Biotech, Stem Cell Therapy Animals & Veterinary Applications Majority of research is lead through veterinary practises This

This has enabled us to develop the human research side of things Many positive reasons to use it compared to traditional medicine Results of over 7000 international cases show that more than 80% recovered to a near level of that before their problems started. (mainly horses, dogs and cats currently)

Problems, illnesses and diseases that have been tackled include: o o o o Stroke Tendon & Ligament Damage Osteoarthritis Muscular Dystrophy (muscle disease)

Racehorses in particular have been a success of the research that stem cell therapy has been providing. Due to the nature and severity of the injuries they obtain, stem cell therapy has been a huge success for this area. Five primary mechanisms for stem cells: 1. 2. 3. 4. 5. Provides anti-inflammatory effects Homes to damaged tissue and recruits other cells necessary for tissue growth Supports tissue to grow over scar formations Inhibiting the death of cells due to apoptosis Differentiating into different cells, including bone, cartilage, tendon and ligament tissue.

Platelet-rich plasma can also be used along with stem-cell transplantation in order to make the process more efficient. Two main types of stem cell are used in research and treatment.
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Allogeneic Stem Cells. These cells are derived from a genetically different donor of the same species. Autologous Mesenchymal Stem Cells. These are found from the patient prior to use in other treatments.

A 3 category, Xenogenic Stem Cells, where the cells are taken from a different species is an area which is being looked into, but currently this is just being used for research. Sources http://www.vet-stem.com/science.php (diagram 2) http://www.medivet-america.com/ http://actcells.com/stem-cells-101/stem-cell-diagram/ (diagram 1) http://www.dailymail.co.uk/sciencetech/article-2235028/Scientists-reverse-paralysis-dogs-following-pioneering-celltreatment.html http://www.australianstemcells.com.au/ Dogs In regard to canine (dogs) arthritis, approximately 90% of owners of dogs treated for arthritis with pure' cultured stem cells have reported a substantial improvement in the condition (quality of life) of their dog with an average improvement grading of 75%. Horses

In clinical studies:Suspensory ligament injuries:Approximtely 75% of horses treated with suspensory ligament injuries returned to work at the prior level. In excess of 90% of horses treated returned to work with in excess of 70% returning to work at the prior level Joint disease:In excess of 80% of horses returned to work, with in excess of 50% returning to work at the prior level Tendon Injury:77% returned to work at the full prior level. AVSC believes that stem cell based therapies can significantly contribute to the improvement treatment of degenerative conditions and injuries in the veterinary setting. Differences in Regenerative Medicine compared to traditional medicine:

Does not rely on a single target receptor or a single pathway for its action Regenerative cell mixture is delivered either directly to the traumatic wound (e.g.: tendonitis, desmitis, fracture) or are delivered systemically (e.g.: liver disease, renal disease) Regenerative cells can differentiate into many tissue types, induce repair, and stimulate regeneration Regenerative cells "communicate" with the cells of their local environment through paracrine and autocrine 25 modalities, creating the optimal environment for natural healing Regenerative cells produce a variety of both secreted and cell surface substances that regulate tissue growth, integrity, and function

Sources of stem cells Research is currently underway to examine the differentiating capabilities of stem cells found in the umbilical cord, yolk sac and placenta of different animals. These stem cells are thought to have more differentiating ability than their adult counterparts, including the ability to more readily form tissues of endodermal and ectodermal origin. Joint repair Osteoarthritis is the main cause of joint pain both in animals and humans. Horses and dogs are most frequently affected arthritis. Natural cartilage regeneration is very limited and no current drug therapies are curative. Different types of mesenchymal stem cells and other additives are still being researched to find the best type of cell and method for long term treatment. There has been a lot of success recently injecting mesenchymal stem cells directly into the joint. This is a recently developed, non-invasive technique developed for easier clinical use. Dogs receiving this treatment showed greater flexibility in their joints and less pain. Bone defect repair Bone has a unique and well documented natural healing process that normally is sufficient to repair fractures and other common injuries. Misaligned breaks due to severe trauma, as well as things like tumor resections of bone cancer, are prone to improper healing if left to the natural process alone. Scaffolds composed of natural and artificial components are seeded with mesenchymal stem cells and placed in the defect. Within four weeks of placing the scaffold, newly formed bone begins to integrate with the old bone and within 32 weeks, full union is achieved. Further studies are necessary to fully characterize the use of cell-based therapeutics for treatment of bone fractures. Stem cells have also been used to treat degenerative bone diseases. The normally recommended treatment for dogs that have Legg-Calve-Perthes disease is to remove the head of the femur after the degeneration has progressed. Recently, mesenchymal stem cells have been injected directly in to the head of the femur, with success not only in bone regeneration, but also in pain reduction. Stem cells and muscle repairs Stem cells have successfully been used to ameliorate healing in the heart after myocardial infarction in dogs. Adipose and bone marrow derived stem cells were removed and induced to a cardiac cell fate before being injected into the heart. The heart was found to have improved contractility and a reduction in the damaged area four weeks after the stem cells were applied.
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A different trial is underway for a patch made of a porous substance on to which the stem cells are "seeded" in order to induce tissue regeneration in heart defects. Tissue was regenerated and the patch was well incorporated into the heart tissue. This is thought to be due, in part, to improved angiogenesis and reduction of inflammation. Although cardiomyocytes were produced from the mesenchymal stem cells, they did not appear to be contractile. Other treatments that induced a cardiac fate in the cells before transplanting had greater success at creating contractile heart tissue.
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Stem cells have been used recently to hasten the healing of skeletal muscle tears in working dogs. Traditional therapies rely on rest and anti-inflammatory treatments have been shown to permanently reduce the functioning in the muscle. Adipose derived stem cells were injected directly into the tear of the semitendinosus

muscle. Physical therapy was also completed during the healing process. Healing was observed much earlier than with traditional methods and the dogs were able to return to full work without any long term muscle damage. Stem cells and nervous system repairs Spinal cord injuries are one of the most common traumas brought into veterinary hospitals.
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Spinal injuries

occur in two ways after the trauma: the primary mechanical damage, and in secondary processes, like inflammation and scar formation, in the days following the trauma. These cells involved in the secondary damage response secrete factors that promote scar formation and inhibit cellular regeneration. Mesenchymal stem cells that are induced to a neural cell fate are loaded on to a porous scaffold and are then implanted at the site of injury. The cells and scaffold secrete factors that counteract those secreted by scar forming cells and promote neural regeneration. Eight weeks later, dogs treated with stem cells showed immense improvement over those treated with conventional therapies. Dogs treated with stem cells were able to occasionally support their own weight, which has not been seen in dogs undergoing conventional therapies.
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Treatments are also in clinical trials to repair and regenerate peripheral nerves. Peripheral nerves are more likely to be damaged, but the effects of the damage are not as widespread as seen in injuries to the spinal cord. Treatments are currently in clinical trials to repair severed nerves, with early success. Stem cells induced to a neural fate injected in to a severed nerve. Within four weeks, regeneration of previously damaged stem cells and completely formed nerve bundles were observed.
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Stem cells are also in clinical phases for treatment in ophthalmology. Hematopoietic stem cells have been used to treat corneal ulcers of different origin of several horses. These ulcers were resistant to conventional treatments available, but quickly responded positively to the stem-cell treatment. Stem cells were also able to restore sight in one eye of a horse with retinal detachment, allowing the horse to return to daily activities. Current areas of research Stems cells in the lab The ability to grow up functional adult tissues indefinitely in culture creates new opportunities for drug research. Researchers are able to grow up differentiated cell lines and then test new drugs on each cell type to examine possible interactions in vitro before performing in vivo studies. This is critical in the development of drugs for use in veterinary research because of the possibilities of species specific interactions. The hope is that having these cell lines available for research use will reduce the need for research animals used because affects on human tissuein vitro will provide insight not normally known before the animal testing phase.
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With the advent of induced pluripotent stem cells (iPSC), treatments being explored and created for the used in endangered low production animals possible. Rather than needing to harvest embryos or eggs, which are limited, the researchers can remove mesenchymal stem cells with greater ease and greatly reducing the danger to the animal due to noninvasive techniques. This allows the limited eggs to be put to use for reproductive purposes only Stem cells and conservation Stem cells are being explored for use in conservation efforts. Spermatogonial stem cells have been harvested from a rat and placed into a mouse host and fully mature sperm were produced with the ability to produce viable offspring. Currently research is underway to find suitable hosts for the introduction of donor spermatogonial

stem cells. If this becomes a viable option for conservationists, sperm can be produced from high genetic quality individuals who die before reaching sexual maturity, preserving a line that would otherwise be lost. Future clinical uses The use of stem cells for the treatment of liver disease in both humans and animals has been the focus of considerable interest. The liver has some natural regenerative properties, but is often insufficient to deal with the extent of some liver diseases. Hepatocytes have been formed from some sources of MSC, but they have not been applied clinically currently.
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There is a large effort to create stem cells differentiated along the pancreatic
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line as a possible cure for diabetes, but no line has been well established.

Mesenchymal stem cells are currently under clinical trials as a possible treatment for graft v. host disease and graft rejection after experiments on various animals showing that allogenic stem-cell treatments were not rejected and showed no difference in healing capabilities compared with autologous stem cells. This is being further researched for creating off-the-shelf allogenic stem-cell treatments for various aspects in regenerative veterinary medicine.
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Clinical trials are underway to explore the low immunogenic properties of stem cells and

their possible use for treatment of problems with an overactive immune system seen with allergies and autoimmune disorders.
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In recent years, US based stem cell clinics have emerged that treat patients with their own bone marrow or adipose derived adult stem cells as part of clinical trials or FDA authorized same day outpatient IRB programs, most notably for athletes to recover from osteoskeletal (bone, joint and connective tissue) related injuries. This emergence of US based human adult stem-cell therapy is discussed by Dr. Rudderham in his 2012 article Adult Stem Cell US Therapy.
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The long term impact of these treatments will need to be examined outside of their contribution to medicine.
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Vast improvements in veterinary medicine has allowed for companion and farm animals to live

longer lives. This, however, has contributed to the rise in injury and chronic illness in companion animals.
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Stem-cell treatments, especially for the treatment of orthopedic issues in horses, allows for working
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animals to return to a normal state of activity at a faster rate with a reduction in the re-injury rate.