second paper, first author Asuka Morizane investigated a compromiseusing immune compatible grafts. They matched the major histocompatibility complex (MHC) between donor and recipient monkeys to see if that would mitigate graft rejection. MHCs appear on cell surfaces and display proteins from inside the cell to watchful immune cells. They are crucial for those immune cells to distinguish self fromnon-self.

To do this, the authors derived two different iPSC lines from monkeys, turned them into a range of dopamine neural progenitor cells, and injected these cells into the left putamen of 16 monkeys: eight that had at least one identical MHC haplotype, and eight that were mismatched completely. Two animals from each group received the immunosuppressive drug tacrolimus to determine if that helped further. After three months, monkeys receiving the matched grafts did mount an immune response, but it was half as strong as that of monkeys receiving mismatched grafts. MHC matching worked about as well as giving tacrolimus along with the mismatched grafts. At four months, fewer activated microglia and infiltrating leukocytes were seen in the brains of matched monkeys and more dopaminergic neuronssurvived.

The study suggests that MHC matching gives dopamine cells an advantage, though immunosuppressants may still be necessary, wrote Takahashi to Alzforum. He will use MHC-homologous iPSCs in his clinical trial. Banking 50 MHC-characterized iPSC lines would largely cover the Japanese population, though the more heterogeneous populations of the United States and Europe would require hundreds of lines (Nakatsuji et al., 2008; Taylor et al., 2012).

To have an HLA match for every patient is feasible, but requires steep cost and effort and doesnt work perfectly, said Studer. He took from the paper that tacrolimus suppresses the immune system well. For his part, Studer is planning a trial without MHC matching, developing one line of dopaminergic neurons and giving them to all patients along with immunosuppressants. Since matching still causes a minor immune response that would need to be suppressed anyway, he advocates for this cheaperapproach.

Isacson took a different stance. Any immune reaction or requirement for immune suppression could stress an aged persons system, he said. Since MHC matching doesnt get rid of inflammation altogether, he saw it as evidence that iPSCs derived from a patients own cells will work best. They would require no immune suppression. Isacson acknowledged that deriving dopaminergic neurons from donor cells is expensive and hard to industrialize, but expects the cost will fall as the technology develops.Gwyneth DickeyZakaib

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Stem Cells Rescue Movement in Monkey Model of Parkinson's - Alzforum

Tommy, our beloved 8-year-old border collie mix, was diagnosed by MRI with an inoperable tumor on his spinal cord. We had difficulty diagnosing what appeared to be a weak leg, and he began to cry out occasionally as he climbed stairs. We escalated, and our vet referred us to an MRI immediately.

After the diagnosis, the vet specialist said that Tommy was quite stoic because he did not cry out more often, given the location of the tumor. We knew he was not himself, but what we did not know was the level of pain that he lived with that last month of his life.

I question the motivation of these people: How on Earth (in their own words) "during four weeks of screaming in pain" did they not decide that perhaps it was time to let Chuckie go? Who knows what pain he endures now? I was saddened to see that their own motivations have overtaken their empathy for what might be in the best interest of Chuckie.M.J., Manchester, Mo.

Dear Dr. Fox: I was dismayed by the excessive treatment the letter-writer has gotten and is getting for a paraplegic dog. I love animals, have taken good care of my pets and have volunteered and donated to the Missouri Humane Society, so it isn't that I'm anti-animal, but I think what the writer has done for this one dog is too much.

Just think of the hundreds and hundreds of dogs in shelters and the care some of the healthier ones could get if the writer stopped at sensible treatment for that one dog. Actually, that dog is getting better and more extensive care than some children. Enough is enough in trying to help a pet.R.B., Kirkwood, Mo.

Dear M.J. and R.B.: The money that caring people sometimes put out for their beloved animal companions, especially with advances in cancer treatments and stem cell therapies, can be very considerable. Are they being selfish? What then of their love and concern?

Some do choose instead to opt for euthanasia, especially when there is a low chance of recovery, and give a large donation in their animal's name to their local animal shelter or rescue organization.

We cannot compare the quality of medical care and what might be spent on a child in a poor village with a toy poodle in New York City suffering from comparable conditions, nor their chances of recovery. Such situational ethics are confounded by other social and family priorities, availability of services and where there is choice, just how much one feels like spending and can afford in the hope that the loved one will recover. It is a tragedy of the times that here in America, families can be bankrupted by the medical bills of one member under cancer treatment.

Just as we see with people, dogs do vary greatly in their pain tolerance; some are more stoic than others, who may border on hysteria because of fear as well as pain. This is where the experienced clinical eye of the veterinarian is invaluable to determine the best course of treatment and the animal patient's quality of life and chances of total or partial recovery.

Regardless of costs and affordability and the fact that some animal caregivers may seek to extend an animal's life for various personal reasons rather than for the animal's own sake, all involved have a duty to make the animal patient as comfortable as possible and give the animal a chance where there is a strong will to live.

Being nursed at home or setting up in-home palliative care with a visiting veterinarian may be preferable to long-term hospitalization where recovery may be protracted or arrested by separation anxiety and loss of the will to live.

Send all mail to animaldocfox@gmail.com or to Dr. Michael Fox in care of Universal Uclick, 1130 Walnut St., Kansas City, MO 64106. The volume of mail received prohibits personal replies, but questions and comments of general interest will be discussed in future columns. Visit Dr. Fox's website at http://www.drfoxvet.net.

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Concerns over paraplegic dog's treatment - INFORUM

Stem cell technology is a new and exciting branch of veterinary medicine. Stem cells are cells that can be safely harvested from a variety of adult animal tissues. Once harvested, the stem cells can be injected and induced to grow into a large number of different cell types.

Stem cell therapy offers the possibility of using these stem cells to grow into replacements for injured or diseased tissues such as bone, cartilage, muscle, nerves, and so on. What makes this such an exciting treatment option is that it allows us to introduce real tissue replacements for damaged tissues, rather than artificial replacement implants. Currently stem cell therapy for dogs is being used with some success to treat bone, joint, and ligament problems.

The technology involves the use of adult stem cells, which can be easily obtained, without any harm to the host animal from which they are taken. A small amount of adipose (fat) tissue is surgically removed from a host animal and a centrifuge is used to separate the stem cells from the fat tissue. The stem cells collected are then injected directly into the injured joint, ligament, or bone where they quickly begin to grow, replacing the damaged tissue with new, healthy tissue.

Stem cell therapy holds immense promise for becoming a viable treatment option for a variety of health issues dog's face.

At Bakerstown Animal Hospital, we believe that providing your canine companion with the highest quality medical care means being on the cutting edge of the latest technologies and procedures. This is reflected in every aspect of our approach to stem cell therapy for dogs. Our facilities feature state-of-the-art equipment, and our veterinary team stays up to date on the latest canine stem cell research available.

The ideal candidate for canine stem cell therapy is a dog in otherwise good health that suffers from arthritis or hip dysplasia, and who doesn't respond well to his or her medication. Or, a dog whose quality of life might further suffer due to invasive surgical procedures. Because canine stem cell therapy uses the patient's own tissues, a canine must be in overall good health in order for any collected stem cells to be effective.

Canine stem cells are collected through removing either fat cells, or various other applicable tissues from a dog's body. Within these tissues and cells exist regenerative cells that are known colloquially as dog stem cells. The regenerative cells that are collected do several things:

The best part is that canine stem cells are not synthetic cells being added to a living, biological organism. Rather, canine stem cells are a dog's own natural healing cells, Because of this, there is much less chance of rejection or adverse interaction, and there are also fewer potential side effects.

Due to the infancy of canine stem cell research and therapies, there is not yet a large body of information about possible adverse side effects. Just like any medical procedure, the risk for adverse side effects from dog stem cell therapy are ever-present. Risks could be associated with the tissue removal procedure, or from a patient's body rejecting the newly placed cells. Other issues with stem cell therapy for dogs include its effectiveness when used alone. This is because the prescription of traditional medication will accompany stem cell therapy procedures.

Deciding whether or not stem cell therapy for dogs is the right choice for your beloved canine companion is a very personal one. No matter what route you choose to take, we are here to help you make the decision that is in the best interest of your dog, and also that fits your budget and lifestyle.

At this time, most stem cell research for dogs currently focuses on treating bone, joint, and ligament problems, rather than treating more advanced illnesses and diseases. We are extremely confident that the day will come when many canine illnesses and diseases can be treated through advances in canine stem cell research.

One thing seems to be clear, stem cell research for dogs promises to revolutionize the veterinary industry, and is already showing good results with canines that have been treated with dog stem cells to repair joints, bones, or ligaments that have been damaged by injury or disease. We are here to help educate you about the latest canine stem cell research advances, and answer any other questions about dog stem cell therapy you might have.

If you would like to discuss how stem cell therapy can benefit your dog, please contact us to schedule an appointment. Our veterinary team can help you decide whether or not canine stem cell therapy is the right option, including discussing cost and prognosis.

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Stem Cell Therapy For Dogs - What you should know

A pair of English bulldog puppies are the first patients to be successfully treated with a unique therapy a combination of surgery and stem cells developed at the University of California, Davis, to help preserve lower-limb function in children with spina bifida.

Because dogs with the birth defect frequently have little control of their hindquarters, they also have little hope for a future. They are typically euthanized as puppies.

At their postsurgery re-check at 4 months old, however, the siblings, named Darla and Spanky, showed off their abilities to walk, run and play to their doctor,veterinary neurosurgeon Beverly Sturges.

The initial results of the surgery are promising, as far as hind limb control, said Sturges. Both dogs seemed to have improved range of motion and control of their limbs.

The dogs have since been adopted, and continue to do well at their home in New Mexico.

Spina bifida occurs when spinal tissue improperly fuses in utero, causing a range of cognitive, mobility, urinary and bowel disabilities in about 1,500 to 2,000 children born in the U.S. each year. The dogs procedure, which involved surgical techniques developed byfetal surgeon Diana Farmerof UC Davis Health together with a cellular treatment developed by stem cell scientistsAijun WangandDori Borjesson, director of the universitysVeterinary Institute for Regenerative Cures, represents a major step toward curing spina bifida for both humans and dogs.

Farmer pioneered the use of surgery prior to birth to improve brain development in children with spina bifida. She later showed that prenatal surgery combined with human placenta-derived mesenchymal stromal cells (PMSCs), held in place with a cellular scaffold, helped research lambs born with the disorder walk without noticeable disability.

Sturges wanted to find out if the surgery-plus-stem-cell approach could give dogs closer-to-normal lives along with better chances of survival and adoption. At 10-weeks old, Darla and Spanky were transported from Southern California Bulldog Rescue to the UC Davis veterinary hospital, where they were the first dogs to receive the treatment, this time using canine instead of human PMSCs.

Another distinction for Darla and Spanky is that their treatment occurred after birth, since prenatal diagnosis of spina bifida is not performed on dogs, Sturges explained. The disorder becomes apparent between 1 and 2 weeks of age, when puppies show hind-end weakness, poor muscle tone, incoordination and abnormal use of their tails.

UC Davis is the only place where this type of cross-disciplinary, transformational medicine could happen, according to Farmer.

Its rare to have a combination of excellent medical and veterinary schools and strong commitment to advancing stem cell science at one institution, she said.

UC Davis is also home to the One Healthinitiative aimed at finding novel treatmentslike thesefor diseases that affect both humans and animals.

Ive often said that I have the greatest job on the planet, because I get to help kids, Farmer said. Now my job is even better, because I get to help puppies too.

With additional evaluation and U.S. Food and Drug Administration approval, Farmer and Wang hope to test the therapy in human clinical trials. Sturges and Borjesson hope to do the same with a canine clinical trial. They hope the outcomes of their work help eradicate spina bifida in dogs and humans.

In the meantime, the team wants dog breeders to send more puppies with spina bifida to UC Davis for treatment and refinements that help the researchers fix an additional hallmark of spina bifida incontinence. While Darla and Spanky are very mobile and doing well on their feet, they still require diapers.

Further analysis of their progress will determine if the surgery improves their incontinence conditions, Sturges said.

Funding for this project was provided by the Veterinary Institute for Regenerative Cures (VIRC) at the UC Davis School of Veterinary Medicine, and the Surgical Bioengineering Lab at the UC Davis School of Medicine. Private donations to the veterinary school for stem cell research also contributed to this procedure. Farmer and Wangs spina bifida research is supported by funding from the National Institutes of Health, the California Institute for Regenerative Medicine, Shriners Hospitals for Children and the March of Dimes Foundation.

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Puppies benefit from stem cell treatment for children with spina bifida - University of California

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

said Takahashi.

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

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

Image: Annie Cavanagh / Wellcome Images

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

Posted Aug. 30, 2017

The AVMA House of Delegates passed a new policy July 21 on "Therapeutic Use of Stem Cells and Regenerative Medicine."

According to the policy: "Regenerative medicine is defined as the use of biological therapies including platelet rich-plasma, pluripotent stem cells, and multipotent stem cells to effect therapeutic benefit in disease states. While regenerative medicine holds promise of improvements in the treatment of a variety of diseases, many of which lack adequately effective treatments, questions remain. The AVMA supports the continued scientific development of these modalities while at the same time encouraging its members to employ caution with respect to their use.

"While data continue to accumulate suggesting therapeutic benefit from regenerative medicine, published peer-reviewed studies definitively documenting benefit are still lacking for many diseases. Nor has a scientific consensus for stem cell type, stem cell origin, dosage, transfer media, or method of administration been developed for each disease being treated. Despite these scientific insufficiencies, the adoption of regenerative medicine in the veterinary profession has grown rapidly. Unfortunately, some therapies being propounded and the processes and equipment being sold have outpaced the science which supports them. Veterinarians have few guidelines and limited resources for differentiating valid and effective therapies from ones which have insufficient data supporting the processes and/or therapies. Therefore, it is incumbent upon veterinarians engaged in regenerative therapies to be well versed in the emerging science of the field in order to successfully select the specific therapeutic protocols, processes, equipment, and vendors most likely to result in clinical benefit for their patients."

The policy lists nine considerations for use of regenerative medicine by veterinarians.

AVMA to deliberate on assistance animals, stem cells (June 1, 2017)

FDA finalizes guidance on cell-based products in animals (July 15, 2015)

Stem cells in theory & practice (Feb. 15, 2011)

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Policy addresses therapeutic use of stem cells, regenerative medicine - American Veterinary Medical Association

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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