Stem cell treatments
Encyclopedia
Stem cell treatments are a type of intervention strategy that introduces new 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 cell
Stem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...

s 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.

See also: Cell therapy
Cell therapy
Cell therapy describes the process of introducing new cells into a tissue in order to treat a disease. Cell therapies often focus on the treatment of hereditary diseases, with or without the addition of gene therapy...



A number of stem cell
Stem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...

 therapies exist, but most are at experimental stages or costly, with the notable exception of bone marrow transplantation. Medical researchers anticipate that adult and embryonic stem cell
Embryonic stem cell
Embryonic stem cells are pluripotent stem cells derived from the inner cell mass of the blastocyst, an early-stage embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consist of 50–150 cells...

s will soon be able to treat cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

, Type 1 diabetes mellitus, Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...

, Huntington's disease
Huntington's disease
Huntington's disease, chorea, or disorder , is a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and dementia. It typically becomes noticeable in middle age. HD is the most common genetic cause of abnormal involuntary writhing movements called chorea...

, Celiac Disease, cardiac failure, muscle
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...

 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

For over 30 years, bone marrow, and more recently, umbilical cord blood stem cells, have been used to treat cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

 patients with conditions such as leukemia
Leukemia
Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...

 and lymphoma
Lymphoma
Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...

. During chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....

, most growing cells are killed by the cytotoxic agents. These agents, however, cannot discriminate between the leukemia 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.

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 cell
Neural stem cell
Neural stem cells are the self-renewing, multipotent cells that generate the main phenotypes of the nervous system. In 1989, Sally Temple described multipotent, self-renewing progenitor and stem cells in the subventricular zone of the mouse brain . In 1992, Brent A...

s 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). Interestingly, 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. 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
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...

 and Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...

.

Cancer

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
Harvard Medical School
Harvard Medical School is the graduate medical school of Harvard University. It is located in the Longwood Medical Area of the Mission Hill neighborhood of Boston, Massachusetts....

 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
Cytosine deaminase
In enzymology, a cytosine deaminase is an enzyme that catalyzes the chemical reactionThus, the two substrates of this enzyme are cytosine and H2O, whereas its two products are uracil and NH3....

, 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
Cellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...

 nor turned tumorigenic.
Some researchers believe that the key to finding a cure for cancer is to inhibit proliferation of cancer stem cell
Cancer stem cell
Cancer stem cells are cancer cells that possess characteristics associated with normal stem cells, specifically the ability to give rise to all cell types found in a particular cancer sample. CSCs are therefore tumorigenic , perhaps in contrast to other non-tumorigenic cancer cells...

s. 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
Spinal cord injury
A spinal cord injury refers to any injury to the spinal cord that is caused by trauma instead of disease. Depending on where the spinal cord and nerve roots are damaged, the symptoms can vary widely, from pain to paralysis to incontinence...

 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
The Week
The Week, styled as THE WEEK, is a weekly news magazine.-History:It was founded in the United Kingdom by Jolyon Connell in 1995. In April 2001, the magazine began publishing an American edition; an Australian edition followed in October 2008. Dennis Publishing publishes the U.K. and Australian...

, University of California, Irvine
University of California, Irvine
The University of California, Irvine , founded in 1965, is one of the ten campuses of the University of California, located in Irvine, California, USA...

 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
University of Wisconsin–Madison
The University of Wisconsin–Madison is a public research university located in Madison, Wisconsin, United States. Founded in 1848, UW–Madison is the flagship campus of the University of Wisconsin System. It became a land-grant institution in 1866...

 differentiated human blastocyst stem cells into neural stem cells, then into pre-mature motor neuron
Motor neuron
In vertebrates, the term motor neuron classically applies to neurons located in the central nervous system that project their axons outside the CNS and directly or indirectly control muscles...

s, and finally into spinal motor neurons, the cell type that, in the human body, transmits message
Message
A message in its most general meaning is an object of communication. It is a vessel which provides information. Yet, it can also be this information. Therefore, its meaning is dependent upon the context in which it is used; the term may apply to both the information and its form...

s from the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...

 to the spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...

 and subsequently mediates motor function in the periphery. The newly generated motor neurons exhibited electrical activity, the signature action of neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

s. 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 disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...

s like Lou Gehrig's disease, muscular dystrophy
Muscular dystrophy
Muscular dystrophy is a group of muscle diseases that weaken the musculoskeletal system and hamper locomotion. Muscular dystrophies are characterized by progressive skeletal muscle weakness, defects in muscle proteins, and the death of muscle cells and tissue.In the 1860s, descriptions of boys who...

, and spinal cord injuries.

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. 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.

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
Hematopathology
Hematopathology is the branch of pathology which studies diseases of hematopoietic cells . In the United States, hematopathology is a board certified subspecialty practiced by those physicians who have completed general pathology residency and additional fellowship training in...

. 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.

Fully mature human red blood cells may be generated ex vivo
Ex vivo
Ex vivo means that which takes place outside an organism. In science, ex vivo refers to experimentation or measurements done in or on tissue in an artificial environment outside the organism with the minimum alteration of natural conditions...

by hematopoietic stem cells (HSCs), which are precursors of red blood cells. In this process, HSCs are grown together with stromal cell
Stromal cell
In cell biology, stromal cells are connective tissue cells of any organ, for example in the uterine mucosa , prostate, bone marrow, and the ovary. They are cells that support the function of the parenchymal cells of that organ...

s, creating an environment that mimics the conditions of bone marrow, the natural site of red blood cell growth. Erythropoietin
Erythropoietin
Erythropoietin, or its alternatives erythropoetin or erthropoyetin or EPO, is a glycoprotein hormone that controls erythropoiesis, or red blood cell production...

, a growth factor
Growth factor
A growth factor is a naturally occurring substance capable of stimulating cellular growth, proliferation and cellular differentiation. Usually it is a protein or a steroid hormone. Growth factors are important for regulating a variety of cellular processes....

, 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.

Baldness

Hair
Hair
Hair is a filamentous biomaterial, that grows from follicles found in the dermis. Found exclusively in mammals, hair is one of the defining characteristics of the mammalian class....

 follicles also contain stem cells, and some researchers predict research on these follicle stem cells may lead to successes in treating baldness
Baldness
Baldness implies partial or complete lack of hair and can be understood as part of the wider topic of "hair thinning". The degree and pattern of baldness can vary greatly, but its most common cause is male and female pattern baldness, also known as androgenic alopecia, alopecia androgenetica or...

 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
University of California
The University of California is a public university system in the U.S. state of California. Under the California Master Plan for Higher Education, the University of California is a part of the state's three-tier public higher education system, which also includes the California State University...

 has claimed that stem cell therapy led to a significant and visible improvement in follicular hair growth . Results from his experiments are under review by the journal Science (journal)
Science (journal)
Science is the academic journal of the American Association for the Advancement of Science and is one of the world's top scientific journals....

.

Missing teeth

In 2004, scientists at King's College London
King's College London
King's College London is a public research university located in London, United Kingdom and a constituent college of the federal University of London. King's has a claim to being the third oldest university in England, having been founded by King George IV and the Duke of Wellington in 1829, and...

 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.

Deafness

Heller has reported success in re-growing cochlea hair cells with the use of embryonic stem cell
Embryonic stem cell
Embryonic stem cells are pluripotent stem cells derived from the inner cell mass of the blastocyst, an early-stage embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consist of 50–150 cells...

s.

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
Cornea
The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Together with the lens, the cornea refracts light, with the cornea accounting for approximately two-thirds of the eye's total optical power. In humans, the refractive power of the cornea is...

, the stem cells stimulate renewed repair, eventually restore vision. The latest such development was in June 2005, when researchers at the Queen Victoria Hospital
Queen Victoria Hospital
The Queen Victoria Hospital, located in East Grinstead, West Sussex, England is the specialist reconstructive surgery centre for the south east of England, and also provides services at clinics across the region. It has become world famous for its pioneering burns and plastic surgery. The 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
Cadaver
A cadaver is a dead human body.Cadaver may also refer to:* Cadaver tomb, tomb featuring an effigy in the form of a decomposing body* Cadaver , a video game* cadaver A command-line WebDAV client for Unix....

. Further rounds of trials are ongoing.

In April 2005, doctors in the UK transplanted corneal stem cells from an organ donor to the cornea
Cornea
The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Together with the lens, the cornea refracts light, with the cornea accounting for approximately two-thirds of the eye's total optical power. In humans, the refractive power of the cornea is...

 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
Cornea transplant
Corneal transplantation, also known as corneal grafting, is a surgical procedure where a damaged or diseased cornea is replaced by donated corneal tissue in its entirety or in part...

. 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
Keratoconus
Keratoconus , is a degenerative disorder of the eye in which structural changes within the cornea cause it to thin and change to a more conical shape than its normal gradual curve....

.

The University Hospital
The University Hospital (Newark, New Jersey)
The University Hospital is the teaching hospital of the New Jersey Medical School in Newark, New Jersey.-Overview:The University Hospital is owned and operated by the University of Medicine and Dentistry of New Jersey , and is the primary teaching hospital of the New Jersey Medical School, a school...

 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.

Amyotrophic lateral sclerosis

Stem cells have resulted in significant locomotor improvements in rats with an Amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis , also referred to as Lou Gehrig's disease, is a form of motor neuron disease caused by the degeneration of upper and lower neurons, located in the ventral horn of the spinal cord and the cortical neurons that provide their efferent input...

-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
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...

. The target disorders of this therapeutic are graft-versus-host disease
Graft-versus-host disease
Graft-versus-host disease is a common complication after a stem cell transplant or bone marrow transplant from another person . Immune cells in the donated marrow or stem cells recognize the recipient as "foreign". The transplanted immune cells then attack the host's body cells...

 and Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...

.

Neural and behavioral birth defects

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
Organophosphate
An organophosphate is the general name for esters of phosphoric acid. Phosphates are probably the most pervasive organophosphorus compounds. Many of the most important biochemicals are organophosphates, including DNA and RNA as well as many cofactors that are essential for life...

. 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
Molecular Psychiatry
Molecular Psychiatry is a scientific journal published by Nature Publishing Group.It publishes papers in biological psychiatry and, e.g., about psychiatric genetics...

. 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

Diabetes patients lose the function of insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....

-producing beta cell
Beta cell
Beta cells are a type of cell in the pancreas located in the so-called islets of Langerhans. They make up 65-80% of the cells in the islets.-Function:...

s 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
    Transplant rejection
    Transplant rejection occurs when transplanted tissue is rejected by the recipient's immune system, which destroys the transplanted tissue. Transplant rejection can be lessened by determining the molecular similitude between donor and recipient and by use of immunosuppressant drugs after...

    )
  • Transplanted cells should integrate within the targeted tissue
  • Transplanted cells should integrate into the host circuitry and restore function

Orthopaedics

Clinical case reports in the treatment of 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.

Infertility

Culture of human embryonic stem cells in mitotically inactivated porcine ovarian fibroblasts (POF) causes differentiation into germ cell
Germ cell
A germ cell is any biological cell that gives rise to the gametes of an organism that reproduces sexually. In many animals, the germ cells originate near the gut of an embryo and migrate to the developing gonads. There, they undergo cell division of two types, mitosis and meiosis, followed by...

s (precursor cells of oocytes and spermatozoa), as evidenced by gene expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...

 analysis.

Human embryonic stem cells have been stimulated to form Spermatozoon
Spermatozoon
A spermatozoon is a motile sperm cell, or moving form of the haploid cell that is the male gamete. A spermatozoon joins an ovum to form a zygote...

-like cells, yet still slightly damaged or malformed. It could potentially treat azoospermia
Azoospermia
Azoospermia is the medical condition of a male not having any measurable level of sperm in his semen. It is associated with very low levels of fertility or even sterility, but many forms are amenable to medical treatment...

.

Clinical Trials

On January 23, 2009, the US Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...

 gave clearance to Geron Corporation for the initiation of the first clinical trial of an embryonic stem cell-based therapy on humans. The trial will evaluate the drug GRNOPC1, embryonic stem cell
Embryonic stem cell
Embryonic stem cells are pluripotent stem cells derived from the inner cell mass of the blastocyst, an early-stage embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consist of 50–150 cells...

-derived oligodendrocyte
Oligodendrocyte
Oligodendrocytes , or oligodendroglia , are a type of brain cell. They are a variety of neuroglia. Their main function is the insulation of axons in the central nervous system of some vertebrates...

 progenitor cells, on patients with acute spinal cord injury
Spinal cord injury
A spinal cord injury refers to any injury to the spinal cord that is caused by trauma instead of disease. Depending on where the spinal cord and nerve roots are damaged, the symptoms can vary widely, from pain to paralysis to incontinence...

.

As of mid 2010 hundreds of phase III clinical trials involving stem cells have been registered.

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
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...

, stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...

, tendon
Tendon
A tendon is a tough band of fibrous connective tissue that usually connects muscle to bone and is capable of withstanding tension. Tendons are similar to ligaments and fasciae as they are all made of collagen except that ligaments join one bone to another bone, and fasciae connect muscles to other...

 and ligament
Ligament
In anatomy, the term ligament is used to denote any of three types of structures. Most commonly, it refers to fibrous tissue that connects bones to other bones and is also known as articular ligament, articular larua, fibrous ligament, or true ligament.Ligament can also refer to:* Peritoneal...

 damage, osteoarthritis
Osteoarthritis
Osteoarthritis also known as degenerative arthritis or degenerative joint disease, is a group of mechanical abnormalities involving degradation of joints, including articular cartilage and subchondral bone. Symptoms may include joint pain, tenderness, stiffness, locking, and sometimes an effusion...

, osteochondrosis
Osteochondrosis
Osteochondrosis is a family of orthopedic diseases of the joint that occur in children and adolescents and in rapidly growing animals, particularly pigs, horses, and dogs. They are characterized by interruption of the blood supply of a bone, in particular to the epiphysis, followed by localized...

 and muscular dystrophy
Muscular dystrophy
Muscular dystrophy is a group of muscle diseases that weaken the musculoskeletal system and hamper locomotion. Muscular dystrophies are characterized by progressive skeletal muscle weakness, defects in muscle proteins, and the death of muscle cells and tissue.In the 1860s, descriptions of boys who...

 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

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. Because mesenchymal stem cells can differentiate into the cells that make up bone, cartilage, tendons, and ligaments (as well as muscle, fat, and possibly other tissues), they have been the main type of stem cells studied in the treatment of diseases affecting these tissues. Mesenchymal stem cells are primarily derived from adipose tissue
Adipose tissue
In histology, adipose tissue or body fat or fat depot or just fat is loose connective tissue composed of adipocytes. It is technically composed of roughly only 80% fat; fat in its solitary state exists in the liver and muscles. Adipose tissue is derived from lipoblasts...

 or bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...

. Since an elevated immune response following cell transplantation may result in rejection of exogenous cells (except in the case of cells derived from a very closely genetically related individual), mesenchymal stem cells are often derived from the patient prior to injection in a process known as autologous transplantation. Surgical repair of bone fractures in dogs and sheep has demonstrated that engraftment of mesenchymal stem cells derived from a genetically different donor within the same species, termed allogeneic transplantation, does not elicit an immunological response in the recipient animal and can mediate regeneration of bone tissue in major bony fractures and defects. Stem cells can speed up bone repair in fractures/defects that would normally require extensive grafting, suggesting that mesenchymal stem cell use may provide a useful alternative to conventional grafting techniques. Treating tendon and ligament injuries in horses using stem cells, whether derived from adipose tissue or bone-marrow, has support in the veterinary literature. 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 cell
Endothelial progenitor cell
Endothelial progenitor cells are a population of rare cells that circulate in the blood with the ability to differentiate into endothelial cells, the cells that make up the lining of blood vessels. The process by which blood vessels are born de novo from endothelial progenitor cells is known as...

s, that are necessary for tissue growth, 3) supporting tissue remodeling over scar formation, 4) inhibiting apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

, and 5) differentiating into bone, cartilage, tendon, and ligament tissue.

Significance of stem cell microenvironments
The microenvironment into which stem cells are transplanted significantly alters the capacity of engrafted cells for recovery and repair. The microenviroment provides growth factors and other chemical signals that guide appropriate differentiation of transplanted cell populations and direct transplanted cells to sites of trauma or disease. Repair and recovery can then be mediated via three primary mechanisms: 1) formation and/or recruitment of new blood cells to the damaged region; 2) prevention of programed cell death or apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

; and 3) suppression of inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

. 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.

Sources of autologous (patient-derived) stem cells
Autologous stem cells intended for regenerative therapy are generally isolated either from the patient's bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...

 or from adipose tissue
Adipose tissue
In histology, adipose tissue or body fat or fat depot or just fat is loose connective tissue composed of adipocytes. It is technically composed of roughly only 80% fat; fat in its solitary state exists in the liver and muscles. Adipose tissue is derived from lipoblasts...

. 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.

Currently available treatments for horses and dogs suffering from orthopaedic conditions

Autologous or allogeneic stem cells are currently used as an adjunctive therapy in the surgical repair of some types of fractures in dogs and horses. Autologous stem cell-based treatments for ligament
Ligament
In anatomy, the term ligament is used to denote any of three types of structures. Most commonly, it refers to fibrous tissue that connects bones to other bones and is also known as articular ligament, articular larua, fibrous ligament, or true ligament.Ligament can also refer to:* Peritoneal...

 injury, tendon
Tendon
A tendon is a tough band of fibrous connective tissue that usually connects muscle to bone and is capable of withstanding tension. Tendons are similar to ligaments and fasciae as they are all made of collagen except that ligaments join one bone to another bone, and fasciae connect muscles to other...

 injury, osteoarthritis
Osteoarthritis
Osteoarthritis also known as degenerative arthritis or degenerative joint disease, is a group of mechanical abnormalities involving degradation of joints, including articular cartilage and subchondral bone. Symptoms may include joint pain, tenderness, stiffness, locking, and sometimes an effusion...

, osteochondrosis
Osteochondrosis
Osteochondrosis is a family of orthopedic diseases of the joint that occur in children and adolescents and in rapidly growing animals, particularly pigs, horses, and dogs. They are characterized by interruption of the blood supply of a bone, in particular to the epiphysis, followed by localized...

, 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
Osteoarthritis
Osteoarthritis also known as degenerative arthritis or degenerative joint disease, is a group of mechanical abnormalities involving degradation of joints, including articular cartilage and subchondral bone. Symptoms may include joint pain, tenderness, stiffness, locking, and sometimes an effusion...

 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. The efficacy of using stem cells, whether adipose-derived or bone-marrow derived, for treating tendon and ligament injuries in horses has support in the veterinary literature.

Developments in Stem Cell Treatments in Veterinary Internal Medicine

Currently, research is being conducted to develop stem cell treatments for: 1) horses suffering from COPD
Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease , also known as chronic obstructive lung disease , chronic obstructive airway disease , chronic airflow limitation and chronic obstructive respiratory disease , is the co-occurrence of chronic bronchitis and emphysema, a pair of commonly co-existing diseases...

, neurologic disease, and laminitis
Laminitis
Laminitis is a disease that affects the feet of ungulates. It is best known in horses and cattle. Symptoms include lameness, and increased temperature in the hooves...

; and 2) dogs and cats suffering from heart disease, liver disease, kidney disease, neurologic disease, and immune-mediated disorder

Embryonic stem cell controversy

There is widespread controversy over the use of human embryonic stem cell
Embryonic stem cell
Embryonic stem cells are pluripotent stem cells derived from the inner cell mass of the blastocyst, an early-stage embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consist of 50–150 cells...

s. This controversy primarily targets the techniques used to derive new embryonic stem cell line
Stem cell line
A stem cell line is a family of constantly dividing cells, the product of a single group of stem cells. They are obtained from human or animal tissues and can replicate for long periods of time in vitro...

s, which often requires the destruction of the blastocyst
Blastocyst
The blastocyst is a structure formed in the early embryogenesis of mammals, after the formation of the morula. It is a specifically mammalian example of a blastula. It possesses an inner cell mass , or embryoblast, which subsequently forms the embryo, and an outer layer of cells, or trophoblast,...

. Opposition to the use of human embryonic stem cells in research is often based on philosophical, moral or religious objections.

China

Stem cell research and treatment is currently being practiced at a clinical level in the People's Republic of China
People's Republic of China
China , officially the People's Republic of China , is the most populous country in the world, with over 1.3 billion citizens. Located in East Asia, the country covers approximately 9.6 million square kilometres...

. The Ministry of Health of the People's Republic of China has permitted the use of stem cell therapy for conditions beyond those approved of in Western countries such as the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...

, United Kingdom
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...

, and Australia
Australia
Australia , officially the Commonwealth of Australia, is a country in the Southern Hemisphere comprising the mainland of the Australian continent, the island of Tasmania, and numerous smaller islands in the Indian and Pacific Oceans. It is the world's sixth-largest country by total area...

. The Western World has scrutinized China for its failed attempts to meet international documentation standards of these trials and procedures, despite the overwhelmingly positive anecdotal results.

Stem cell therapies provided in China utilize a variety of cell types including umbilical cord stem cells and olfactory ensheathing cells. The stem cells are then expanded in centralized blood banks before being used in stem cell treatments. State-funded companies based in the Shenzhen
Shenzhen
Shenzhen is a major city in the south of Southern China's Guangdong Province, situated immediately north of Hong Kong. The area became China's first—and one of the most successful—Special Economic Zones...

 Hi-Tech Industrial Zone treat the symptoms of numerous disorders with adult stem cell therapy. Hospitals throughout eastern China provide numerous therapies to patients in coordination with the stem cell providers. These companies' therapies are currently focused on the treatment of neurodegenerative and cardiovascular
Cardiovascular disease
Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...

 disorders. The most radical successes of Chinese adult stem cell therapy have been in treating the brain. These therapies administer stem cells directly to the brain to promote greater motor and brain function in patients with Cerebral Palsy, Alzheimer's, and brain injuries. However, retrospective studies have shown that Chinese use of fetal-derived brain tissue in spinal cord injured human subjects were not as promising as once thought: the phenotype and the fate of the transplanted cells, described as olfactory ensheathing cells, were unknown. As well, perioperative morbidity and lack of functional benefit were identified as the most serious clinical shortcomings. Furthermore, the extent of regulatory policy in the use of stem cell therapies in China is unclear. In the absence of a valid clinical trials protocol, and more regulatory oversight, Western regulatory agencies advise patients and physicians to be cautious when selecting Chinese stem cell therapeutic centers.

Mexico

Stem cell treatment is currently being practiced at a clinical level in Mexico. An International Health Department Permit (COFEPRIS) is required. This permit allows the use of stem cell types beyond those approved of in Western countries such as the United States or Europe. Stem cell therapies provided in Mexico utilize patient Adipose, Bone Marrow, or Donor Placenta sources.

South Korea

In 2005, South Korean scientists claimed to have generated stem cells that were tailored to match the recipient.
Each of the 11 new stem cell lines was developed using somatic cell nuclear transfer
Somatic cell nuclear transfer
In genetics and developmental biology, somatic-cell nuclear transfer is a laboratory technique for creating a clonal embryo, using an ovum with a donor nucleus . It can be used in embryonic stem cell research, or, potentially, in regenerative medicine where it is sometimes referred to as...

 (SCNT) technology. The resultant cells were thought to match the genetic material of the recipient, thus suggesting minimal to no cell rejection.

This study, however, was eventually discredited as the primary researcher,Dr. Woo Suk Hwang, admitted to using cells obtained from his research staff. In Dec 2005, claims were put forward that his research had been manipulated to wrongfully indicate positive results. Later that month, these claims were confirmed by an academic panel.

Ukraine

Today, Ukraine is permitted to perform clinical trials of stem cell treatments (Order of the MH of Ukraine № 630 "About carrying out clinical trials of stem cells", 2008) for the treatment of these pathologies: pancreatic necrosis, cirrhosis, hepatitis, burn disease, diabetes, multiple sclerosis, critical lower limb ischemia. The first medical institution granted the right to conduct clinical trials became the "Institute of Cell Therapy"(Kiev).

See also

  • Cardiovascular Cell Therapy Research Network (CCTRN)
    Cardiovascular Cell Therapy Research Network (CCTRN)
    Cardiovascular Cell Therapy Research Network is a network of physicians, scientists, and support staff dedicated to studying stem cell therapy for treating heart disease. The CCTRN is funded by the National Institutes of Health and includes expert researchers with experience in cardiovascular...

  • Fetal tissue implant
    Fetal tissue implant
    Fetal tissue implant or fetal cell therapy is an experimental medical therapy where researchers implant tissue from a fetus to a patient for treatment of disease. In the case of Parkinson's disease, it is hoped that the fetal tissue would produce chemicals, specifically dopamine, which is lacking...

  • Human Stem Cells Institute
    Human Stem Cells Institute
    Human Stem Cells Institute OJSC , Russia’s first public biotech company, was founded in 2003 along with the country’s largest private family cord blood bank, Gemabank. HSCI engages in development, manufacturing and commercialization of cutting-edge products and services in the areas of cell-based,...


External links

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