Stem Cell Treatments

What are Stem Cells » Stem Cell Treatments

Stem cell treatments are a type of intervention strategy that introduces new adult stem cells into damaged tissue in order to treat disease or injury. Many medical researchers believe that stem cell treatments have the potential to change the face of human disease and alleviate suffering. The ability of stem cells to self-renew and give rise to subsequent generations with variable degrees of differentiation capacities, offers significant potential for generation of tissues that can potentially replace diseased and damaged areas in the body, with minimal risk of rejection and side effects.
A number of stem cell therapies exist, but most are at experimental stages or costly, with the notable exception of bone marrow transplantation.[citation needed] Medical researchers anticipate that adult and embryonic stem cells will soon be able to treat cancer, Type 1 diabetes mellitus, Parkinson's disease, Huntington's disease, Celiac Disease, cardiac failure, muscle damage and neurological disorders, and many others. Nevertheless, before stem cell therapeutics can be applied in the clinical setting, more research is necessary to understand stem cell behavior upon transplantation as well as the mechanisms of stem cell interaction with the diseased/injured microenvironment.

 Current treatments
Further information: Hematopoietic stem cell transplantation
For over 30 years, bone marrow, and more recently, umbilical cord blood stem cells, have been used to treat cancer patients with conditions such as leukaemia and lymphoma. During chemotherapy, most growing cells are killed by the cytotoxic agents. These agents, however, cannot discriminate between the leukaemia or neoplastic cells, and the hematopoietic stem cells within the bone marrow. It is this side effect of conventional chemotherapy strategies that the stem cell transplant attempts to reverse; a donor's healthy bone marrow reintroduces functional stem cells to replace the cells lost in the host's body during treatment.
 Potential treatments
 Brain damage
Stroke and traumatic brain injury lead to cell death, characterized by a loss of neurons and oligodendrocytes within the brain. Healthy adult brains contain neural stem cells which divide to maintain general stem cell numbers, or become progenitor cells. In healthy adult animals, progenitor cells migrate within the brain and function primarily to maintain neuron populations for olfaction (the sense of smell). In pregnancy and after injury, this system appears to be regulated by growth factors and can increase the rate at which new brain matter is formed.[citation needed] Although the reparative process appears to initiate following trauma to the brain, substantial recovery is rarely observed in adults, suggesting a lack of robustness.
Stem cells may also be used to treat brain degeneration, such as in Parkinson's and Alzheimer's disease.
The development of gene therapy strategies for treatment of intra-cranial tumours offers much promise, and has shown to be successful in the treatment of some dogs; although research in this area is still at an early stage. Using conventional techniques, brain cancer is difficult to treat because it spreads so rapidly. Researchers at the Harvard Medical School transplanted human neural stem cells into the brain of rodents that received intracranial tumours. Within days, the cells migrated into the cancerous area and produced cytosine deaminase, an enzyme that converts a non-toxic pro-drug into a chemotheraputic agent. As a result, the injected substance was able to reduce the tumor mass by 81 percent. The stem cells neither differentiated nor turned tumorigenic. Some researchers believe that the key to finding a cure for cancer is to inhibit proliferation of cancer stem cells. Accordingly, current cancer treatments are designed to kill cancer cells. However, conventional chemotherapy treatments cannot discriminate between cancerous cells and others. Stem cell therapies may serve as potential treatments for cancer. Research on treating Lymphoma using adult stem cells is underway and has had human trials. Essentially, chemotherapy is used to completely destroy the patients own lymphocytes, and stem cells injected, eventually replacing the immune system of the patient with that of the healthy donor.
 Spinal cord injury
A team of Korean researchers reported on November 25, 2003, that they had transplanted multipotent adult stem cells from umbilical cord blood to a patient suffering from a spinal cord injury and that following the procedure, she could walk on her own, without difficulty. The patient had not been able to stand up for roughly 19 years. For the unprecedented clinical test, the scientists isolated adult stem cells from umbilical cord blood and then injected them into the damaged part of the spinal cord.
According to the October 7, 2005 issue of The Week, University of California, Irvine researchers transplanted multipotent human fetal-derived neural stem cells into paralyzed mice, resulting in locomotor improvements four months later. The observed recovery was associated with differentiation of transplanted cells into new neurons and oligodendrocytes- the latter of which forms the myelin sheath around axons of the central nervous system, thus insulating neural impulses and facilitating communication with the brain.
In January 2005, researchers at the University of Wisconsin–Madison differentiated human blastocyst stem cells into neural stem cells, then into pre-mature motor neurons, and finally into spinal motor neurons, the cell type that, in the human body, transmits messages from the brain to the spinal cord and subsequently mediates motor function in the periphery. The newly generated motor neurons exhibited electrical activity, the signature action of neurons. Lead researcher Su-Chun Zhang described the process as "[teaching] the blastocyst stem cells to change step by step, where each step has different conditions and a strict window of time."
Transformation of blastocyst stem cells into motor neurons had eluded researchers for decades. While Zhang's findings were a significant contribution to the field, the ability of transplanted neural cells to establish communication with neighboring cells remains unclear. Accordingly, studies using chicken embryos as a model organism can be an effective proof-of-concept experiment. If functional, the new cells could be used to treat diseases like Lou Gehrig's disease, muscular dystrophy, and spinal cord injuries.[citation needed]
 Heart damage
Several clinical trials targeting heart disease have shown that adult stem cell therapy is safe, effective, and equally efficient in treating old and recent infarcts. While initial animal studies demonstrated remarkable therapeutic effects, later clinical trials achieved only modest, though statistically significant, improvements. Possible reasons for this discrepancy are patient age, timing of treatment and the recent occurrence of a myocardial infarction. These obstacles may be bypassed by additional treatments to the transplanted stem cells or the patient which increase the effectiveness of the treatment or by optimizing the methodology. Current studies vary greatly in cell procuring techniques, cell types, cell administration timing and procedures, and studied parameters, making it very difficult to make comparisons. Comparative studies are therefore currently needed. Stem cell therapy for treatment of myocardial infarction usually makes use of autologous bone marrow stem cells (a specific type or all), however other types of adult stem cells may be used, such as adipose-derived stem cells. Adult stem cell therapy for treating heart disease was commercially available in at least five continents at the last count (2007).
Possible mechanisms of recovery include:
 Generation of heart muscle cells
 Stimulation of growth of new blood vessels to repopulate damaged heart tissue
 Secretion of growth factors
 Assistance via some other mechanism
It may be possible to have adult bone marrow cells differentiate into heart muscle cells.
The first successful integration of human embryonic-stem-cell-derived cardiomyocytes in guinea pigs (mouse hearts beat too fast) was reported in August 2012. The contraction strength was measured four weeks after the guinea pigs underwent simulated heart attacks and cell treatment. The cells contracted synchronously with the existing cells, but it is unknown if the positive results were produced mainly from paracrine as opposed to direct electromechanical effects from the human cells. Future work will focus on how to get the cells to engraft more strongly around the scar tissue. Whether treatments from embryonic or adult bone marrow stem cells will prove more effective remains to be seen.
 Haematopoiesis (blood cell formation)
The specificity of the human immune cell repertoire is what allows the human body to defend itself from rapidly adapting antigens. However, the immune system is vulnerable to degradation upon the pathogenesis of disease, and because of the critical role that it plays in overall defense, its degradation is often fatal to the organism as a whole. Diseases of hematopoietic cells are called hematopathology. The specificity of the immune cells is what allows recognition of foreign antigens, causing further challenges in the treatment of immune disease. Identical matches between donor and recipient must be made for successful transplantation treatments, but matches are uncommon, even between first-degree relatives. Research using both hematopoietic adult stem cells and embryonic stem cells has provided insight into the possible mechanisms and methods of treatment for many of these ailments.[citation needed]
Fully mature human red blood cells may be generated ex vivo by hematopoietic stem cells (HSCs), which are precursors of red blood cells. In this process, HSCs are grown together with stromal cells, creating an environment that mimics the conditions of bone marrow, the natural site of red blood cell growth. Erythropoietin, a growth factor, is added, coaxing the stem cells to complete terminal differentiation into red blood cells. Further research into this technique should have potential benefits to gene therapy, blood transfusion, and topical medicine.
Hair follicles also contain stem cells, and some researchers predict research on these follicle stem cells may lead to successes in treating baldness through an activation of the stem cells progenitor cells. This treatment is expected to work by activating already existing stem cells on the scalp. Later treatments may be able to simply signal follicle stem cells to give off chemical signals to nearby follicle cells which have shrunk during the aging process, which in turn respond to these signals by regenerating and once again making healthy hair. Most recently, Dr. Aeron Potter of the University of California has claimed that stem cell therapy led to a significant and visible improvement in follicular hair growth[citation needed]. Results from his experiments are under review by the journal Science (journal).
 Missing teeth
In 2004, scientists at King's College London discovered a way to cultivate a complete tooth in mice and were able to grow them stand-alone in the laboratory. Researchers are confident that this technology can be used to grow live teeth in human patients.
In theory, stem cells taken from the patient could be coaxed in the lab into turning into a tooth bud which, when implanted in the gums, will give rise to a new tooth, and would be expected to grow within two months. It will fuse with the jawbone and release chemicals that encourage nerves and blood vessels to connect with it. The process is similar to what happens when humans grow their original adult teeth.
Many challenges remain, however, before stem cells could be a choice for the replacement of missing teeth in the future.
Heller has reported success in re-growing cochlea hair cells with the use of embryonic stem cells.
 Blindness and vision impairment
Since 2003, researchers have successfully transplanted corneal stem cells into damaged eyes to restore vision. "Sheets of retinal cells used by the team are harvested from aborted fetuses, which some people find objectionable." When these sheets are transplanted over the damaged cornea, the stem cells stimulate renewed repair, eventually restore vision. The latest such development was in June 2005, when researchers at the Queen Victoria Hospital of Sussex, England were able to restore the sight of forty patients using the same technique. The group, led by Dr. Sheraz Daya, was able to successfully use adult stem cells obtained from the patient, a relative, or even a cadaver. Further rounds of trials are ongoing.
In April 2005, doctors in the UK transplanted corneal stem cells from an organ donor to the cornea of Deborah Catlyn, a woman who was blinded in one eye when acid was thrown in her eye at a nightclub. The cornea, which is the transparent window of the eye, is a particularly suitable site for transplants. In fact, the first successful human transplant was a cornea transplant. The absence of blood vessels within the cornea makes this area a relatively easy target for transplantation. The majority of corneal transplants carried out today are due to a degenerative disease called keratoconus.
The University Hospital of New Jersey reports that the success rate for growth of new cells from transplanted stem cells varies from 25 percent to 70 percent.
In 2009, researchers at the University of Pittsburgh Medical center demonstrated that stem cells collected from human corneas can restore transparency without provoking a rejection response in mice with corneal damage.
In January 2012, The Lancet published a paper by Dr. Steven Schwartz, at UCLA's Jules Stein Eye Institute, reporting two women who had gone legally blind from macular degeneration had dramatic improvements in their vision after retinal injections of human embryonic stem cells. A team of doctors lead by Dr. Virender Singh Sangwan, have developed a lab free technique of regenerating stem cells using tea bag or sprinkler approach.
 Amyotrophic lateral sclerosis
Stem cells have resulted in significant locomotor improvements in rats with an Amyotrophic lateral sclerosis-like disease. In a rodent model that closely mimics the human form of ALS, animals were injected with a virus to kill the spinal cord motor nerves which mediate movement. Animals subsequently received stem cells in the spinal cord. Transplanted cells migrated to the sites of injury, contributed to regeneration of the ablated nerve cells, and restored locomotor function.
 Graft vs. host disease and Crohn's disease
Phase III clinical trials expected to end in second-quarter 2008 were conducted by Osiris Therapeutics using their in-development product Prochymal, derived from adult bone marrow. The target disorders of this therapeutic are graft-versus-host disease and Crohn's disease.
 Neural and behavioral birth defects


This section needs additional citations for verification. (August 2010)

A team of researchers led by Prof. Joseph Yanai were able to reverse learning deficits in the offspring of pregnant mice who were exposed to heroin and the pesticide organophosphate. This was done by direct neural stem cell transplantation into the brains of the offspring. The recovery was almost 100 percent, as shown both in behavioral tests and objective brain chemistry tests. Behavioral tests and learning scores of the treated mice showed rapid improvement after treatment, providing results that rivaled non-treated mice. On the molecular level, brain chemistry of the treated animals was also restored to normal. Through the work, which was supported by the US National Institutes of Health, the US-Israel Binational Science Foundation and the Israel anti-drug authorities, the researchers discovered that the stem cells worked even in cases where most of the cells died out in the host brain.
The scientists found that before they die the neural stem cells succeed in inducing the host brain to produce large numbers of stem cells which repair the damage. These findings, which answered a major question in the stem cell research community, were published in January 2008 in the leading journal, Molecular Psychiatry. Scientists are now developing procedures to administer the neural stem cells in the least invasive way possible - probably via blood vessels, making therapy practical and clinically feasible. Researchers also plan to work on developing methods to take cells from the patient's own body, turn them into stem cells, and then transplant them back into the patient's blood via the blood stream. Aside from decreasing the chances of immunological rejection, the approach will also eliminate the controversial ethical issues involved in the use of stem cells from human embryos.
Diabetes patients lose the function of insulin-producing beta cells within the pancreas. Human embryonic stem cells may be grown in cell culture and stimulated to form insulin-producing cells that can be transplanted into the patient.
However, clinical success is highly dependent on the development of the following procedures:
 Transplanted cells should proliferate
 Transplanted cells should differentiate in a site-specific manner
 Transplanted cells should survive in the recipient (prevention of transplant rejection)
 Transplanted cells should integrate within the targeted tissue
 Transplanted cells should integrate into the host circuitry and restore function
Clinical case reports in the treatment orthopaedic conditions have been reported. To date, the focus in the literature for musculoskeletal care appears to be on mesenchymal stem cells. Centeno et al. have published MRI evidence of increased cartilage and meniscus volume in individual human subjects. The results of trials that include a large number of subjects, are yet to be published. However, a published safety study conducted in a group of 227 patients over a 3-4 year period shows adequate safety and minimal complications associated with mesenchymal cell transplantation.
Wakitani has also published a small case series of nine defects in five knees involving surgical transplantation of mesenchymal stem cells with coverage of the treated chondral defects.
 Wound healing
Stem cells can also be used to stimulate the growth of human tissues. In an adult, wounded tissue is most often replaced by scar tissue, which is characterized in the skin by disorganized collagen structure, loss of hair follicles and irregular vascular structure. In the case of wounded fetal tissue, however, wounded tissue is replaced with normal tissue through the activity of stem cells. A possible method for tissue regeneration in adults is to place adult stem cell "seeds" inside a tissue bed "soil" in a wound bed and allow the stem cells to stimulate differentiation in the tissue bed cells. This method elicits a regenerative response more similar to fetal wound-healing than adult scar tissue formation. Researchers are still investigating different aspects of the "soil" tissue that are conducive to regeneration.
Culture of human embryonic stem cells in mitotically inactivated porcine ovarian fibroblasts (POF) causes differentiation into germ cells (precursor cells of oocytes and spermatozoa), as evidenced by gene expression analysis.
Human embryonic stem cells have been stimulated to form Spermatozoon-like cells, yet still slightly damaged or malformed. It could potentially treat azoospermia.
In 2012, oogonial stem cells were isolated from adult mouse and human ovaries and demonstrated to be capable of forming mature oocytes. These cells have the potential to treat infertility.
 Clinical Trials
On January 23, 2009, the US Food and Drug Administration gave clearance to Geron Corporation for the initiation of the first clinical trial of an embryonic stem cell-based therapy on humans. The trial aimed evaluate the drug GRNOPC1, embryonic stem cell-derived oligodendrocyte progenitor cells, on patients with acute spinal cord injury. The trial was discontinued in November 2011 so that the company could focus on therapies in the "current environment of capital scarcity and uncertain economic conditions".

As of mid 2010 hundreds of phase III clinical trials involving stem cells have been registered.
 Stem cell use in animals
 Veterinary applications
 Potential contributions to veterinary medicine
 Research currently conducted on horses, dogs, and cats can benefit the development of stem-cell treatments in veterinary medicine and can target a wide range of injuries and diseases such as myocardial infarction, stroke, tendon and ligament damage, osteoarthritis, osteochondrosis and muscular dystrophy both in large animals, as well as humans. While investigation of cell-based therapeutics generally reflects human medical needs, the high degree of frequency and severity of certain injuries in racehorses has put veterinary medicine at the forefront of this novel regenerative approach. Companion animals can serve as clinically relevant models that closely mimic human disease.
 Development of regenerative treatment models
 While further studies are necessary to fully characterize the use of cell-based therapeutics for treatment of bone fractures, stem cells are thought to mediate repair via five primary mechanisms: 1) providing an antiinflammatory effect, 2) homing to damaged tissues and recruiting other cells, such as endothelial progenitor cells, that are necessary for tissue growth, 3) supporting tissue remodeling over scar formation, 4) inhibiting apoptosis, and 5) differentiating into bone, cartilage, tendon, and ligament tissue. To further enrich blood supply to the damaged areas, and consequently promote tissue regeneration, platelet-rich plasma could be used in conjunction with stem cell transplantation. The efficacy of some stem cell populations may also be affected by the method of delivery; for instance, to regenerate bone, stem cells are often introduced in a scaffold where they produce the minerals necessary for generation of functional bone. Stem cells have also been shown to have a low immunogenicity due to the relatively low number of MHC molecules found on their surface. In addition, they have been found to secrete chemokines that alter the immune response and promote tolerance of the new tissue. This allows for allogeneic treatments to be performed without a high rejection risk.
 Sources of stem cells
 Veterinary applications of stem cell therapy as a means of tissue regeneration have been largely shaped by research that began with the use of adult-derived mesenchymal stem cells to treat animals with injuries or defects affecting bone, cartilage, ligaments and/or tendons. There are two main categories of stem cells used for treatments: allogeneic stem cells derived from a genetically different donor within the same species and autologous mesenchymal stem cells, derived from the patient prior to use in various treatments. A third category, xenogenic stem cells, or stem cells derived from different species, are used primarily for research purposes, especially for human treatments. Most stem cells intended for regenerative therapy are generally isolated either from the patient's bone marrow or from adipose tissue. Mesenchymal stem cells can differentiate into the cells that make up bone, cartilage, tendons, and ligaments, as well as muscle, neural and other progenitor tissues, they have been the main type of stem cells studied in the treatment of diseases affecting these tissues. The number of stem cells transplanted into damaged tissue may alter efficacy of treatment. Accordingly, stem cells derived from bone marrow aspirates, for instance, are cultured in specialized laboratories for expansion to millions of cells. Although adipose-derived tissue also requires processing prior to use, the culturing methodology for adipose-derived stem cells is not as extensive as that for bone marrow-derived cells. While it is thought that bone-marrow derived stem cells are preferred for bone, cartilage, ligament, and tendon repair, others believe that the less challenging collection techniques and the multi-cellular microenvironment already present in adipose-derived stem cell fractions make the latter the preferred source for autologous transplantation.. New sources of mesenchymal stem cells are currently being researched, including stem cells present in the skin and dermis which are of interest because of the ease at which they can be harvested with minimal risk to the animal. Hematopoetic stem cells have also been discovered to be travelling in the blood stream and possess equal differentiating ability as other mesenchymal stem cells, again with a very non-invasive harvesting technique. There has been more recent interest in the use of extra embryonic mesenchymal 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. 
 Stem cells and Soft Tissue Repair
 Because of the general positive healing capabilities of stem cells, they have gained interest for the treatment of cutaneous wounds. This is important interest for those with reduced healing capabilities, like diabetics and those undergoing chemotherapy. In one trial, stem cells were isolated from the Wharton’s jelly of the umbilical cord. These cells were injected directly into the wounds. Within a week, full re-epithelialization of the wounds had occurred, compared to minor re-epithelialization in the control wounds. This also showed the capabilities of mesenchymal stem cells in the repair of epidermal tissues. Soft palate defects in horses are caused by a failure of the embryo to fully close at the midline during embryogenesis. These are often not found until after they have become worse because of the difficulty in visualizing the entire soft palate. This lack of visualization is thought to also contribute to the low success rate in surgical intervention to repair the defect. As a result, the horse often has to be euthanized. Recently, the use of mesenchymal stem cells has been added to the conventional treatments. After the surgeon has sutured the palate closed, autologous mesenchymal cells are injected into the soft palate. The stem cells were found to be integrated into the healing tissue especially along the border with the old tissue. There was also a large reduction in the number of inflammatory cells present, which is thought to aid in the healing process. 
 Stem Cells and Orthopedic Repairs
 Autologous stem cell-based treatments for ligament injury, tendon injury, osteoarthritis, osteochondrosis, and sub-chondral bone cysts have been commercially available to practicing veterinarians to treat horses since 2003 in the United States and since 2006 in the United Kingdom. Autologous stem-cell based treatments for tendon injury, ligament injury, and osteoarthritis in dogs have been available to veterinarians in the United States since 2005. Over 3000 privately-owned horses and dogs have been treated with autologous adipose-derived stem cells. The efficacy of these treatments has been shown in double-blind clinical trials for dogs with osteoarthritis of the hip and elbow and horses with tendon damage.

 Tendon Repair
 Race horses are especially prone to injuries of the tendon and ligaments. Conventional therapies are very unsuccessful in returning the horse to full functioning potential. Natural healing, guided by the conventional treatments, leads to the formation of fibrous scar tissue that reduces flexibility and full joint movement. Traditional treatments prevented a large number of horses from returning to full activity and also have a high incidence of re-injury due to the stiff nature of the scarred tendon. Introduction of both bone marrow and adipose derived stem cells, along with natural mechanical stimulus promoted the regeneration of tendon tissue. The natural movement promoted the alignment of the new fibers and tendocytes with the natural alignment found in uninjured tendons. Stem cell treatment not only allowed more horses to return to full duty and also greatly reduced the re-injury rate over a three year period. More recently, the use of embryonic stem cells has also been applied to tendon repair. The embryonic stem cells were shown to have a better survival rate in the tendon as well as better migrating capabilities to reach all areas of damaged tendon. The overall repair quality was also higher, with better tendon architecture and collagen formed. There was also no tumor formation seen during the three month experimental period. Long term studies need to be carried out to examine the long term efficacy and risks associated with the use of embryonic stem cells. Similar results have been found in small animals.
 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, but rather look to reduce the symptoms associated with the degeneration. 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. Adipose-derived mesenchymal cells are currently the most often used because of the non-invasive harvesting. 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. 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 are 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. 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. 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. 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. 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. 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 tissue in vitro will provide insight not normally known before the animal testing phase. 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. There is a large effort to create stem cells differentiated along the pancreatic 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. 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. 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. The long term impact of these treatments will need to be examined outside of their contribution to medicine. 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. Stem cell treatments, especially for the treatment of orthopedic issues in horses, allows for working animals to return to a normal state of activity at a faster rate with a reduction in the re-injury rate.