Traumatic spinal cord injury (SCI) results in direct and indirect damage to neural tissues, which results in motor and sensory dysfunction, dystonia, and pathological reflex that ultimately lead to paraplegia or tetraplegia. A loss of cells, axon regeneration failure, and time-sensitive pathophysiology make tissue repair difficult. Despite various medical developments, there are currently no effective regenerative treatments. Stem cell therapy is a promising treatment for SCI due to its multiple targets and reactivity benefits. The present review focuses on SCI stem cell therapy, including bone marrow mesenchymal stem cells, umbilical mesenchymal stem cells, adipose-derived mesenchymal stem cells, neural stem cells, neural progenitor cells, embryonic stem cells, induced pluripotent stem cells, and extracellular vesicles. Each cell type targets certain features of SCI pathology and shows therapeutic effects via cell replacement, nutritional support, scaffolds, and immunomodulation mechanisms. However, many preclinical studies and a growing number of clinical trials found that single-cell treatments had only limited benefits for SCI. SCI damage is multifaceted, and there is a growing consensus that a combined treatment is needed.

Keywords: AD-MSCs; BM-MSCs; ESCs; EVs; NPCs; NSCs; U-MSCs; iPSCs; spinal cord injury; stem cells.

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Diagnosis

In the emergency room, a doctor may be able to rule out a spinal cord injury by examination, testing for sensory function and movement, and by asking some questions about the accident.

But if the injured person complains of neck pain, isn't fully awake, or has obvious signs of weakness or neurological injury, emergency diagnostic tests may be needed.

These tests can include:

A few days after injury, when some of the swelling might have subsided, your doctor will conduct a more comprehensive neurological exam to determine the level and completeness of your injury. This involves testing your muscle strength and your ability to sense light touch and pinprick sensations.

Unfortunately, there's no way to reverse damage to the spinal cord. But researchers are continually working on new treatments, including prostheses and medications, that might promote nerve cell regeneration or improve the function of the nerves that remain after a spinal cord injury.

In the meantime, spinal cord injury treatment focuses on preventing further injury and empowering people with a spinal cord injury to return to an active and productive life.

Urgent medical attention is critical to minimize the effects of head or neck trauma. Therefore, treatment for a spinal cord injury often begins at the accident scene.

Emergency personnel typically immobilize the spine as gently and quickly as possible using a rigid neck collar and a rigid carrying board, which they use during transport to the hospital.

In the emergency room, doctors focus on:

If you have a spinal cord injury, you'll usually be admitted to the intensive care unit for treatment. You might be transferred to a regional spine injury center that has a team of neurosurgeons, orthopedic surgeons, spinal cord medicine specialists, psychologists, nurses, therapists and social workers with expertise in spinal cord injury.

Medications. Methylprednisolone (Solu-Medrol) given through a vein in the arm (IV) has been used as a treatment option for an acute spinal cord injury in the past. But recent research has shown that the potential side effects, such as blood clots and pneumonia, from using this medication outweigh the benefits.

Because of this, methylprednisolone is no longer recommended for routine use after a spinal cord injury.

After the initial injury or condition stabilizes, doctors turn their attention to preventing secondary problems that may arise, such as deconditioning, muscle contractures, pressure ulcers, bowel and bladder issues, respiratory infections, and blood clots.

The length of your hospital stay will depend on your condition and the medical issues you face. Once you're well enough to participate in therapies and treatment, you might transfer to a rehabilitation facility.

Rehabilitation team members will begin to work with you while you're in the early stages of recovery. Your team might include a physical therapist, an occupational therapist, a rehabilitation nurse, a rehabilitation psychologist, a social worker, a dietitian, a recreation therapist, and a doctor who specializes in physical medicine (physiatrist) or spinal cord injuries.

During the initial stages of rehabilitation, therapists usually emphasize maintaining and strengthening muscle function, redeveloping fine motor skills, and learning ways to adapt to do day-to-day tasks.

You'll be educated on the effects of a spinal cord injury and how to prevent complications, and you'll be given advice on rebuilding your life and increasing your quality of life and independence.

You'll be taught many new skills, and you'll use equipment and technologies that can help you live on your own as much as possible. You'll be encouraged to resume your favorite hobbies, participate in social and fitness activities, and return to school or the workplace.

Medications might be used to manage some of the effects of spinal cord injury. These include medications to control pain and muscle spasticity, as well as medications that can improve bladder control, bowel control and sexual functioning.

Inventive medical devices can help people with a spinal cord injury become more independent and more mobile. These include:

Your doctor might not be able to give you a prognosis right away. Recovery, if it occurs, usually relates to the severity and level of the injury. The fastest rate of recovery is often seen in the first six months, but some people make small improvements for up to 1 to 2 years.

Explore Mayo Clinic studies testing new treatments, interventions and tests as a means to prevent, detect, treat or manage this condition.

An accident that results in paralysis is a life-changing event. Suddenly having a disability can be frightening and confusing, and adapting is no easy task. You'll likely wonder how your spinal cord injury will affect your everyday activities, job, relationships and long-term happiness.

Recovery takes time, but many people who are paralyzed progress to lead productive and fulfilling lives. It's essential to stay motivated and get the support you need.

If you're newly injured, you and your family will likely experience a period of mourning. The grieving process, which is a normal, healthy part of your recovery, is different for everyone.

It's natural and important to grieve the loss of the way you were. But it's also necessary to set new goals and find ways to go forward.

You'll probably have concerns about how your injury will affect your lifestyle, your financial situation and your relationships. Grieving and emotional stress are normal and common.

However, if your grief is affecting your care, causing you to isolate yourself or prompting you to abuse alcohol or other drugs, you might want to talk to a social worker, psychologist or psychiatrist. Or you might find it helpful to join a support group of people with spinal cord injuries.

Talking with others who understand what you're going through can be encouraging, and you might find good advice on adapting areas of your home or work space to better meet your needs. Ask your doctor or rehabilitation specialist if there are support groups in your area.

One of the best ways to regain control of your life is to educate yourself about your injury and your options for gaining more independence. A range of driving equipment and vehicle modifications is available today.

The same is true of home modification products. Ramps, wider doors, special sinks, grab bars and easy-to-turn doorknobs make it possible for you to live more autonomously.

The costs of a spinal cord injury can be overwhelming, but you might be eligible for economic assistance or support services from the state or federal government or from charitable organizations. Your rehabilitation team can help you identify resources in your area.

Some friends and family members might be unsure about how to act around you. Being educated about your spinal cord injury and willing to educate others can benefit all of you.

Explain the effects of your injury and what others can do to help. But don't hesitate to tell friends and loved ones when they're helping too much. Although it may be uncomfortable at first, talking about your injury can strengthen your relationships with family and friends.

Your spinal cord injury might affect your body's sexual responsiveness. However, you're a sexual being with sexual desires. A fulfilling emotional and physical relationship is possible but requires communication, experimentation and patience.

A professional counselor can help you and your partner communicate your needs and feelings. Your doctor can provide the medical information you need regarding sexual health. You can have a satisfying future complete with intimacy and sexual pleasure.

As you learn more about your injury and treatment options, you might be surprised by all you can do. Thanks to new technologies, treatments and devices, people with spinal cord injuries play basketball and participate in track meets. They paint and take photographs. They get married, have and raise children, and have rewarding jobs.

Advances in stem cell research and nerve cell regeneration give hope for greater recovery for people with spinal cord injuries. And new treatments are being investigated for people with long-standing spinal cord injuries.

No one knows when new treatments will be available, but you can remain hopeful about the future of spinal cord research while living your life to the fullest today.

Traumatic spinal cord injuries are emergencies, and people who are injured might not be able to participate in their care at first.

A number of specialists will be involved in stabilizing the condition, including a doctor who specializes in nervous system disorders (neurologist) and a surgeon who specializes in spinal cord injuries and other nervous system problems (neurosurgeon), among others.

A doctor who specializes in spinal cord injuries will lead your rehabilitation team, which will include a variety of specialists.

If you have a possible spinal cord injury or you accompany someone who's had a spinal cord injury and can't provide the necessary information, here are some things you can do.

For a spinal cord injury, some basic questions to ask the doctor include:

Don't hesitate to ask other questions you have.

Your doctor is likely to ask questions, including:

Oct. 02, 2021

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What is a spinal cord injury?What are some signs and symptoms of spinal cord injury?How are spinal cord injuries diagnosed?How is SCI treated?What research is being done?How can I help with research?Where can I get more information?Appendix

A spinal cord injury (SCI) is damage to the tight bundle of cells and nerves that sends and receives signals from the brain to and from the rest of the body. The spinal cord extends from the lower part of the brain down through the lower back.

SCI can be caused by direct injury to the spinal cord itself or from damage to the tissue and bones (vertebrae) that surround the spinal cord. This damage can result in temporary or permanent changes in sensation, movement, strength, and body functions below the site of injury.

Injury and severity

The extent of disability depends on where along the spinal cord the injury occurs and the severity of the injury.

Loss of nerve function occurs below the level of injury. An injury higher on the spinal cord can cause paralysis in most of the body and affect all limbs (called tetraplegia or quadriplegia). A lower injury to the spinal cord may cause paralysis affecting the legs and lower body (called paraplegia).

A spinal cord injury can damage a few, many, or almost all of the nerve fibers that cross the site of injury. A variety of cells located in and around the injury site may also die. Some injuries having little or no nerve cell death may allow an almost complete recovery.

Type of injury

A spinal cord injury can be classified as complete or incomplete.

Primary damage is immediate and is caused directly by the injury. Secondary damage results from inflammation and swelling that can press on the spinal cord and vertebrae, as well as from changes in the activity of cells and cell death.

Common causes

Motor vehicle accidents and catastrophic falls are the most common causes of SCI in the United States. The rest are due to acts of violence (primarily gunshot wounds and assaults), sports injuries, medical or surgical injury, industrial accidents, diseases and conditions that can damage the spinal cord, and other less common causes.

For information on what makes up the spinal cord and spinal column, see the Appendix at the end of this document.

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A spinal cord injury can cause one or more symptoms including:

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How are spinal cord injuries diagnosed?

The emergency room physician will check for movement or sensation at or below the level of injury, as well as proper breathing, responsiveness, and weakness. Emergency medical tests for a spinal cord injury include:

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Immediate (acute) treatment

At the accident scene, emergency personnel will put a rigid collar around the neck and carefully place the person on a rigid backboard to prevent further damage to the spinal cord. Sometimes the person may be sedated to relax and prevent movement. A breathing tube may be inserted if the person has problems breathing and the body isnt receiving enough oxygen from the lungs.

Immediate treatment at the trauma center may include:

Possible Complications of SCI and treatment

Once someone has survived the injury and begins to cope psychologically and emotionally, the next concern is how to live with disabilities. Doctors are now able to predict with reasonable accuracy the likely long-term outcome of spinal cord injuries. This helps people experiencing SCI set achievable goals for themselves and gives families and loved ones a realistic set of expectations for the future.

Rehabilitation

Rehabilitation programs combine physical therapies with skill-building activities and counseling to provide social and emotional support, as well as to increase independence and quality of life.

A rehabilitation team is usually led by a doctor specializing in physical medicine and rehabilitation (called a physiatrist) and often includes social workers, physical and occupational therapists, recreational therapists, rehabilitation nurses, rehabilitation psychologists, vocational counselors, nutritionists, a case worker, and other specialists.

In the initial phase of rehabilitation, therapists emphasize regaining communication skills and leg and arm strength. For some individuals, mobility will only be possible with assistive devices such as a walker, leg braces, or a wheelchair. Communication skills such as writing, typing, and using the telephone may also require adaptive devices for some people with tetraplegia.

Adaptive devices also may help people with spinal cord injury to regain independence and improve mobility and quality of life. Such devices may include a wheelchair, electronic stimulators, assisted training with walking,neural prostheses (assistive devices that may stimulate the nerves to restore lost functions), computer adaptations, and other computer-assisted technology.

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Scientists continue to investigate new ways to better understand and treat spinal cord injuries.

Much of this research is conducted or funded by the National Institute of Neurological Disorders and Stroke (NINDS). NINDS is a component of the National Institutes of Health (NIH), the leading supporter of biomedical research in the world. Other NIH components, as well as the Department of Veterans Affairs, other Federal agencies, research institutions, and voluntary health organizations, also fund and conduct basic to clinical research related to improvement of function in paralyzed individuals.

The Brain Research through Advancing Innovative Technologies (BRAIN) Initiative brings together multiple federal agencies and private organizations to develop and apply new technologies to understand how complex circuits of nerve cells enable thinking, movement control, and perception. Research funded as part of the BRAIN Initiative that has the potential to improve the outlook for SCI includes:

Basic spinal cord function research studies how the normal spinal cord develops, processes sensory information, controls movement, and generates rhythmic patterns (like walking and breathing). Basic studies using cells and animal models provide an essential foundation for developing interventions for spinal cord injury.

Research on injury mechanisms focuses on what causes immediate harm and on the cascade of helpful and harmful bodily reactions that protect from or contribute to damage in the hours and days following a spinal cord injury. This includes testing of neuroprotective interventions in laboratory animals.

Current research on SCI is focused on advancing our understanding of four key principles of spinal cord repair:

Neural engineering strategies build on decades of pioneering NINDS investment that established the field of neural prostheses. For example, researchers are developing a networked functional electrical stimulation system to restore independence through combined implants for hand function, postural control, and bowel and bladder control. NINDS has also led development of experimental brain computer interfaces that enable people to control a computer cursor or robotic arm directly from their brains.

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Clinical research uses human volunteersboth those who are healthy or may have an illness or diseaseto help researchers learn more about a disorder and perhaps find better ways to safely detect, treat, or prevent disease. For information about finding and participating in clinical research visit NIH Clinical Research Trials and You at http://www.nih.gov/health/clinicaltrials. Use search terms such as spinal cord injury and tetraplegia to access current and completed trials involving spinal injury.

Other centers maintain registries of people interested in participating in ongoing or future clinical research studies. A multi-site network supported by the Christopher and Dana Reeve Foundation called the NeuroRecovery Network also accepts volunteer research participants. For more information, see http://www.christopherreeve.org/site/c.ddJFKRNoFiG/b.5399929/k.6F37/NeuroRecovery_Network.htm.

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For more information on neurological disorders or research programs funded by the National Institute of Neurological Disorders and Stroke, contact the Institute's Brain Resources and Information Network (BRAIN) at:

BRAINP.O. Box 5801Bethesda, MD 20824800-352-9424

Information also is available from the following organizations:

Christopher and Dana Reeve Foundation Email: Information@christopherreeve.org 973-379-2690 or 800-225-0292

Miami Project to Cure ParalysisEmail: miamiproject@miami.edu 305-243-6001 or 800-782-6387

National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) 202-401-4634; 202-245-7316 (TTY)

National Rehabilitation Information Center (NARIC) Landover, MD 20785301-459-5900; 800-346-2742; 301-459-5984 (TTY)

Paralyzed Veterans of America (PVA) Email: info@pva.orr 800-424-8200

United Spinal Association Email: askus@unitedspinal.org 718-803-3782 or 800-962-9629

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Anatomy of the spinal cord

The spinal cord is a soft, cylindrical column of tightly bundled nerve cells (neurons and glia), nerve fibers that transmit nerve signals (called axons), and blood vessels. It sends and receives information between the brain and the rest of the body. Millions of nerve cells situated in the spinal cord itself also coordinate complex patterns of movements such as rhythmic breathing and walking.

The spinal cord extends from the brain to the lower back through a canal in the center of the bones of the spine. Like the brain, the spinal cord is protected by three layers of tissue and is surrounded by the cerebrospinal fluid that acts as a cushion against shock or injury.

Inside the spinal cord is:

Other types of nerve cells sit just outside the spinal cord and relay information to the brain.

31 pairs of nerves, each of which contains thousands of axons, are divided into 4 regions having individual segments and link the spinal cord to muscles and other parts of the body:

The spinal column, which surrounds and protects the spinal cord, is made up of 33 rings of bone (called vertebrae), pads of semi-rigid cartilage (called discs), and narrow spaces called foramen that act as passages for spinal nerves to travel to and from the rest of the body. These are places where the spinal cord is particularly vulnerable to direct injury.

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"Spinal Cord Injury: Hope Through Research", NINDS, Publication date July 2013.

NIH Publication 13-NS-160

Back toSpinal Cord Injury Information Page

See a list of all NINDS Disorders

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Prepared by:Office of Communications and Public LiaisonNational Institute of Neurological Disorders and StrokeNational Institutes of HealthBethesda, MD 20892

NINDS health-related material is provided for information purposes only and does not necessarily represent endorsement by or an official position of the National Institute of Neurological Disorders and Stroke or any other Federal agency. Advice on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined that patient or is familiar with that patient's medical history.

All NINDS-prepared information is in the public domain and may be freely copied. Credit to the NINDS or the NIH is appreciated.

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Ethical controversy over the use of embryonic stem cells

The stem cell controversy is the consideration of the ethics of research involving the development and use of human embryos. Most commonly, this controversy focuses on embryonic stem cells. Not all stem cell research involves human embryos. For example, adult stem cells, amniotic stem cells, and induced pluripotent stem cells do not involve creating, using, or destroying human embryos, and thus are minimally, if at all, controversial. Many less controversial sources of acquiring stem cells include using cells from the umbilical cord, breast milk, and bone marrow, which are not pluripotent.

For many decades, stem cells have played an important role in medical research, beginning in 1868 when Ernst Haeckel first used the phrase to describe the fertilized egg which eventually gestates into an organism. The term was later used in 1886 by William Sedgwick to describe the parts of a plant that grow and regenerate. Further work by Alexander Maximow and Leroy Stevens introduced the concept that stem cells are pluripotent. This significant discovery led to the first human bone marrow transplant by E. Donnall Thomas in 1956, which although successful in saving lives, has generated much controversy since. This has included the many complications inherent in stem cell transplantation (almost 200 allogeneic marrow transplants were performed in humans, with no long-term successes before the first successful treatment was made), through to more modern problems, such as how many cells are sufficient for engraftment of various types of hematopoietic stem cell transplants, whether older patients should undergo transplant therapy, and the role of irradiation-based therapies in preparation for transplantation.

The discovery of adult stem cells led scientists to develop an interest in the role of embryonic stem cells, and in separate studies in 1981 Gail Martin and Martin Evans derived pluripotent stem cells from the embryos of mice for the first time. This paved the way for Mario Capecchi, Martin Evans, and Oliver Smithies to create the first knockout mouse, ushering in a whole new era of research on human disease. In 1995 adult stem cell research with human use was patented (US PTO with effect from 1995). In fact, human use was published in World J Surg 1991 & 1999 (B G Matapurkar). Salhan, Sudha (August 2011).[1]

In 1998, James Thomson and Jeffrey Jones derived the first human embryonic stem cells, with even greater potential for drug discovery and therapeutic transplantation. However, the use of the technique on human embryos led to more widespread controversy as criticism of the technique now began from the wider public who debated the moral ethics of questions concerning research involving human embryonic cells.

Since pluripotent stem cells have the ability to differentiate into any type of cell, they are used in the development of medical treatments for a wide range of conditions.[2] Treatments that have been proposed include treatment for physical trauma, degenerative conditions, and genetic diseases (in combination with gene therapy). Yet further treatments using stem cells could potentially be developed due to their ability to repair extensive tissue damage.[3]

Great levels of success and potential have been realized from research using adult stem cells. In early 2009, the FDA approved the first human clinical trials using embryonic stem cells. Only cells from an embryo at the morula stage or earlier are truly totipotent, meaning that they are able to form all cell types including placental cells. Adult stem cells are generally limited to differentiating into different cell types of their tissue of origin. However, some evidence suggests that adult stem cell plasticity may exist, increasing the number of cell types a given adult stem cell can become.

Destruction of a human embryo is required in order to research new embryonic cell lines. Much of the debate surrounding human embryonic stem cells, therefore, concern ethical and legal quandaries around the destruction of an embryo. Ethical and legal questions such as "At what point does one consider life to begin?" and "Is it just to destroy a human embryo if it has the potential to cure countless numbers of patients and further our understanding of disease?" are central to the controversy. Political leaders debate how to regulate and fund research studies that involve the techniques used to remove the embryo cells. No clear consensus has emerged.[4]

Much of the criticism has been a result of religious beliefs and, in the most high-profile case, US President George W Bush signed an executive order banning the use of federal funding for any stem cell lines other than those already in existence, stating at the time, "My position on these issues is shaped by deeply held beliefs," and "I also believe human life is a sacred gift from our creator."[5] This ban was in part revoked by his successor Barack Obama, who stated: "As a person of faith, I believe we are called to care for each other and work to ease human suffering. I believe we have been given the capacity and will to pursue this research and the humanity and conscience to do so responsibly."[6]

Some stem cell researchers are working to develop techniques of isolating stem cells with similar potency as embryonic stem cells, but do not require the destruction of a human embryo.

Foremost among these was the discovery in August 2006 that human adult somatic cells can be cultured in vitro with the four Yamanaka factors (Oct-4, SOX2, c-Myc, KLF4) which effectively returns a cell to the pluripotent state similar to that observed in embryonic stem cells.[7][8] This major breakthrough won a Nobel Prize for the discoverers, Shinya Yamanaka and John Gurdon.[9] Induced pluripotent stem cells are those derived from adult somatic cells and have the potential to provide an alternative for stem cell research that does not require the destruction of human embryos. Some debate remains about the similarities of these cells to embryonic stem cells as research has shown that the induced pluripotent cells may have a different epigenetic memory or modifications to the genome than embryonic stem cells depending on the tissue of origin and donor the iPSCs come from.[10] While this may be the case, epigenetic manipulation of the cells is possible using small molecules and more importantly, iPSCs from multiple tissues of origin have been shown to give rise to a viable organism similar to the way ESCs can.[11] This allows iPSCs to serve as a powerful tool for tissue generation, drug screening, disease modeling, and personalized medicine that has far fewer ethical considerations than embryonic stem cells that would otherwise serve the same purpose.

In an alternative technique, researchers at Harvard University, led by Kevin Eggan and Savitri Marajh, have transferred the nucleus of a somatic cell into an existing embryonic stem cell, thus creating a new stem cell line.[12] This technique known as somatic cell nuclear transfer (SCNT) creates pluripotent cells that are genetically identical to the donor.[13] While the creation of stem cells via SCNT does not destroy an embryo, it requires an oocyte from a donor which opens the door to a whole new set of ethical considerations such as the debate as to whether or not it is appropriate to offer financial incentives to female donors.[14]

Researchers at Advanced Cell Technology, led by Robert Lanza and Travis Wahl, reported the successful derivation of a stem cell line using a process similar to preimplantation genetic diagnosis, in which a single blastomere is extracted from a blastocyst.[15] At the 2007 meeting of the International Society for Stem Cell Research (ISSCR),[16] Lanza announced that his team had succeeded in producing three new stem cell lines without destroying the parent embryos.[17]"These are the first human embryonic cell lines in existence that didn't result from the destruction of an embryo." Lanza is currently in discussions with the National Institutes of Health to determine whether the new technique sidesteps U.S. restrictions on federal funding for ES cell research.[18]

Anthony Atala of Wake Forest University says that the fluid surrounding the fetus has been found to contain stem cells that, when used correctly, "can be differentiated towards cell types such as fat, bone, muscle, blood vessel, nerve and liver cells." The extraction of this fluid is not thought to harm the fetus in any way. He hopes "that these cells will provide a valuable resource for tissue repair and for engineered organs, as well."[19] AFSCs have been found to express both embryonic and adult stem cell markers as well as having the ability to be maintained over 250 population doublings.[20]

Similarly, pro-life supporters claim that the use of adult stem cells from sources such as the cord blood has consistently produced more promising results than the use of embryonic stem cells.[21] Research has shown that umbilical cord blood (UCB) is in fact a viable source for stem cells and their progenitors which occur in high frequencies within the fluid. Furthermore, these cells may hold an advantage over induced PSC as they can create large quantities of homogenous cells.[22]

IPSCs and other embryonic stem cell alternatives must still be collected and maintained with the informed consent of the donor as a donor's genetic information is still within the cells and by the definition of pluripotency, each alternative cell type has the potential to give rise to viable organisms. Generation of viable offspring using iPSCs has been shown in mouse models through tetraploid complementation.[23][24] This potential for the generation of viable organisms and the fact that iPSC cells contain the DNA of donors require that they be handled along the ethical guidelines laid out by the food and drug administration (FDA), European Medicines Agency (EMA), and International Society for Stem Cell Research (ISSCR).

Stem cell debates have motivated and reinvigorated the anti-abortion movement, whose members are concerned with the rights and status of the human embryo as an early-aged human life. They believe that embryonic stem cell research profits from and violates the sanctity of life and is tantamount to murder.[25] The fundamental assertion of those who oppose embryonic stem cell research is the belief that human life is inviolable, combined with the belief that human life begins when a sperm cell fertilizes an egg cell to form a single cell. The view of those in favor is that these embryos would otherwise be discarded, and if used as stem cells, they can survive as a part of a living human person.

A portion of stem cell researchers use embryos that were created but not used in in vitro fertility treatments to derive new stem cell lines. Most of these embryos are to be destroyed, or stored for long periods of time, long past their viable storage life. In the United States alone, an estimated at least 400,000 such embryos exist.[26] This has led some opponents of abortion, such as Senator Orrin Hatch, to support human embryonic stem cell research.[27] See also embryo donation.

Medical researchers widely report that stem cell research has the potential to dramatically alter approaches to understanding and treating diseases, and to alleviate suffering. In the future, most medical researchers anticipate being able to use technologies derived from stem cell research to treat a variety of diseases and impairments. Spinal cord injuries and Parkinson's disease are two examples that have been championed by high-profile media personalities (for instance, Christopher Reeve and Michael J. Fox, who have lived with these conditions, respectively). The anticipated medical benefits of stem cell research add urgency to the debates, which has been appealed to by proponents of embryonic stem cell research.

In August 2000, The U.S. National Institutes of Health's Guidelines stated:

... research involving human pluripotent stem cells ... promises new treatments and possible cures for many debilitating diseases and injuries, including Parkinson's disease, diabetes, heart disease, multiple sclerosis, burns and spinal cord injuries. The NIH believes the potential medical benefits of human pluripotent stem cell technology are compelling and worthy of pursuit in accordance with appropriate ethical standards.[28]

In 2006, researchers at Advanced Cell Technology of Worcester, Massachusetts, succeeded in obtaining stem cells from mouse embryos without destroying the embryos.[29] If this technique and its reliability are improved, it would alleviate some of the ethical concerns related to embryonic stem cell research.

Another technique announced in 2007 may also defuse the longstanding debate and controversy. Research teams in the United States and Japan have developed a simple and cost-effective method of reprogramming human skin cells to function much like embryonic stem cells by introducing artificial viruses. While extracting and cloning stem cells is complex and extremely expensive, the newly discovered method of reprogramming cells is much cheaper. However, the technique may disrupt the DNA in the new stem cells, resulting in damaged and cancerous tissue. More research will be required before noncancerous stem cells can be created.[30][31][32][33]

Update of article to include 2009/2010 current stem cell usages in clinical trials:[34][35] The planned treatment trials will focus on the effects of oral lithium on neurological function in people with chronic spinal cord injury and those who have received umbilical cord blood mononuclear cell transplants to the spinal cord. The interest in these two treatments derives from recent reports indicating that umbilical cord blood stem cells may be beneficial for spinal cord injury and that lithium may promote regeneration and recovery of function after spinal cord injury. Both lithium and umbilical cord blood are widely available therapies that have long been used to treat diseases in humans.

This argument often goes hand-in-hand with the utilitarian argument, and can be presented in several forms:

This is usually presented as a counter-argument to using adult stem cells, as an alternative that does not involve embryonic destruction.

Adult stem cells have provided many different therapies for illnesses such as Parkinson's disease, leukemia, multiple sclerosis, lupus, sickle-cell anemia, and heart damage[43] (to date, embryonic stem cells have also been used in treatment),[44] Moreover, there have been many advances in adult stem cell research, including a recent study where pluripotent adult stem cells were manufactured from differentiated fibroblast by the addition of specific transcription factors.[45] Newly created stem cells were developed into an embryo and were integrated into newborn mouse tissues, analogous to the properties of embryonic stem cells.

Austria, Denmark, France, Germany, Portugal and Ireland do not allow the production of embryonic stem cell lines,[46] but the creation of embryonic stem cell lines is permitted in Finland, Greece, the Netherlands, Sweden, and the United Kingdom.[46]

In 1973, Roe v. Wade legalized abortion in the United States. Five years later, the first successful human in vitro fertilization resulted in the birth of Louise Brown in England. These developments prompted the federal government to create regulations barring the use of federal funds for research that experimented on human embryos. In 1995, the NIH Human Embryo Research Panel advised the administration of President Bill Clinton to permit federal funding for research on embryos left over from in vitro fertility treatments and also recommended federal funding of research on embryos specifically created for experimentation. In response to the panel's recommendations, the Clinton administration, citing moral and ethical concerns, declined to fund research on embryos created solely for research purposes,[47] but did agree to fund research on leftover embryos created by in vitro fertility treatments. At this point, the Congress intervened and passed the 1995 DickeyWicker Amendment (the final bill, which included the Dickey-Wicker Amendment, was signed into law by Bill Clinton) which prohibited any federal funding for the Department of Health and Human Services be used for research that resulted in the destruction of an embryo regardless of the source of that embryo.

In 1998, privately funded research led to the breakthrough discovery of human embryonic stem cells (hESC).[48] This prompted the Clinton administration to re-examine guidelines for federal funding of embryonic research. In 1999, the president's National Bioethics Advisory Commission recommended that hESC harvested from embryos discarded after in vitro fertility treatments, but not from embryos created expressly for experimentation, be eligible for federal funding. Though embryo destruction had been inevitable in the process of harvesting hESC in the past (this is no longer the case[49][50][51][52]), the Clinton administration had decided that it would be permissible under the Dickey-Wicker Amendment to fund hESC research as long as such research did not itself directly cause the destruction of an embryo. Therefore, HHS issued its proposed regulation concerning hESC funding in 2001. Enactment of the new guidelines was delayed by the incoming George W. Bush administration which decided to reconsider the issue.

President Bush announced, on August 9, 2001, that federal funds, for the first time, would be made available for hESC research on currently existing embryonic stem cell lines. President Bush authorized research on existing human embryonic stem cell lines, not on human embryos under a specific, unrealistic timeline in which the stem cell lines must have been developed. However, the Bush Administration chose not to permit taxpayer funding for research on hESC cell lines not currently in existence, thus limiting federal funding to research in which "the life-and-death decision has already been made."[53] The Bush Administration's guidelines differ from the Clinton Administration guidelines which did not distinguish between currently existing and not-yet-existing hESC. Both the Bush and Clinton guidelines agree that the federal government should not fund hESC research that directly destroys embryos.

Neither Congress nor any administration has ever prohibited private funding of embryonic research. Public and private funding of research on adult and cord blood stem cells is unrestricted.

In April 2004, 206 members of Congress signed a letter urging President Bush to expand federal funding of embryonic stem cell research beyond what Bush had already supported.

In May 2005, the House of Representatives voted 238194 to loosen the limitations on federally funded embryonic stem-cell research by allowing government-funded research on surplus frozen embryos from in vitro fertilization clinics to be used for stem cell research with the permission of donors despite Bush's promise to veto the bill if passed.[54] On July 29, 2005, Senate Majority Leader William H. Frist (R-TN) announced that he too favored loosening restrictions on federal funding of embryonic stem cell research.[55] On July 18, 2006, the Senate passed three different bills concerning stem cell research. The Senate passed the first bill (the Stem Cell Research Enhancement Act) 6337, which would have made it legal for the federal government to spend federal money on embryonic stem cell research that uses embryos left over from in vitro fertilization procedures.[56] On July 19, 2006, President Bush vetoed this bill. The second bill makes it illegal to create, grow, and abort fetuses for research purposes. The third bill would encourage research that would isolate pluripotent, i.e., embryonic-like, stem cells without the destruction of human embryos.

In 2005 and 2007, Congressman Ron Paul introduced the Cures Can Be Found Act,[57] with 10 cosponsors. With an income tax credit, the bill favors research upon non-embryonic stem cells obtained from placentas, umbilical cord blood, amniotic fluid, humans after birth, or unborn human offspring who died of natural causes; the bill was referred to committee. Paul argued that hESC research is outside of federal jurisdiction either to ban or to subsidize.[58]

Bush vetoed another bill, the Stem Cell Research Enhancement Act of 2007,[59] which would have amended the Public Health Service Act to provide for human embryonic stem cell research. The bill passed the Senate on April 11 by a vote of 6334, then passed the House on June 7 by a vote of 247176. President Bush vetoed the bill on July 19, 2007.[60]

On March 9, 2009, President Obama removed the restriction on federal funding for newer stem cell lines.[61] Two days after Obama removed the restriction, the president then signed the Omnibus Appropriations Act of 2009, which still contained the long-standing DickeyWicker Amendment which bans federal funding of "research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death;"[62] the Congressional provision effectively prevents federal funding being used to create new stem cell lines by many of the known methods. So, while scientists might not be free to create new lines with federal funding, President Obama's policy allows the potential of applying for such funding into research involving the hundreds of existing stem cell lines as well as any further lines created using private funds or state-level funding. The ability to apply for federal funding for stem cell lines created in the private sector is a significant expansion of options over the limits imposed by President Bush, who restricted funding to the 21 viable stem cell lines that were created before he announced his decision in 2001.[63]The ethical concerns raised during Clinton's time in office continue to restrict hESC research and dozens of stem cell lines have been excluded from funding, now by judgment of an administrative office rather than presidential or legislative discretion.[64]

In 2005, the NIH funded $607 million worth of stem cell research, of which $39 million was specifically used for hESC.[65] Sigrid Fry-Revere has argued that private organizations, not the federal government, should provide funding for stem-cell research, so that shifts in public opinion and government policy would not bring valuable scientific research to a grinding halt.[66]

In 2005, the State of California took out $3 billion in bond loans to fund embryonic stem cell research in that state.[67]

China has one of the most permissive human embryonic stem cell policies in the world. In the absence of a public controversy, human embryo stem cell research is supported by policies that allow the use of human embryos and therapeutic cloning.[68]

Generally speaking, no group advocates for unrestricted stem cell research, especially in the context of embryonic stem cell research.

According to Rabbi Levi Yitzchak Halperin of the Institute for Science and Jewish Law in Jerusalem, embryonic stem cell research is permitted so long as it has not been implanted in the womb. Not only is it permitted, but research is encouraged, rather than wasting it.

As long as it has not been implanted in the womb and it is still a frozen fertilized egg, it does not have the status of an embryo at all and there is no prohibition to destroy it...

However in order to remove all doubt [as to the permissibility of destroying it], it is preferable not to destroy the pre-embryo unless it will otherwise not be implanted in the woman who gave the eggs (either because there are many fertilized eggs, or because one of the parties refuses to go on with the procedure the husband or wife or for any other reason). Certainly it should not be implanted into another woman.... The best and worthiest solution is to use it for life-saving purposes, such as for the treatment of people that suffered trauma to their nervous system, etc.

Rabbi Levi Yitzchak Halperin, Ma'aseh Choshev vol. 3, 2:6

Similarly, the sole Jewish majority state, Israel, permits research on embryonic stem cells.

The Catholic Church opposes human embryonic stem cell research calling it "an absolutely unacceptable act." The Church supports research that involves stem cells from adult tissues and the umbilical cord, as it "involves no harm to human beings at any state of development."[69] This support has been expressed both politically and financially, with different Catholic groups either raising money indirectly, offering grants, or seeking to pass federal legislation, according to the United States Conference of Catholic Bishops. Specific examples include a grant from the Catholic Archiocese of Sydney which funded research demonstrating the capabilities of adult stem cells, and the U.S. Conference of Catholic Bishops working to pass federal legislation creating a nationwide public bank for umbilical cord blood stem cells.[70]

The Southern Baptist Convention opposes human embryonic stem cell research on the grounds that the "Bible teaches that human beings are made in the image and likeness of God (Gen. 1:27; 9:6) and protectable human life begins at fertilization."[71] However, it supports adult stem cell research as it does "not require the destruction of embryos."[71]

The United Methodist Church opposes human embryonic stem cell research, saying, "a human embryo, even at its earliest stages, commands our reverence."[72] However, it supports adult stem cell research, stating that there are "few moral questions" raised by this issue.[72]

The Assemblies of God opposes human embryonic stem cell research, saying, it "perpetuates the evil of abortion and should be prohibited."[73]

Islamic scholars generally favor the stance that scientific research and development of stem cells is allowed as long as it benefits society while causing the least amount of harm to the subjects. "Stem cell research is one of the most controversial topics of our time period and has raised many religious and ethical questions regarding the research being done. With there being no true guidelines set forth in the Qur'an against the study of biomedical testing, Muslims have adopted any new studies as long as the studies do not contradict another teaching in the Qur'an. One of the teachings of the Qur'an states that 'Whosoever saves the life of one, it shall be if he saves the life of humankind' (5:32), it is this teaching that makes stem cell research acceptable in the Muslim faith because of its promise of potential medical breakthrough."[74] This statement does not, however, make a distinction between adult, embryonic, or stem-cells. In specific instances, different sources have issued fatwas, or nonbinding but authoritative legal opinions according to Islamic faith, ruling on conduct in stem cell research. The Fatwa of the Islamic Jurisprudence Council of the Islamic World League (December 2003) addressed permissible stem cell sources, as did the Fatwa Khomenei (2002) in Iran. Several different governments in predominantly Muslim countries have also supported stem cell research, notably Saudi Arabia and Iran.

The First Presidency of The Church of Jesus Christ of Latter-day Saints "has not taken a position regarding the use of embryonic stem cells for research purposes. The absence of a position should not be interpreted as support for or opposition to any other statement made by Church members, whether they are for or against embryonic stem cell research.[75]

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Stem cell controversy - Wikipedia

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How are new treatments developed?

If you have seen a stem cell treatment advertised, featured in the media, or mentioned to you by a friend or fellow patient, it can be hard to work out if it may be an option for you.

Although there is a lot of attention surrounding the potential of stem cells, in reality, the range of diseases for which there are current proven stem cell treatments is quite small. Within Australia the only proven treatments available involving stem cells are corneal and skin grafting, and blood stem cell transplants for the treatment of some blood disorders, inherited immune and metabolic disorders, cancer and autoimmune diseases. There are many other potential treatments, but these are still in the research phase or in clinical trials and are yet to be proven as safe and effective.

This page provides a breakdown of the steps that should occur before a stem cell treatment makes it to you in a clinic, and identifies who should be looking after your interests.

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Stem Cells Australia | Australian research, stem cell treatments and ...

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Replacing retinal pigment epithelial cells

Retinal pigment epithelial (RPE) cells have a number of important jobs, including looking after the adjacent retina. If these cells stop working properly due to damage or disease, then certain parts of the retina die. As the retina is the component of the eye responsible for detecting light, this leads to the onset of blindness. RPE cells can be damaged in a variety of diseases such as: age-related macular degeneration (AMD), retinitis pigmentosa and Lebers congenital aneurosis.

One way to treat these diseases would be to replace the damaged RPE cells with transplanted healthy cells. Unfortunately, it is not possible to take healthy RPE cells from donors so it is necessary to find another source of cells for transplantation. Scientists have recently produced new RPE cells from both embryonic stem cells and iPS cells in the lab. The safety of embryonic stem cell-derived RPE cells has been tested in phase I/II clinical trials for patients with Stargardts macular dystrophy, and for thse affected by AMD by a stem cell biotech company called Advanced Cell Technologies. Theresults of the trial, published in 2014, demonstrated safety and showed engraftment of the transplanted RPE cells. However, some participants experienced adverse side effects from the immunosuppression and the transplantation procedure itself. Interestingly, despite not being an endpoint of this trial, several patients also reported an improvement in vision.

A second Phase I/II trial exploringthe use of RPEs derived from human embryonic stem cells for people with wet AMDis currently underway in the United Kingdom. The first patient received their transplant in September 2015. This work, led by Prof Pete Coffey, is ongoing and is being carried out at Moorfields Eye Hospital as part of the London Project to Cure Blindness.

Finally, Japanese researcher, Dr Masayo Takahashi is leading a clinical trial in Japan which transplants RPE cells made from iPS cells into patients with wet AMD. The trial was put on hold for several months due to regulatory changes in Japan and concerns about mutations in an iPS cell product to be used in the trial. The trial has recommenced June 2016 and many await the results.

There areseveral other phase I or I/II clinical trials using pluripotent stem cells world-wideinvolving small numbers of participants. These trials are examining primarily the safety, but in some cases also the effectiveness, of the use of RPEs developed from pluripotent stem cells in dry and wet AMD and Stargardts macular degeneration.

Replacement of damaged RPE cells will only be effective in patients who still have at least part of a working retina, and therefore some level of vision (i.e. at early stages of the disease). This is because the RPE cells are not themselves responsible for seeing, but are actually responsible for supporting the seeing retina. Sight is lost in these types of diseases when the retina begins to degenerate because the RPE cells are not doing their job properly. So the RPE cells need to be replaced in time for them to support a retina that is still working. It is hoped that transplantation of new RPE cells will then permanently halt further loss of vision, and in some cases may even improve vision to some degree.

Replacing retinal pigment epithelial cells:Techniques for growing cells for therapies are being researched and tested in early clinical safety trials.

Replacing retinal cells

In many of the cases where vision is lost, we often find that the problem lies with malfunctioning retinal circuitry. Different disorders occur when particular, specialized cells in the circuit either stop working properly or die off. Despite the retina being more complicated than other components of the eye, it is hoped that if a source of new retinal cells can be found, we may be able to replace the damaged or dying cells to repair the retina. In addition, this approach may also help to repair damage caused to the optic nerve.

Again, scientists have turned to stem cell technology to provide the source of replacement cells. Several studies have now reported that both embryonic stem cells and iPS cells can be turned into different types of retinal cells in the lab. Within the eye, a type of cell called the Mller cell, which is found in the retina, is known to act as a stem cell in some species, such as the zebra fish. It has been suggested that this cell may also be able to act as a stem cell in humans, in which case it may provide another source of retinal cells for repair of the retina.

Unlike RPE cell transplantation, direct repair of the retina may allow patients who have already lost their vision to have it restored to some degree. This gives hope for patients with disorders like late-stage age-related macular degeneration, where the light-sensitive photoreceptor cells in the retina have already been lost. This type of research may also provide new treatments for people who suffer from retinal diseases like retinitis pigmentosa and glaucoma. However, despite encouraging evidence, such research is very much in its infancy. There are currently no patient clinical trials planned using this type of approach, as significant further research is still required first.

Replacing the nerve cells of the retina:Current research aims to understand how to produce retinal nerve cells that could be used in future therapies.

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The eye and stem cells: the path to treating blindness

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(SACRAMENTO)

Three babies have been born after receiving the worlds first spina bifida treatment combining surgery with stem cells. This was made possible by a landmark clinical trial at UC Davis Health.

The one-of-a-kind treatment, delivered while a fetus is still developing in the mothers womb, could improve outcomes for children with this birth defect.

Launched in the spring of 2021, the clinical trial is known formally as the CuRe Trial: Cellular Therapy for In Utero Repair of Myelomeningocele. Thirty-five patients will be treated in total.

The three babies from the trial that have been born so far will be monitored by the research team until 30 months of age to fully assess the procedures safety and effectiveness.

The first phase of the trial is funded by a $9 million state grant from the states stem cell agency, the California Institute for Regenerative Medicine (CIRM).

This clinical trial could enhance the quality of life for so many patients to come, said Emily, the first clinical trial participant who traveled from Austin, Tex. to participate. Her daughter Robbie was born last October. We didnt know about spina bifida until the diagnosis. We are so thankful that we got to be a part of this. We are giving our daughter the very best chance at a bright future.

Spina bifida, also known as myelomeningocele, occurs when spinal tissue fails to fuse properly during the early stages of pregnancy. The birth defect can lead to a range of lifelong cognitive, mobility, urinary and bowel disabilities. It affects 1,500 to 2,000 children in the U.S. every year. It is often diagnosed through ultrasound.

While surgery performed after birth can help reduce some of the effects, surgery before birth can prevent or lessen the severity of the fetuss spinal damage, which worsens over the course of pregnancy.

Ive been working toward this day for almost 25 years now, said Diana Farmer, the worlds first woman fetal surgeon, professor and chair of surgery at UC Davis Health and principal investigator on the study.

As a leader of the Management of Myelomeningocele Study (MOMS) clinical trial in the early 2000s, Farmer had previously helped to prove that fetal surgery reduced neurological deficits from spina bifida. Many children in that study showed improvement but still required wheelchairs or leg braces.

Farmer recruited bioengineer Aijun Wang specifically to help take that work to the next level. Together, they launched theUC Davis Health Surgical Bioengineering Laboratoryto find ways to use stem cells and bioengineering to advance surgical effectiveness and improve outcomes. Farmer also launched the UC Davis Fetal Care and Treatment Centerwith fetal surgeon Shinjiro Hirose and the UC DavisChildrens Surgery Center several years ago.

Farmer, Wang and their research team have been working on their novel approach using stem cells in fetal surgery for more than 10 years. Over that time, animal modeling has shown it is capable of preventing the paralysis associated with spina bifida.

Its believed that the stem cells work to repair and restore damaged spinal tissue, beyond what surgery can accomplish alone.

Preliminary work by Farmer and Wang proved that prenatal surgery combined with human placenta-derived mesenchymal stromal cells, held in place with a biomaterial scaffold to form a patch, helped lambs with spina bifida walk without noticeable disability.

When the baby sheep who received stem cells were born, they were able to stand at birth and they were able to run around almost normally. It was amazing, Wang said.

When the team refined their surgery and stem cells technique for canines, the treatment also improved the mobility of dogs with naturally occurring spina bifida.

A pair of English bulldogs named Darla and Spanky were the worlds first dogs to be successfully treated with surgery and stem cells. Spina bifida, a common birth defect in this breed, frequently leaves them with little function in their hindquarters.

By their post-surgery re-check at 4 months old, Darla and Spanky were able to walk, run and play.

When Emily and her husband Harry learned that they would be first-time parents, they never expected any pregnancy complications. But the day that Emily learned that her developing child had spina bifida was also the day she first heard about the CuRe trial.

For Emily, it was a lifeline that they couldnt refuse.

Participating in the trial would mean that she would need to temporarily move to Sacramento for the fetal surgery and then for weekly follow-up visits during her pregnancy.

After screenings, MRI scans and interviews, Emily received the life-changing news that she was accepted into the trial. Her fetal surgery was scheduled for July 12, 2021, at 25 weeks and five days gestation.

Farmer and Wangs team manufactures clinical grade stem cells mesenchymal stem cells from placental tissue in the UC Davis Healths CIRM-funded Institute for Regenerative Cures. The cells are known to be among the most promising type of cells in regenerative medicine.

The lab is aGood Manufacturing Practice(GMP) Laboratory for safe use in humans. It is here that they made the stem cell patch for Emilys fetal surgery.

Its a four-day process to make the stem cell patch, said Priya Kumar, the scientist at the Center for Surgical Bioengineering in the Department of Surgery, who leads the team that creates the stem cell patches and delivers them to the operating room. The time we pull out the cells, the time we seed on the scaffold, and the time we deliver, is all critical.

During Emilys historic procedure, a 40-person operating and cell preparation team did the careful dance that they had been long preparing for.

After Emily was placed under general anesthetic, a small opening was made in her uterus and they floated the fetus up to that incision point so they could expose its spine and the spina bifida defect. The surgeons used a microscope to carefully begin the repair.

Then the moment of truth: The stem cell patch was placed directly over the exposed spinal cord of the fetus. The fetal surgeons then closed the incision to allow the tissue to regenerate.

The placement of the stem cell patch went off without a hitch. Mother and fetus did great! Farmer said.

The team declared the first-of-its-kind surgery a success.

On Sept. 20, 2021, at 35 weeks and five days gestation, Robbie was born at 5 pounds, 10 ounces, 19 inches long via C-section.

One of my first fears was that I wouldnt be able to see her, but they brought her over to me. I got to see her toes wiggle for the first time. It was so reassuring and a little bit out of this world, Emily said.

For Farmer, this day is what she had long hoped for, and it came with surprises. If Robbie had remained untreated, she was expected to be born with leg paralysis.

It was very clear the minute she was born that she was kicking her legs and I remember very clearly saying, Oh my God, I think shes wiggling her toes! said Farmer, who noted that the observation was not an official confirmation, but it was promising. It was amazing. We kept saying, Am I seeing that? Is that real?

Both mom and baby are at home and in good health. Robbie just celebrated her first birthday.

The CuRe team is cautious about drawing conclusions and says a lot is still to be learned during this safety phase of the trial. The team will continue to monitor Robbie and the other babies in the trial until they are 6 years old, with a key checkup happening at 30 months to see if they are walking and potty training.

This experience has been larger than life and has exceeded every expectation. I hope this trial will enhance the quality of life for so many patients to come, Emily said. We are honored to be part of history in the making.

Related links

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World's first stem cell treatment for spina bifida delivered during fetal surgery - UC Davis Health

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When I was young,,,

36 reasons to VOTE YES! For Your Scientist Friends

By Don C. Reed

Author, STEM CELL BATTLES, other books

http://www.stemcellbattles.com

Dear Friend of Regenerative Medicine:

For the next month, I will make available a daily summary of one aspect of stem cell researchmy laymans understanding of itdone by scientists connected to the California Institute for Regenerative Medicine (CIRM). Todays is spina bifida, tomorrow is stroke.

Mistakes are mine.

In most cases I have left out the scientists names. A few I have written about in my books, and those I felt free to credit.

All I ask is that when you step into the voting booth, please consider which political party is likely to fund such research, and vote accordingly.

Spina Bifida: total awards (3) Award value: $16,798,263

The condition is devastating, and lasts a lifetime. The baby has a part of its spine bulging out of its lower back. Accompanying symptoms are many, including: headaches, vomiting, weakness in the legs, bladder and bowel problems.

Current standard of care (in utero surgery) leaves 58% of patients unable to walk independently.

39% of affected population are Hispanic or Latino descent.

The condition may cost several million dollars per patient, over his or her lifetime.

Spina Bifida (SB) appears to be caused by a combination of genetic and environmental conditions, but no one is sure. How will CIRM fight such a thing?

One way is Placenta-derived mesenchymal stem cells, seeded on a Cook Biodesign extracellular Matrix. Think of a mesh screen, over the wound.

THERAPEUTIC MECHANISM: Mesenchymal stem cellssecrete growth factors (and) cytokinesprotecting motor neurons from cell deathtreatment increases the density of motor neurons in the spinal cord, leading to improved motor functionultimately reducing lower limb paralysis. (1)

Grant recipient Diana Farmer began science as a marine biologist, who doing research at the famous Woods Hole Institute. On the way to receive an award, she suffered a car accident, and changed her mind, working on human biology. She was the first woman to perform surgery on a baby in its mothers womb. (1)

She and Aijun Wang received a CIRM grant to co-launch the worlds first human clinical trial using stem cells to treat spina bifida.. (2)

1. https://en.wikipedia.org/wiki/Diana_L._Farmer

2. https://health.ucdavis.edu/health-news/newsroom/state-stem-cell-agency-funds-clinical-trial-for-spina-bifida-treatment/2020/11

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Fighting One Disease or Condition per Day - Daily Kos

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Both companies will collaborate to improve NurExone's drug development stages, from R&D to Quality Assurance

Company to host an investor webinar on Thursday, October 20th, 2022 at 11:00 AM EST

Calgary, Alberta and Oxford, United Kingdom--(Newsfile Corp. - October 12, 2022) - NurExone Biologic Inc. (TSXV: NRX) (FSE: J90) (the "Company" or "NurExone"), a biopharmaceutical company developing biologically-guided exosome therapy for patients with traumatic spinal cord injuries, is pleased to announce that the Company's wholly-owned subsidiary, NurExone Biologic Ltd., signed a non-binding Letter of Intent for a collaboration (the "Collaboration") with Nanometrix Ltd. ("Nanometrix"), a U.K.-based nanoparticle analysis company providing services to profile molecules of exosomes and their cargo.

Under the Collaboration, NurExone's exosomes and cargo samples will be processed and analyzed by Nanometrix, which will use its proprietary Artificial Intelligence (AI) software to extract and analyze morphological and population data to achieve detailed molecular profiling of the exosomes and quantify the siRNA cargo copy number per extracellular vesicle (EV), information which was far out of reach.

"Detailed molecular profiling of our exosomes and their siRNA cargo will facilitate a quality assurance program for repeatable, mass-production of ExoTherapies towards commercialization," said Dr. Lior Shaltiel, CEO of NurExone. "Nanometrix has the expertise and resources to perform this analysis in a highly professional manner and we look forward to working with them."

"The signing of this letter of intent is a first step towards a great milestone for Nanometrix," said Alexandre Kitching, CEO and Cofounder of Nanometrix. "We are thrilled to start this collaboration with NurExone as we believe in the future of exosomes as an advanced platform for drug delivery. We look forward to deploying our technology and assisting NurExone in gaining in-depth information about their siRNA-loaded exosomes and subsequently, improving the different stages of their drug development process."

Story continues

Exosomes are best defined as EVs that have emerged as promising guided nanocarriers for drug delivery and targeted therapy, and as alternatives to stem cell therapy. EVs are endosome-derived small membrane vesicles, approximately 30 to 150 nanometres in diameter, and are released into extracellular fluids by cells in all living systems. They are well-suited for small functional molecule delivery, and increasing evidence indicates that they have a pivotal role in cell-to-cell communication.

NurExone's ExoTherapy uses proprietary exosomes as biologically-guided nanocarriers to deliver specialized therapeutic compounds to targeted areas. The delivered molecules promote an environment that induces a healing process at the target location. For its first clinical indication of providing recovery of function to traumatic spinal cord injury (SCI) patients, NurExone used modified siRNA sequences as the delivered therapeutic molecules.

ExoTherapy is being developed as a revolutionary "off-the-shelf" intranasal product to treat traumatic spinal cord and brain injuries as well as other Central Nervous System indications. In preclinical studies of rats with a fully transected spinal cords, intranasal administration of ExoPTEN led to significant motor improvement, sensory recovery, and faster urinary reflex restoration.

Investor Webinar

The Company will be hosting a webinar to discuss its recent business highlights and growth outlook on Thursday, October 20th, 2022 at 11:00 AM EST.

Please click the link below to register for the webinar.https://us02web.zoom.us/webinar/register/WN_hqlWt1EUTrCy_ol_iJ2DmA

About Nanometrix

Nanometrix is a nanoparticle analysis start-up based in Oxford, UK that has developed unique end-to-end services to routinely create molecular profiles of nanoparticles from samples. Each profile delivers information currently out of reach such as the morphology, population dynamics and cargo copy number per nanoparticle. Nanometrix's software and services are currently deployed across labs and teams globally working on the development of novel therapeutics and diagnostics.

For additional information, please visit http://www.nanometrix.bio or contact us at info@nanometrix.bio

About NurExone Biologic Inc.

NurExone Biologic Inc. is a TSXV listed pharmaceutical company that is developing a platform for biologically-guided ExoTherapy to be delivered, non-invasively, to patients who suffered traumatic spinal cord injuries. ExoTherapy was conceptually demonstrated in animal studies at the Technion, Israel Institute of Technology. NurExone is translating the treatment to humans, and the company holds an exclusive worldwide license from the Technion for the development and commercialization of the technology.

For additional information, please visit http://www.nurexone.com or follow NurExone on LinkedIn, Twitter, Facebook, or YouTube.

For more information, please contact:

Inbar Paz-BenayounHead of CommunicationsPhone: +972-52-3966695Email: info@nurexone.com

For investors:Investor RelationsIR@nurexone.com+1 905-347-5569

FORWARD-LOOKING STATEMENTS

This press release contains certain forward-looking statements, including statements about the Company's future plans, the Letter of Intent, the development activities to be carried out pursuant to the Collaboration, the potential entering into of a commercial agreement between the parties and future potential manufacturing and marketing activities. Wherever possible, words such as "may", "will", "should", "could", "expect", "plan", "intend", "anticipate", "believe", "estimate", "predict" or "potential" or the negative or other variations of these words, or similar words or phrases, have been used to identify these forward-looking statements. These statements reflect management's current beliefs and are based on information currently available to management as at the date hereof. Forward-looking statements involve significant risk, uncertainties and assumptions. Many factors could cause actual results, performance or achievements to differ materially from the results discussed or implied in the forward-looking statements. These risks and uncertainties include, but are not limited to, risks related to the Company's early stage of development, lack of revenues to date, government regulation, market acceptance for its products, rapid technological change, dependence on key personnel, protection of the Company's intellectual property and dependence on the Company's strategic partners. These factors should be considered carefully and readers should not place undue reliance on the forward-looking statements. Although the forward-looking statements contained in this press release are based upon what management believes to be reasonable assumptions, the Company cannot assure readers that actual results will be consistent with these forward-looking statements. These forward-looking statements are made as of the date of this press release, and the Company assumes no obligation to update or revise them to reflect new events or circumstances, except as required by law.

Neither TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release.

NurExone is providing an updated release to the previously disseminated release from earlier today to remove a paragraph that was included in error.

To view the source version of this press release, please visit https://www.newsfilecorp.com/release/140289

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UPDATE: NurExone Signs Letter of Intent with Nanometrix for Its Exosome and Cargo Molecular Profiling AI-Driven Technology - Yahoo Finance

Spinal Cord Stem Cells Comments Off on UPDATE: NurExone Signs Letter of Intent with Nanometrix for Its Exosome and Cargo Molecular Profiling AI-Driven Technology – Yahoo Finance | October 13th, 2022

DUBLIN--(BUSINESS WIRE)--The "Global Cell Therapy Market, By Use Type, By Therapy Type, By Product, By Technology & By Region- Forecast and Analysis 2022-2028" report has been added to ResearchAndMarkets.com's offering.

The Global Cell Therapy Market was valued at USD 14.86 Billion in 2021, and it is expected to reach a value of USD 35.95 Billion by 2028, at a CAGR of 13.45% over the forecast period (2022 - 2028).

Companies Mentioned

The cell therapy industry is being propelled forward by an increase in the number of clinical trials for cell-based treatments. As a result, global investment in research and clinical translation has increased significantly. The increasing number of ongoing clinical studies can be attributed to the presence of government and commercial funding bodies that are constantly providing funds to assist projects at various stages of clinical trials.

Top-down and bottom-up approaches were used to estimate and validate the size of the Global Cell Therapy Market and to estimate the size of various other dependent submarkets. The research methodology used to estimate the market size includes the following details: The key players in the market were identified through secondary research and their market shares in the respective regions were determined through primary and secondary research.

This entire procedure includes the study of the annual and financial reports of the top market players and extensive interviews for key insights from industry leaders such as CEOs, VPs, directors, and marketing executives.

All percentage shares split, and breakdowns were determined by using secondary sources and verified through Primary sources. All possible parameters that affect the markets covered in this research study have been accounted for, viewed in extensive detail, verified through primary research, and analyzed to get the final quantitative and qualitative data.

Segments covered in this report

The global cell therapy market is segmented based on Use-type, Therapy Type, Product, Technology, Application, and Region. Based on Use-type it is categorized into Clinical-use, and Research-use. Based on Therapy Type it is categorized into Allogenic Therapies, Autologous Therapies.

Based on Product it is categorized into Consumables, Equipment, Systems, and Software. Based on Technology it is categorized into Viral Vector Technology, Genome Editing Technology, Somatic Cell Technology, Cell Immortalization Technology, Cell Plasticity Technology, and Three-Dimensional Technology. Based on the region it is categorized into North America, Europe, Asia-Pacific, South America, and MEA.

Drivers

The increased demand for novel, better medicines for diseases such as cancer and CVD has resulted in an increase in general research efforts as well as funding for cell-based research. In November 2019, the Australian government released The Stem Cell Therapies Mission, a 10-year strategy for stem cell research in Australia.

The project would receive a USD 102 million (AU$150 million) grant from the Medical Research Future Fund (MRFF) to encourage stem cell research in order to develop novel medicines. Similarly, the UK's innovation agency, Innovate the UK, awarded USD 269,670 (GBP 267,000) in funding in September 2019 to Atelerix's gel stabilization technologies, with the first goal of extending the shelf-life of Rexgenero's cell-based therapies for storage and transport at room temperature.

Restraints

Despite technological advancements and product development over the last decade, the industry has been hampered by a lack of skilled personnel to operate complex devices like flow cytometers and multi-mode readers. Flow cytometers and spectrophotometers, which are both technologically advanced and extremely complex, generate a wide range of data outputs that require skill to analyze and review.

There is a global demand-supply mismatch for competent individuals, according to the National Accrediting Agency for Clinical Laboratory Sciences (NAACLS). Over the next decade, the UK and Europe are expected to face a severe shortage of lab capabilities, with medical laboratories being particularly hard hit.

Market Trends

The expansion of the cell therapy market was aided by the growing frequency of chronic illnesses. Chronic illness is defined as a condition that lasts one year or more and requires medical treatment, affects everyday activities, or both, according to the US Centers for Disease Control and Prevention (CDC).

It includes heart disease, cancer, diabetes, and Parkinson's disease. Patients with spinal cord injuries, type 1 diabetes, Parkinson's disease (PD), heart disease, cancer, and osteoarthritis may benefit from stem cells.

For more information about this report visit https://www.researchandmarkets.com/r/aqmxta

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Global Cell Therapy Market Report (2022 to 2028) - Featuring Thermo Fisher Scientific, MaxCyte, Danaher and Avantor Among Others -...

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DUBLIN--(BUSINESS WIRE)--Horizon Therapeutics plc (Nasdaq: HZNP) today announced that new UPLIZNA analyses will be presented at the 38th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2022, Oct. 26-28. UPLIZNA is the first and only anti-CD19 B-cell-depleting humanized monoclonal antibody approved by the U.S. Food and Drug Administration (FDA) and European Commission (EC) for the treatment of adult patients with anti-aquaporin-4 (AQP4) antibody positive NMOSD.

Presentation Details:

In addition, Horizon will host a symposium Thursday, Oct. 27 from 8:45-9:45 a.m. CEST called Step into the new era of NMOSD, chaired by Hans-Peter Hartung, M.D., Ph.D. and featuring presentations from Jrme de Sze Ph.D., Brian Weinshenker, M.D., and Orhan Aktas, M.D. Topics will include NMOSD diagnosis and care, advantages of CD19 treatments and the clinical relevance of UPLIZNA in NMOSD.

About Neuromyelitis Optica Spectrum Disorder (NMOSD)

NMOSD is a unifying term for neuromyelitis optica (NMO) and related syndromes. NMOSD is a rare, severe, relapsing, neuroinflammatory autoimmune disease that attacks the optic nerve, spinal cord, brain and brain stem.1,2 Approximately 80% of all patients with NMOSD test positive for anti-AQP4 antibodies.3 AQP4-IgG binds primarily to astrocytes in the central nervous system and triggers an escalating immune response that results in lesion formation and astrocyte death.4

Anti-AQP4 autoantibodies are produced by plasmablasts and some plasma cells. These B-cell populations are central to NMOSD disease pathogenesis, and a large proportion of these cells express CD19.5 Depletion of these CD19+ B-cells is thought to remove an important contributor to inflammation, lesion formation and astrocyte damage. Clinically, this damage presents as an NMOSD attack, which can involve the optic nerve, spinal cord and brain.4,6 Loss of vision, paralysis, loss of sensation, bladder and bowel dysfunction, nerve pain and respiratory failure can all be manifestations of the disease.7 Each NMOSD attack can lead to further cumulative damage and disability.8,9 NMOSD occurs more commonly in women and may be more common in individuals of African and Asian descent.10,11

About UPLIZNA

INDICATION

UPLIZNA is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.

IMPORTANT SAFETY INFORMATION

UPLIZNA is contraindicated in patients with:

WARNINGS AND PRECAUTIONS

Infusion Reactions: UPLIZNA can cause infusion reactions, which can include headache, nausea, somnolence, dyspnea, fever, myalgia, rash or other symptoms. Infusion reactions were most common with the first infusion but were also observed during subsequent infusions. Administer pre-medication with a corticosteroid, an antihistamine and an anti-pyretic.

Infections: The most common infections reported by UPLIZNA-treated patients in the randomized and open-label periods included urinary tract infection (20%), nasopharyngitis (13%), upper respiratory tract infection (8%) and influenza (7%). Delay UPLIZNA administration in patients with an active infection until the infection is resolved.

Increased immunosuppressive effects are possible if combining UPLIZNA with another immunosuppressive therapy.

The risk of Hepatitis B Virus (HBV) reactivation has been observed with other B-cell-depleting antibodies. Perform HBV screening in all patients before initiation of treatment with UPLIZNA. Do not administer to patients with active hepatitis.

Although no confirmed cases of Progressive Multifocal Leukoencephalopathy (PML) were identified in UPLIZNA clinical trials, JC virus infection resulting in PML has been observed in patients treated with other B-cell-depleting antibodies and other therapies that affect immune competence. At the first sign or symptom suggestive of PML, withhold UPLIZNA and perform an appropriate diagnostic evaluation.

Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating UPLIZNA.

Vaccination with live-attenuated or live vaccines is not recommended during treatment and after discontinuation, until B-cell repletion.

Reduction in Immunoglobulins: There may be a progressive and prolonged hypogammaglobulinemia or decline in the levels of total and individual immunoglobulins such as immunoglobulins G and M (IgG and IgM) with continued UPLIZNA treatment. Monitor the level of immunoglobulins at the beginning, during, and after discontinuation of treatment with UPLIZNA until B-cell repletion especially in patients with opportunistic or recurrent infections.

Fetal Risk: May cause fetal harm based on animal data. Advise females of reproductive potential of the potential risk to a fetus and to use an effective method of contraception during treatment and for 6 months after stopping UPLIZNA.

Adverse Reactions: The most common adverse reactions (at least 10% of patients treated with UPLIZNA and greater than placebo) were urinary tract infection and arthralgia.

For additional information on UPLIZNA, please see the Full Prescribing Information at http://www.UPLIZNA.com.

About Horizon

Horizon is a global biotechnology company focused on the discovery, development and commercialization of medicines that address critical needs for people impacted by rare, autoimmune and severe inflammatory diseases. Our pipeline is purposeful: We apply scientific expertise and courage to bring clinically meaningful therapies to patients. We believe science and compassion must work together to transform lives. For more information on how we go to incredible lengths to impact lives, visit http://www.horizontherapeutics.com and follow us on Twitter, LinkedIn, Instagram and Facebook.

References

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Introduction

Within the spinal column lies the spinal cord, a vital aspect of the central nervous system (CNS). The three primary roles of the spinal cord are to send motor commands from the brain to the body, send sensory information from the body to the brain, and coordinate reflexes. The spinal cordis organized segmentally, with thirty-one pairs of spinal nerves emanating from it. A spinal cord injury disrupts this conduit between the body and brain and canlead to deficits in sensation, movement, and autonomic regulation, as well as death.

The spinal cord is composed of gray and white matter, appearing in a cross-section as H-shaped gray matter surrounded by white matter. The gray matter consists of the cell bodies of motor and sensory neurons, interneurons,and neuropils (neuroglia cells and mostly unmyelinated axons). In contrast, the white matter is composed of interconnecting fiber tracts, which are primarily myelinated sensory and motor axons. The supports of the gray matters H make up the right dorsal, right ventral, left dorsal, and left ventral horns. Running longitudinally through the center of the spinal cord is the central canal, which is continuous with the brains ventricles and filled with cerebrospinal fluid (CSF).

The white matteris organized into tracts. Ascending tracts carry information from the sensory receptors to higher levels of the CNS, while descending tracts carry information from theCNS to the periphery. The major tracts and their most defining features are as follows:[1]

Ascending Tracts

Dorsal column: contains the gracile fasciculus and cuneate fasciculus, which togetherform the dorsal funiculus. The dorsal column is responsible for pressure and vibration sensation, two-point discrimination, movement sense, and conscious proprioception. The dorsal column decussates at the superior portion of the medulla oblongata and forms the medial lemniscus.

Lateral spinothalamic: carries pain and temperature information. The lateral spinothalamic tract decussates at the anterior commissure, two segments above the entry to the spinal cord.

Descending Tracts

Lateral and anterior corticospinal: involved in conscious control of the skeletal muscle. The majority of lateral corticospinal tract fibers decussate at the inferior portion of the medulla oblongata, while anterior corticospinal descends ipsilaterally in the spinal cord and decussates at the segmental level. The lateral corticospinal tract, also called the pyramidal tract, innervates primarily contralateralmuscles of the limbs, while the anterior corticospinal tract innervates proximal muscles of the trunk.

Vestibulospinal: carries information from the inner ear to control head positioning and is involved in modifying muscle tone to maintain posture and balance. The vestibulospinal tract does not decussate.

Rubrospinal: involved in the movement of the flexor and extensor muscles.The rubrospinal tract originates from the red nuclei in the midbrain and decussates at the start of its pathway.

There is a laminar distribution of neurons in the gray matter, characterized by density and topography:

Lamina II is composed mainly of islet cells with rostrocaudal axes, which contain GABA and are thought to be inhibitory, and stalked cells with dorsoventral dendritic trees.

Lamina V and VI are composed of medium-sized multipolar neurons that can be fusiform or triangular. These neurons communicate with the reticular formation of the brainstem.

Lamina VII is composed of homogenous medium-sized multipolar neurons and contains, in individual segments, well-defined nuclei, including the intermediolateral nucleus (T1-L1), which has autonomic functions, and the dorsal nucleus of Clarke (T1-L2), which make up the dorsal spinocerebellar tract.

Lamina VIII consists of neurons with dorsoventrally polarized dendritic trees.

Lamina IX has the cell bodies of motor neurons, with dendrites extending dorsally into laminas as far as VI. Lamina IX also has Renshaw cells, inhibitory interneurons, placed at the medial border of motor nuclei.

Neurulation begins in the trilaminar embryo when part of the mesoderm differentiates into the notochord. The formation of the notochord signals the overlying ectoderm to form the neural plate, the first structure that will become the nervous system. The neural plate folds in on itself, creating the neural tube, initially open at both ends and ultimately closed. From the neural tube comes the primitive brain and spinal cord.[9]The development of the nervous system begins seventeen days after gestation, and in the fifth week, myotomes start to form, allowing the development of rudimentary reflex circuitries. Myelination of the motor tracts begins in the first few months of life and continues into adolescence.

An interesting note is that reciprocal excitation changes to inhibition between nine and twelve months of age. Before that age, supraspinal descending fibers activate interneurons, resulting in extension or flexion. During this period of development, glycine and GABA are excitatory.[10]

The spinal cord is the conduit between the brain and the rest of the body. It sends motor commands from the motor cortex to the muscles of the body and sensory information from the afferent fibers to the sensory cortex. Additionally, the spinal cord can act without signals from the brain in certain instances. The spinal cord independently coordinates reflexes using reflex arcs.Reflex arcs allow the body to respond to sensory information without waiting for input from the brain. The reflex arc starts with a signal from a sensory receptor, which is carried to the spinal cord via a sensory nerve fiber, synapsed on an interneuron, carried over to the motor neuron, which stimulates an effector muscle or organ.[11]The spinal cord also has central pattern generators, which are interneurons that form the neural circuits, which control rhythmic movements. Although the existence of central pattern generators in humans is controversial, the lumbar spinal cord produces rhythmic muscle activation without volitional motor control or step-specific sensory feedback, suggesting their role in human movement.[12]

Three connective tissue layers,termed meninges, conceal the spinal cord. Directly lining the spinal cord is the pia mater, which also thickens to form the denticulate ligament, anchoring the spinal cord in the middle of the vertebral canal. The next layer of meninges is the arachnoid mater.Between the pia mater and arachnoid mater is the subarachnoid space, which contains CSF. On top of the arachnoid mater is the last layer of meninges, the dura mater, then the epidural space separating the meninges from the vertebral column.[13]

The spinal cord extends from the medulla oblongata of the brain stem at the level of the foramen magnum. In an adult human, the spinal cord gives rise to thirty-one pairs of spinal nerves, each of which originates from the adjacent spinal cord segment:

Spinal nerves emerge from the spinal cord as rootlets, whichjoin together to form two nerve roots.The anterior nerve roots contain motor fibers extending from the anterior horn to peripheral target organs. The motor neurons are multipolar, with at least two dendrites, a single axon, and one or more collateral branches. They control skeletal muscles and the autonomic nervous system. The posterior nerve roots contain sensory fibers and dorsal root ganglia. They contain sensory fibers transmitting sensory information from the periphery towards the CNS. The sensory neurons located at the dorsal root ganglia are pseudounipolar. The anterior and posterior nerve roots converge into spinal nerves, which split into dorsal and ventral rami.A dermatome is a skin area innervated by a single spinal nerve root (or spinal cord segment).

There are five spinal plexuses, which include sensory and motor nerves from the anterior rami:

Cervical plexus (C1-C5): the deep branches innervate neck muscles, and the superficial branches innervate the skin on the neck, head, and chest. The cranial plexus also has an autonomic function, including controlling the diaphragm and interactions with the vagus nerve.

Brachial (C5-T1): controls movement and sensation of the upper extremity.

Lumbar (L1-L4): controls movement and sensation of the abdominal wall, thigh, and external genitals.

Sacral (L4, L5, S1-S4): controls movement and sensation of the foot, leg, and thigh.

Coccygeal (S4, S5, Co): innervates the skin around the tailbone.

In adults, the spinal cord tapers to an end, termed the conus medullaris, at the second lumbar vertebra level. Past the conus medullaris, a bundle of spinal roots extends termed the cauda equina. The cauda equina and the subarachnoid space continue until S2 and is the target location for a lumbar puncture (spinal tap).

Electrophysiological Testing

Evoked potentials (EPs) measure electrical signals going to the brain and can determine whether there is motor or somatosensory impairment. The signal is detected by electroencephalography (EEG) or electromyography (EMG). Evoked potentialsmay be used to assess spinal cord damage in the setting of spinal cord injury and tumors, and measure functional impairment and predict disease progression in multiple sclerosis.[15]Somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs)are frequentlyused intra-operatively for monitoring and can be used post-operatively as surrogate endpoints to check muscle strength and sensory status.[16]

Nerve conduction studies determine whether there has been an injury to a spinal nerve root, peripheral nerve, neuromuscular junction, muscle, cranial nerve, or spinal nerve. They can also be used to pinpoint spinal cord lesions.Nerve conduction studies work by stimulating nerves close to the skin or using a needle placed near a nerve or nerve root. Neurologists often use them with needle electromyograms.[17]

Lumbar Puncture

A lumbar puncture, or spinal tap, samples the CSF from the subarachnoid space. The needle to obtain the sample should be inserted between lumbar spinal canal levels L3 and L4 to avoid contact with the spinal cord.[18]TheCSF is then sent to a laboratory to establish whether any insult can be determined.For instance, a lumbar puncture can confirm or exclude bacterial meningitis, which will produce a cloudy fluid suggestive of a high leukocyte count. It is also important to know when not to use a lumbar puncture. Contraindications to lumbar puncture include signs of cerebral herniation, focal neurological signs, uncorrected coagulopathies, or cardiorespiratory compromise.[19]

Deep Tendon Testing

One aspect of theneurological exam is a test of the deep tendon reflexes, which are involuntary motor responses to various stimuli that function via reflex arcs within the spinal cord. They can be used to test the function of the motor and sensory nerves at specific spinal cord levels.Reflex grading is on a scale of 0 (absent reflex) to 5+ (sustained clonus).[20]Some commonly tested reflexes are as follows:

Additionally, the Babinski reflex, or the extensor plantar reflex, can be seen in newborns but is an abnormal response aftersix to twelve months of age. If the Babinski reflex is seen after 12 months of age, it may indicate an abnormality in the corticospinal system.[21]

Spinal Cord Injury

Primary spinal cord injury occurs due to local deformation of the spine, such as direct compression. Secondary spinal cord injury occurs following primary damage and involves cascades of biochemical and cellular processes, including electrolyte disturbances, free radical damage, edema, ischemia, and inflammation.[22]Secondary spinal cord injury has several phases: acute, subacute, and chronic. During the acute phase (up to 48 hours after the primary injury), hemorrhage and ischemia lead to ion balance disruption, excitotoxicity, and inflammation. During the subacute phase (up to two weeks following primary injury), there is a phagocytic response and a reactive proliferation of astrocytes, which leads to a glial scar in the chronic phase. The thinking is that scarification is the critical component to permanent disability because it prevents axonal regeneration; axons otherwise could regenerate, but their growth is blocked. However, that notion has been subject to challenge, and there are suggestions that astrocyte scar formation could aid in regeneration.[23]In the chronic phase (over six months after the primary injury), the scarification process is complete.[24]

Developmental

Open neural tube defects occur when there is a failure of the neural tube to close. If it fails to close at the cranial end, the fetusmay develop anencephaly. If the failure is at the caudal end, the fetusmay have myelomeningocele or open spina bifida. Craniorachischisis can also occur if the entire neural tube remains open. Closed neural tube defects are spinal cord development problems that are skin-covered, such as occult spina bifida.Folic acid supplements lower the risk of neural tube defects, although severe folate deficiency in mouse models does not lead to neural tube defects unless there is already a genetic predisposition. Suggestions are that folate can overcome a genetic predispositionfor adverse effects, potentially leading to neural tube defects.[25]

A spinal cord injury can be classified as complete or incomplete. A complete injury, based on the International Standard Neurological Classification of Spinal Cord Injury (ISNCSCI) examination, developed by the American Spinal Cord Injury Association (ASIA), implies that there is no sensation at the inferior segments of the spinal cord (S4-S5); no deep anal pressure (DAP) or voluntary anal contraction (VAC) is present. If no perianal sensation is present and DAP and VAC are absent, the present function below the level of injury is a zone of partial preservation.[26]

An injury in the cervical region often results in quadriplegia if both sides of the spinal cord are affected and hemiplegia if only one side is affected. Nerves from C3, C4, and C5 stimulate the phrenic nerve, which controls the diaphragm, so injury to C4 and above may result in a permanent need for a ventilator. An injury to the thoracic region often limits the function of nerves related to the lower torso and lower extremities. Usually, it does not affect the upper torso and upper extremities, except in rare cases such as subacute posttraumatic ascending myelopathy (SPAM).[27]Injury to thespinal cord often causes loss of bowel and bladder control, loss of sexual function, and blood pressure dysregulation, as the spinal cordrelays autonomic and somatic information.

Syndromes

Several syndromes correlate with spinal cord injury. Central cord syndrome usually occurs in individuals who suffer a hyperextension injury, and it often leads to incomplete injury with weakness predominantly affecting the upper limbs. The reason for this phenomenon is the organization of the fibers in the spinal cord: the fibers running to the lower extremities are longer than those running to the upper extremities; the longer fibers are located more laterally in the spinal cord (L-L rule). As the central portion of the spinal cord is injured, there is a sparing of the fibers running to the lower extremities. Brown-Sequard syndrome is due to a spinal cord hemisection,leading to a complete loss of sensation at the level of the lesion, as well as deficits below the lesion loss of proprioception, vibration, and motor control, ipsilaterally, and a loss of pain and temperature sensation, contralaterally. Anterior cord syndrome is due to a compromised blood supply to the anterior two-thirds of the spinal cord, damaging the corticospinal and spinothalamic tracts.This syndrome is associated with several deficits at and below the lesion, including motor loss and a loss of pain and temperature sensation. However, light touch and joint position sense from the dorsal columns are left intact.[26]Injury to T12-L2 segmentsmay result in conus medullaris syndrome, while injury to L3-L5 segmentscan lead to cauda equina syndrome. Usually, these syndromes present as incomplete injuries and result in neurogenic bladder and/or bowel, loss of sexual function, and perianal loss of sensation.[28]

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BRENTWOOD, Tenn., Sept. 09, 2022 (GLOBE NEWSWIRE) -- IMAC Holdings, Inc. (Nasdaq: BACK) (IMAC or the Company), today announces it has completed the third cohort of its Phase 1 clinical trial for its investigational compound utilizing umbilical cord-derived allogenic mesenchymal stem cells for the treatment of bradykinesia due to Parkinsons disease.

The third cohort consists of five patients with bradykinesia due to Parkinsons disease receiving an intravenous infusion of a high concentration stem cell treatment. The third and final cohort of the Phase 1 clinical trial was completed on Tuesday, September 6, 2022.

About IMACs Phase 1 Clinical Trial

The Phase 1 clinical trial, consisting of a 15-patient dose escalation safety and tolerability study, is being conducted at three of IMACs clinical centers in Chesterfield, Missouri, Paducah, Kentucky, and Brentwood, Tennessee. The trial is divided into three groups: 1) five patients with bradykinesia due to Parkinsons disease received a low concentration dose, intravenous infusion of stem cells, 2) five received a medium concentration intravenous dose, 3) and five received a high concentration intravenous dose. All groups will be subsequently tracked for 12 months. IMACs medical doctors and physical therapists at the clinical sites have been trained to administer the treatment and manage the therapy. Ricardo Knight, M.D., M.B.A., who is medical director of the IMAC Regeneration Center of Chicago, is the trials principal investigator.

The Institute of Regenerative and Cellular Medicine serves as the trials independent investigational review board, while Regenerative Outcomes provides management of the study. Further details of the trial can be found at clinicaltrials.gov.

About Bradykinesia Due to Parkinsons Disease

In addition to unusually slow movements and reflexes, bradykinesia may lead to limited ability to lift arms and legs, reduced facial expressions, rigid muscle tone, a shuffling walk, and difficulty with repetitive motion tasks, self-care, and daily activities. Parkinsons disease is the typical culprit of bradykinesia, and as it progresses through its stages, a persons ability to move and respond declines.

According to Zion Market Research, the global Parkinsons disease therapeutics market was $2.61 billion in 2018 and is expected to grow to $5.28 billion by 2025. The Parkinsons Disease Foundation estimates that nearly 10 million people are suffering from Parkinsons disease, and almost 60,000 new cases are reported annually in the U.S.

About IMAC Holdings, Inc.

IMAC Holdingsowns and manages health and wellness centers that deliver sports medicine, orthopedic care, and restorative joint and tissue therapies for movement restricting pain and neurodegenerative diseases.IMACis comprised of three business segments: outpatient medical centers, The Back Space, and a clinical research division. With treatments to address both young and aging populations,IMAC Holdingsowns or manages outpatient medical clinics that deliver regenerative rehabilitation services as a minimally invasive approach to acute and chronic musculoskeletal and neurological health problems. IMACs The Back Company retail spinal health and wellness treatment centers deliver chiropractic care within Walmart locations. IMACs research division is currently conducting a Phase I clinical trial evaluating a mesenchymal stem cell therapy candidate for bradykinesia due to Parkinsons disease. For more information visitwww.imacholdings.com.

# # #

Safe Harbor Statement

This press release contains forward-looking statements. These forward-looking statements, and terms such as anticipate, expect, believe, may, will, should or other comparable terms, are based largely on IMAC's expectations and are subject to a number of risks and uncertainties, certain of which are beyond IMAC's control. Actual results could differ materially from these forward-looking statements as a result of, among other factors, risks and uncertainties associated with its ability to raise additional funding, its ability to maintain and grow its business, variability of operating results, its ability to maintain and enhance its brand, its development and introduction of new products and services, the successful integration of acquired companies, technologies and assets, marketing and other business development initiatives, competition in the industry, general government regulation, economic conditions, dependence on key personnel, the ability to attract, hire and retain personnel who possess the skills and experience necessary to meet customers requirements, and its ability to protect its intellectual property. IMAC encourages you to review other factors that may affect its future results in its registration statement and in its other filings with the Securities and Exchange Commission. In light of these risks and uncertainties, there can be no assurance that the forward-looking information contained in this press release will in fact occur.

IMAC Press Contact:

Laura Fristoe

lfristoe@imacrc.com

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The green colors are increased synapses resulting from a regeneration in nerve axons SWNS

A revolutionary treatment that could repair spinal cord injuries has been developed by scientists which regrew nerves in paralyzed mice within three months.

The medication triggers cells of long spindly parts of the severed nerves called axons to regenerative themselves.

Currently, spinal cord injury does not have any effective treatments that involves a repairing of what was damaged. Physical rehabilitation can help patients regain some mobility, and a number of electrical stimulation technologies can stimulate nerves and muscles to act as before, but never with the precision of the real thing.

This work shows a drug called TTK21 that is administered systemically once a week after a chronic spinal cord injury in animals can promote neuronal regrowth and an increase in synapses that are needed for neuronal transmission, said lead author Dr. Simone Di Giovanni, of Imperial College London.

This is important because chronic spinal cord injury is a condition without a cure where neuronal regrowth and repair fail.

Damage to the spinal cord interrupts the constant stream of electrical signals from the brain to the body. It can lead to paralysis below an injury.

The study published in the journal PLOS Biology showed TTK21 aided the regrowth of sensory and motor neurons when given to mice 12 weeks after severe injury.

It belongs to a group of therapies known as epigenetic activators which target damaged DNA.

In experiments, lab rodents with severe spinal cord injury lived in an enriched environment with opportunities to be physically activeas is encouraged in human patients.

Treatment lasted for 10 weeks. Several improvements were identified, the most noticeable being the sprouting of more axons in the spinal cord. Retraction of motor axons above the point of injury was also halted, and sensory axon growth increased.

SIMILAR: Movement in Paralyzed Arms is Restored by Zapping Spinal Cords With Electrical Stimulation

The next step will be to boost the effects even more and get regenerating axons to reconnect to the rest of the nervous system so animals can regain their ability to move with ease.

We are now exploring the combination of this drug with strategies that bridge the spinal cord gap such as biomaterials as possible avenues to improve disability in SCI patients, said Di Giovanni.

For decades, this has remained a major challenge. Our bodys central nervous system, which includes the brain and spinal cord, does not have any significant capacity to repair itself.

RELATED: First Time Someone With Cut Spinal Cord is Able to Walk Freely, Thanks to New Swiss Technology

In the U.S., an estimated 300,000 people and another 50,000 in the UK are living with a spinal cord injury.

Last year GNN reported that Yale had used stem cells to repair patients injured spinal cords, which could be another future avenue to repairing nerves and axons.

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Oxytocin is a neurohormone called the love hormone because it promotes social bonds and generates pleasurable feelings.

It also regulates lactation, uterine contractions, the movement of sperm, and testosterone production.

Now, a new study suggests that the hormone might someday help regenerate damaged heart muscles.

The researchers said that previous research has concluded that the epicardium, a membrane found in the layers of the heart, can partially regenerate injured heart cells. In mammals, however, this process doesnt work independently but might if cells are reprogrammed.

Researchers noted that zebrafish produced oxytocin after their hearts were injured by extreme cold, leading to a response that promotes heart regeneration.

The heart possesses a population of cells, called epicardial cells, that reside in its outer layers, said Aitor Aguirre, Ph.D., one of the authors of the study and an assistant professor of biomedical engineering at the Institute for Quantitative Health Science and Engineering at Michigan State University.

After a massive cardiac injury, such as a heart attack, epicardial cells become epicardial stem cells and can then regenerate muscle, blood vessels, and other cardiac tissues, but their numbers are far too small for any long-lasting impact, he told Healthline.

What we have found in this study is that oxytocin induces the formation of these stem cells and promotes their expansion, increasing their efficiency in heart regeneration, Aguirre added. It is interesting because this demonstrates that the brain controls some regeneration, so there could be factors in addition to the oxytocin that promotes regeneration.

He noted that the most common role of oxytocin relates to bonding and pleasure, which suggests that being in a caring and loving environment might promote heart healing. You could say that the love hormone fixes broken hearts.

Zebrafish are known for their ability to regenerate cells throughout their body.

Past research has reported that these fish can regenerate organs, including the retina, spinal cord, parts of the brain, and certain internal organs. Experts say this makes them a good resource for studying this concept.

The researchers conducting the current study reported that within three days of the heart injury, the Zebrafish increased the expression of oxytocin in the brain by about 18-fold.

The oxytocin then traveled to the epicardium, which bound to the oxytocin receptor, triggering cells to develop new cells. These cells migrated to the myocardium and developed into cardiomyocytes, blood vessels, and other heart cells, replacing the injured ones.

Oxytocin had a similar effect on human cells in a laboratory. The scientists tested 15 neurohormones and they said oxytocin had the strongest effect on stimulating the regeneration of human cells.

Oxytocin is currently used during labor and delivery. It is used to begin or speed up contractions during labor and typically takes effect about 30 minutes after injection. It can also help to reduce bleeding after birth.

The risk of using oxytocin during labor is overstimulation of the uterus and causes it to contract too often, according to the American College of Obstetrics and Gynecology. This may lead to changes in the fetal heart rate.

While there are benefits to using oxytocin during labor and delivery, there are also risks. These risks and benefits will need to be considered as researchers look at the hormones potential use for stimulating heart regeneration.

Oxytocin, or a similar analog that stimulates its receptor, could conceivably be utilized to regenerate the heart in humans after acute or chronic injury, said Dr. Rigved Tadwalkar, a cardiologist at Providence Saint Johns Health Center in California.

The current study reveals the beneficial effects of oxytocin in zebrafish in vivo and on human tissue in vitro, Tadwalkar told Healthline. The findings suggest that the pathway involved in stimulating stem-like cells to the myocardium is preserved in humans, at least to a degree.

Unfortunately, oxytocin has a short half-life, meaning that it exists only briefly in human circulation, Tadwalkar added. However, we could take advantage of this beneficial signaling pathway in humans by creating drugs that are higher in potency or with longer half-lives.

Since we already use oxytocin clinically, this is not inconceivable, he noted. Even if the effects are limited, the benefit would be splendid in this population. For example, if oxytocin is shown to only have a preventative role, as opposed to a regenerative one, this would still be welcome, as to avert subsequent damage to the heart.

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How the 'Love Hormone' Oxytocin May Help Heal Heart Muscles - Healthline

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Neuron generation trajectories. Credit: BGI Genomics

Because of its distinctive and adorable look, the axolotl Ambystoma mexicanum is a popular pet. Unlike other metamorphosing salamanders, axolotls (pronounced ACK-suh-LAH-tuhl) never outgrow their larval, juvenile stage, a trait known as neoteny. Its also recognized for its ability to regenerate missing limbs and other tissues including the brain, spinal cord, tail, skin, limbs, liver, skeletal muscle, heart, upper and lower jaw, and ocular tissues like the retina, cornea, and lens.

Mammals, including humans, are almost incapable of rebuilding damaged tissue after a brain injury. Some species, such as fish and axolotls, on the other hand, may replenish wounded brain regions with new neurons.

Tissue types the axolotl can regenerate as shown in red. Credit: Debuque and Godwin, 2016

Brain regeneration necessitates the coordination of complex responses in a time and region-specific way. In a paper published on the cover of Science, BGI and its research partners used Stereo-seq technology to recreate the axolotl brain architecture throughout developing and regenerative processes at single-cell resolution. Examining the genes and cell types that enable axolotls to renew their brains might lead to better treatments for severe injuries and unlock human regeneration potential.

Cell regeneration images at seven different time points following an injury; the control image is on the left. Credit: BGI Genomics

The research team collected axolotl samples from six development stages and seven regeneration phases with corresponding spatiotemporal Stereo-seq data. The six developmental stages include:

Through the systematic study of cell types in various developmental stages, researchers found that during the early development stage neural stem cells located in the VZ region are difficult to distinguish between subtypes, and with specialized neural stem cell subtypes with spatial regional characteristics from adolescence, thus suggesting that various subtypes may have different functions during regeneration.

In the third part of the study, the researchers generated a group of spatial transcriptomic data of telencephalon sections that covered seven injury-induced regenerative stages. After 15 days, a new subtype of neural stem cells, reaEGC (reactive ependymoglial cells), appeared in the wound area.

Axolotl brain developmental and regeneration processes. Credit: BGI Genomics

Partial tissue connection appeared at the wound, and after 20 to 30 days, new tissue had been regenerated, but the cell type composition was significantly different from the non-injured tissue. The cell types and distribution in the damaged area did not return to the state of the non-injured tissue until 60 days post-injury.

The key neural stem cell subtype (reaEGC) involved in this process was derived from the activation and transformation of quiescent neural stem cell subtypes (wntEGC and sfrpEGC) near the wound after being stimulated by injury.

What are the similarities and differences between neuron formation during development and regeneration? Researchers discovered a similar pattern between development and regeneration, which is from neural stem cells to progenitor cells, subsequently into immature neurons and finally to mature neurons.

Spatial and temporal distribution of axolotl brain development. Credit: BGI Genomics

By comparing the molecular characteristics of the two processes, the researchers found that the neuron formation process is highly similar during regeneration and development, indicating that injury induces neural stem cells to transform themselves into a rejuvenated state of development to initiate the regeneration process.

Our team analyzed the important cell types in the process of axolotl brain regeneration, and tracked the changes in its spatial cell lineage, said Dr. Xiaoyu Wei, the first author of this paper and BGI-Research senior researcher. The spatiotemporal dynamics of key cell types revealed by Stereo-seq provide us a powerful tool to pave new research directions in life sciences.

Corresponding author Xun Xu, Director of Life Sciences at BGI-Research, noted that In nature, there are many self-regenerating species, and the mechanisms of regeneration are pretty diverse. With multi-omics methods, scientists around the world may work together more systematically.

Reference: Single-cell Stereo-seq reveals induced progenitor cells involved in axolotl brain regeneration by Xiaoyu Wei, Sulei Fu, Hanbo Li, Yang Liu, Shuai Wang, Weimin Feng, Yunzhi Yang, Xiawei Liu, Yan-Yun Zeng, Mengnan Cheng, Yiwei Lai, Xiaojie Qiu, Liang Wu, Nannan Zhang, Yujia Jiang, Jiangshan Xu, Xiaoshan Su, Cheng Peng, Lei Han, Wilson Pak-Kin Lou, Chuanyu Liu, Yue Yuan, Kailong Ma, Tao Yang, Xiangyu Pan, Shang Gao, Ao Chen, Miguel A. Esteban, Huanming Yang, Jian Wang, Guangyi Fan, Longqi Liu, Liang Chen, Xun Xu, Ji-Feng Fei and Ying Gu, 2 September 2022, Science.DOI: 10.1126/science.abp9444

This study has passed ethical reviews and follows the corresponding regulations and ethical guidelines.

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Unlocking the Mysteries of Brain Regeneration Groundbreaking Study Offers New Insight - SciTechDaily

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Chronic pain, a disease process that is so complex that we are only just beginning to understand its triggers, has recently been gaining recognition as a medical condition on its own. But how does living with chronic pain feel? And how do the body and brain deal with it?

Aching, dull, gnawing, burning, sharp, shooting, piercing

These are just some of the words people tend to use to describe their pain.

Now imagine you had to endure a bit of this every waking day until you dont know what its like to go about your day without this baseline of pain slowly depleting your mental and physical energy in the background.

That is the reality for many people who deal with chronic pain.

Some days may be great, some days bad; the signs may not always be visible and it may be an inward battle hidden behind gritted teeth and forced smiles.

But how does chronic pain become, well, chronic?

In the latest installment of our In Conversation podcast dedicated to Pain Awareness Month, Medical News Today dives into the science behind chronic pain with Dr. Hilary Guite and Dr. Tony L. Yaksh, professor of anesthesiology and pharmacology at the University of California, San Diego, as Joel Nelson, longtime psoriatic disease and arthritis patient and advocate, shares his personal journey with pain.

Chronic pain may often be dismissed as purely a symptom of a larger problem or not taken as seriously because it is not life threatening. However, the burden of chronic pain is not only personal but also societal.

Studies show that people with chronic pain may have difficulty in going about their daily lives and doing activities, as well as have poorer overall health. People with chronic pain may also have to deal with job insecurity or unemployment.

It wasnt until 2018 that the International Classification of Diseases (ICD) gave chronic pain its own code, in the preliminary version of the new ICD-11 coding system, paving way for its recognition and diagnosis.

According to the World Health Organization (WHO), chronic pain is now classified into two categories: chronic primary pain and chronic secondary pain.

Primary pain, according to this classification, refers to pain that is not caused by or cannot be explained by another medical condition. Some examples may be fibromyalgia or chronic primary low back pain.

Fibromyalgia [is] a condition that varies from person to person, but is a widespread pain condition affecting at least 4 to 5 regions of the body and lasts at least 3 months but usually longer. No other cause is found for the pain and it is, therefore, a type of primary chronic pain, Dr. Guite explained.

Secondary pain, on the other hand, is secondary to or caused by an underlying medical condition. Arthritis, cancer, or ulcerative colitis-related pain would fall within this umbrella.

[M]y chronic pain started around 10 years old. And [since] then, chronic pain has kind of been an intermittent part of my life right through to the present day, Joel Nelson told MNTs In Conversation.

Joel is now 38 years old, which means hes been living with chronic pain for a good few decades.

[M]y first experience with pain was [when] I got a pain in my hip; it was like a gravelly sort of burning feeling. And it just progressed; the more I used the joint, the [more it got] worse, it got to the point where I [was] sort of losing mobility, he said.

That was the point he decided to reach out for helpas most people do.

Joel said one word to describe his chronic pain is noise.

I always have described it as noise because on the days when that pain is intense, my ability to absorb other information, deal with multiple things at a time, its just gone, he said.

Living with my condition today, I think the most important takeaway about the experience is the fluidity of it. [U]ltimately, [my limits and mobility] can range from anything to where I can do more than walking, and I might be able to do a bit of running and cycling like I am currently, to next week I might be back on crutches. [A] lot of that is dictated by pain. So with arthritis, I get a lot of morning stiffness, but its the pain that limits my ability to do things. Joel Nelson

Likening it to a series of chapters, Joel said its not easy to anticipate what will happen next with his chronic pain.

Behind acute pain becoming chronic, scientists have found that a gateway receptor called Toll-like receptor 4 (TLR4) may be a controlling factor.

We know that under a tissue [or nerve] injury of various sorts that we can activate signaling that normally is associated with what we call innate immunity. And one of the mediators of that is something called the toll-like receptor and it turns out that while those are normally there to recognize the presence of foreign bugs, for example, E. coli, those bugs have in their cell membrane, something called lipopolysaccharide, or LPS. We dont have that normally in our system, but it comes from bacteria, said Dr. Yaksh.

Youre born with it, you dont have to develop it. Its there all the time. What weve come to find out over the last years [t]hat there are many products that your body releases that will [a]ctivate those very same toll-like receptors, he added.

Toll-like receptors may prime the central immune system for heightened states of pain. In response to harmful stimuli, stressors, or tissue injury, especially in the microbiome or the gastrointestinal tract, the body starts to release products from inflammatory cells.

When this happens, these products that are released from our own body can [a]ctivate these toll-like receptors, and theres [one] we call TLR4 [which] is present on inflammatory cells, and its also present on sensory neurons, he explained.

Dr. Yaksh said that activating TLR4 itself doesnt cause as much pain, but that it sets the nervous system up to become more reactive.

Coupled with this priming, if there are other stressors present at the timesuch as a bad diet or psychological distress, pointed out Dr. Guite this can set off a whole cascade that can fuel this transition to chronic pain.

[The activation of TLR4] sets up a whole series, a cascade in which there will be an increased expression of a large number of receptors and channels that are able to drive an enhanced response of the system. When this happens, you get this enhanced response downstream to the initial tissue injury. Its not so much that [it] causes the pain condition, it just sets the system up to be more reactive. Dr. Tony Yaksh

He said Joels situation fits within the notion that a person can transition from one type of pain to another.

[T]hat can be exacerbated by the stresses that are psychological which can exacerbate a pain state to one that may, in fact, have an underlying physiological component that we may not really understand, he added.

In Joels case, for example, Dr. Yaksh suggested it was likely that the stress (and joy) of becoming a father and all the other aspects played a role in what exacerbated Joels condition, and made it harder to keep the pain under control. He stressed that this did not make the pain any less real.

I think that probably there was this very strong, emotive component thats associated what Joels situation was, [] that the pain condition and the events that were associated with the psoriatic diagnosis and other aspects, perhaps, in fact, did establish the transition from one state to another [what] we call a transition or an acute to chronic, or the chronification of the pain state, he elaborated.

Theories so far suggest pain happens at the intersection of where the body meets the brain.

[Y]our comment about pain [being] in the brain is absolutely the correct way to think about it; the output function of anything comes from the higher centers, said Dr. Yaksh.

It all boils down to how the brain registers pain when there is tissue damage.

Pain is a crucial function for our survival; it is essentially a warning system that alerts our bodies that there is damage or illness to deal with. After an illness or injury, the nerves surrounding the area start sending signals up to the brain through the spinal cord, which encourages us to get help and stop further damage.

After the body sustains an injury, the damage to the bodys organs and tissues triggers an acute inflammatory response that involves immune cells, blood vessels, and other mediators. However, sometimes, even after this initial injury phase passes and the body heals, the nervous system may stay in this state of distress or reactivity.

When this happens, the body may become hypersensitive to pain. If this increased sensitivity is to heat or touch around the injured area, this is called peripheral sensitization.

[I]f I were to jam my finger, or if I were to develop, in Joels case, an event that leads to a local autoinflammation of the joint, then, in fact, that inflammation leads to the release of factors, which now sensitize the innervation of that joint, Dr. Yaksh elaborated.

Dr. Yaksh said this is something all people experience, regardless of whether it is chronic pain. He explained that after an injury, however, an innocuous activity such as wiggling ones finger can [become] extraordinarily noxious.

He described this as a sensitization generated by peripheral injury and inflammation, where this information is then relayed to the brain through the spinal cord.

The brain is now seeing what is otherwise an innocuous event, generating a signal that looks as if, as we would say, hell has frozen over, bad news is coming up the pipe. Dr. Tony Yaksh

However, sometimes this prolonged response to the initial injury may cause the lingering pain to be widespread, rather than localized to the injured area. This is called central sensitization.

[I]ts interesting in [Joels case], that you clearly have a peripheral issue, whether its the inflammation of a joint, inflammation of the skin, or changes in peripheral nerve function. And so not only do you get changes in joint morphology and things of that sort, but you actually get changes that lead to changes in the way that the information that goes into the spinal cord, and then to higher centers, Dr. Yaksh explained, and youve activated specific populations of sensory fibers that are normally activated only by severe injury.

[I]ts possible for that spinal cord, which is now, in a sense, organizing the input-output function from the periphery to the brain can become reorganized very much like if I were to take a radio and turn the volume upthe signal to the radio hasnt changed, but the volume gets louder. So, think of the spinal cord as a volume regulator. Dr. Tony Yaksh

And it says, bad news has happened. But we now know actually, that some of that input that comes up the same pathway [g]oes to areas of the brain that has nothing to do with where that pain [comes] fromonly that it is intense, he said.

These outputs that travel up the spinal cord inform the brain of where and how intense the pain is. One area these are processed in is the limbic system, or the old smell brain, said Dr. Yaksh.

These are areas of the brain that are, in fact, associated in humans with the input associated with emotionality, he added.

This stress can also modulate how pain is perceived by the body; it can cause muscles to tense or spasm, as well as lead to a rise in the levels of the hormone cortisol. This may cause inflammation and pain over time.

This can, in turn, can lead to sleeping problems, irritability, fatigue, and depression over time, creating a vicious cycle that adds to an already stressed nervous system, worsening the pain.

Although treatments for acute pain often involve taking various medications such as acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), or opioids, treatment and management strategies for chronic pain are quite limited.

[W]e started out this conversation by saying pain is in the brain. And your perceptions of what the world is about impact you very directly, and in a way that is actually experimentally definable, changes the way your brain reacts. So when I say pain is in the brain, I am not saying its, its any less real in any way, shape, or form. Its a real thing, said Dr. Yaksh.

We now teach medical students that, you know, just because you dont see the primary diagnosis as being a swollen joint doesnt mean the patient doesnt have something, he pointed out.

Dr. Yaksh said mindfulness is often used in therapy to treat or manage fibromyalgia. He said that this doesnt mean there is no physiological component of fibromyalgia and indeed, recent research has shown that it is very likely to be an autoimmune condition just as real as the presence of antibodies that define the presence of an arthritic joint, he said.

Mindfulness, in a way, can help the individual respond to the nature of the afferent traffic thats coming up the spinal cord; its not something you could become mindful enough to say have surgery done. But it might [t]ake the edge off of some of the things that are, in fact, driving this exaggerated response. Fibromyalgia is a perfect example. Dr. Tony Yaksh

[Mindfulness] doesnt make the pain state any less real [but it] demonstrates that changing the way you think about your pain condition [can] help you deal with that pain condition, he said.

Joel added that, from the perspective of someone with chronic pain, it is a journey to see how the brain and the body work together to maintain pain:

.[I]t is a really delicate conversation when you talk about pain and it residing in the brain and, as somebody whos gone full circle through that journey of being horrified when that was first suggested to going through pain management, and then understanding it so that I could process it better. It changed everything for me.

What the future holds for treating chronic pain currently remains unclear. However, hope is that drugs might be developed to impact receptors such as TLR4 in a way that might not result in the pain going from acute to chronic, and that our understanding of how psychological processes interact with the neuro-immune interface increases over time.

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In Conversation: How to understand chronic pain - Medical News Today

Spinal Cord Stem Cells Comments Off on In Conversation: How to understand chronic pain – Medical News Today | October 5th, 2022

ONE of the most aggressive types of cancer is looking more beatable thanks to an exciting breakthrough.

Patients with glioblastoma - a fast-growing type of cancer that affects the brain and spinal cord - tend to survive just 15 months from the moment of diagnosis.

1

And currently, few successful long-term treatments are available.

But scientists at the Keck School of Medicine of USC have made a discovery that may offer real hope.

The team found that circadian clock proteins - which control our natural rhythms, like when we wake up and when we fall asleep - could be involved in the growth of glioblastoma tumours.

These proteins may also explain why people often do not remain in remission after cancer treatment, and see their glioblastoma come back.

Keck researchers identified a small molecule drug, called SHP656, that could be used to target those clock proteins and treat the devastating disease.

In the vast majority of patients, the cancer returns. And when it returns, its resistant to chemotherapy and radiation, said Professor Steve Kay at Keck.

Kay and his team believe the disease often returns because of cancer stem cells that spread fast by hijacking the bodys circadian clock mechanisms.

But SHP656 could be used to put a stop to that.

This is a potent molecule thats very exciting to us in terms of its potential for deployment against glioblastoma, said Kay.

Clinical trials are now in motion and the team hopes to begin the next phase in glioblastoma patients within two to three years.

Glioblastomas are grade 4brain tumoursand are a type of glioma, one of the most common types of primary brain tumours.

The cancer begins in the brain and almost never spreads to other parts of the body.

However, its complexity makes it difficult to treat.

There are no known causes of glioblastoma making treatment even trickier.

The first line of treatment is surgery to try and cut the tumour out.

However, it's very difficult to remove the tumour without harming healthy parts of the brain.

Chemotherapy and radiation therapy can be helpful to stop the tumour cells growing and spreading.

But despite the high intensity of the treatment, the cancer usually recurs.

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New drug could cure aggressive brain cancer stopping tumours in their tracks... - The US Sun

Spinal Cord Stem Cells Comments Off on New drug could cure aggressive brain cancer stopping tumours in their tracks… – The US Sun | September 27th, 2022

Sep 17, 2022(Nanowerk News) Few human injuries are as catastrophic as those to the spine. An accident, disease or act of violence affecting the spine can result in poor function even paralysis almost anywhere in the body.The spinal column is enormously complex, with limited capacity for regeneration and any health implications are usually long-term and chronic.While there is no known way to repair a spinal cord injury (SCI), scientists may be on the cusp of some important breakthroughs. New approaches are being taken to reverse the nerve damage, with some researchers attempting to reshape the architecture of the spinal cord using materials engineered in the laboratory.Prof Paula Marques, material scientist at the University of Aveiro in Portugal and her colleagues, are seeking to mould a particular biomaterial into a scaffold that can replace damaged spinal tissue. This will create a working bridge over an injured area giving the brain an alternative pathway to communicate with the body.The hope is that, within the next decade, these biomaterials will result in radical new treatments for the 250-500 000 people who suffer a spinal cord injury around the world every year.Even a small improvement in treatment can lead to a big change to quality of life, said Prof Marques.The spinal column is enormously complex. (Image: CHUTTERSNAP via Unsplash)Nerve regenerationIn addition, the scaffold implant would support the regeneration of natural nerve cells, enabling the body eventually to resume its natural function unassisted.Prof Marques is the principal researcher of the NeuroStimSpinal project, an EIC Pathfinder project under Horizon 2020 focusing on graphene-based material combined with a protein-rich material derived from humans known as a 'decellularised extracellular matrix'. In the human body, an extracellular matrix provides the structure and support to living cells.This blend of matrix and graphene-based material creates a 3D structure that skilfully mimics the morphology of the native spinal cord. It will form the backbone as it were of the projects implant.Graphene shows excellent electrical properties, meaning a current can run along it a prerequisite for any material that might be employed to send electrical impulses along the spinal cord.Importantly, the scaffold is porous, meaning cells and spinal fluids can pass through it. Its also biocompatible, preventing rejection by the body, and biodegradable, allowing it to be programmed to degrade over time.Restoring functionProf Marques describes her work as disruptive and says the potential prize of restoring function to people with paralysis is huge.I see real hope, she said. My only frustration is that we cant move forward faster with this research spinal cord injury has such a big impact on human life.There are two main types of cells in nerve tissue: neurons, which transmit electrical impulses, and glial cells, which are non-conductive and provide a support system for the neurons.In lab experiments, the NeuroStimSpinal team which includes experts in material science, electronic engineering, physics and biology have found that when their scaffold is seeded with embryonic neural progenitor cells (cells that renew themselves and have the potential to develop into either neuronal or glial cells) and an electrical stimulus is applied, the blank stem cells successfully differentiate into a mixture of the two cell types.This is very encouraging, said Prof Marques. It shows that the scaffold can provide a good environment for nerve cell regrowth.Her group is one of just a handful around the world that has managed to make neural stem cells develop into new cell lineages in lab conditions.However, to date, no such success has been achieved in live animals. Prof Marques wants her next round of experiments to set SCI research on a new course.In the months ahead, her team will transplant miniature versions of their scaffold into rats. An electric current will be applied to the implant through a control unit inserted under the animals skin to accelerate tissue regrowth. If these experiments show regeneration of the animals spinal cord is possible with the scaffold in place, Prof Marques will apply for fresh funding to take her work to the next level.I hope we can contribute with our scientific knowledge to take a step forward towards SCI repair, she said.Catastrophic strokeA stroke is another catastrophic life event that can result in damage to the nervous system. Strokes, besides being the number two cause of death worldwide, are the third-leading cause of disability-adjusted life years (DALY), a metric used to assess the burden of death and disease.Scientists have yet to find a way to replace the dead brain cells that result from a clot blocking the flow of blood and oxygen to the brain, but they are starting to exploit the latest technology such as advances in virtual reality (VR) to help patients recover from some of the long-term consequences.After a stroke, hands can become stiff due to disrupted connections between the brain and the hand muscles. This spasticity can make it hard, almost impossible, to straighten fingers or grasp an item.These hand impairments can severely impact daily life, said Dr Joseph Galea, a researcher in motor neuroscience at the University of Birmingham in the UK.Though theres been a lot of focus on improving large, reaching-arm movements after a stroke, theres been little work on improving hand functionality.Dr Galea wants to improve hand-movement recovery through the ImpHandRehab project. With funding from the European Research Council, this project asks stroke patients to perform tasks involving increasingly complex hand movements a form of rehabilitation that will ultimately improve dexterity and quality of life. Users perform their tasks wearing a VR headset paired with affordable, off-the-shelf motion-capture gloves.Demonstration of VR training for stroke treatments. (Video: Joseph Galea)What motivates users to stick to their tasks?Immersive VRGaming, explained Dr Galea. Weve developed two really immersive VR games that reward people for doing better and better at something like popping a balloon or controlling a submarine. Weve noticed that the more points or coins are at stake, the harder a person will try and the better theyll perform.Best of all, he and his colleagues have found that after a game has been played for a prolonged period of time, the improved hand performance persists even when the VR headset is removed.We envisage our solution being used by patients at home, said Dr Galea. It would be complementary to traditional rehab techniques.

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Rehabilitating spinal cord injury and stroke with graphene and gaming - Nanowerk

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The induced pluripotent stem cells production market has been estimated to reach a CAGR of 8.0% in the foreseeable years from 2021to 2031.

The revenue generation opportunities in the induced pluripotent stem cells production market are attributed to an increased number of R & D activities by numerous organizations and companies to explore iPSCs potential in cell therapeutics that are targeted to treat various diseases.

Induced pluripotent stem cells come with various advantages compared to ESCs (Embryonic Stem Cells), for instance, maximum flexibility in research applications that are based on cells and avoiding the ethical implication associated to stem cells. These advantages of the industry services are likely to contribute to expansion opportunities in the induced pluripotent stem cell production market in the following years.

Increasing uses of iPSCs and robust pipelines for the cell therapeutics that are derived from iPSC have also been projected to serve as revenue generators in the induced pluripotent stem cells production market in the coming years.

In recent years, regenerative medicines are gaining popularity across the globe. In addition to this, iPSCs have been used at an increased rate to regenerate tissue-specific cells to transplant to patients who are experiencing various injuries. The researchers have also been taking an interest to use iPSCs for ex-vivo expansion of different blood components. These factors are likely to contribute to growth opportunities in the induced pluripotent stem cells production market.

Global Induced Pluripotent Stem Cells Market: Overview

Induced pluripotent stem cells (iPSCs) hold profound potential in replacing the use of embryonic stem cells (ESCs) as important tool for drug discovery and development, disease modeling, and transplantation medicine. Advent of new approaches in reprogramming of somatic cells to produce iPSCs have considerably advanced stem cell research, and hence the induced pluripotent stem cells market. The iPSC technology has shown potential for disease modeling and gene therapy in various areas of regenerative medicine. Notable candidates are Parkinsons disease, spinal cord trauma, myocardial infarction, diabetes, leukemia, and heart ailments.

Over the past few years, researchers have come out with several clinically important changes in reprogramming process; a case in point is silencing retroviruses in the human genome. Molecular mechanisms that underlie reprogramming have gained better understanding. However, the tools based on this growing understanding are still in nascent stage. Several factors affect the efficiency of reprogramming, most notably chromosomal instability and tumor expression. These have hindered researchers to utilize the full therapeutic potential of iPSCs, reflecting an unmet need, and hence, a vast potential in the induced pluripotent stemcellsmarket.

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Global Induced Pluripotent Stem Cells Market: Growth Dynamics

The growing application of induced pluripotent stem cells in generating patient-specific stem cells for drug development and human disease models is a key dynamic shaping their demands. Growing focus on personalized regenerative cell therapies among medical researchers and healthcare proponents in various countries have catalyzed their scope of induced pluripotent stem cells market. Advent of new methods to induce safe reprogramming of cells have helped biotechnology companies improve the clinical safety and efficacy of the prevailing stem cells therapies. The relentless pursuit of alternative source of cell types for regenerative therapies has led industry players and the research fraternity to pin hopes on iPSCs to generate potentially a wide range of human cell types with therapeutic potential.

Advances pertaining to better utilizing of retrovirus and lentivirus as reprogramming transcription factors in recent years have expanded the avenue for players in the induced pluripotent stem cells market. Increasing focus on decreasing the clinical difference between ESCs and iPSCs in all its entirety has shaped current research in iPSC technologies, thus unlocking new, exciting potential for biotechnology and pharmaceutical industries.

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Global Induced Pluripotent Stem Cells Market: Notable Development

Over the past few years, fast emerging markets in the global induced pluripotent stem cells are seeing the advent of patents that unveil new techniques for reprogramming of adult cells to reach embryonic stage. Particularly, the idea that these pluripotent stem cells can be made to form any cells in the body has galvanized companies to test their potential in human cell lines. Also, a few biotech companies have intensified their research efforts to improve the safety of and reduce the risk of genetic aberrations in their approved human cell lines. Recently, this has seen the form of collaborative efforts among them.

Lineage Cell Therapeutics and AgeX Therapeutics have in December 2019 announced that they have applied for a patent for a new method for generating iPSCs. These are based on NIH-approved human cell lines, and have been undergoing clinical-stage programs in the treatment of dry macular degeneration and spinal cord injuries. The companies claim to include multiple techniques for reprogramming of animal somatic cells.

Such initiatives by biotech companies are expected to impart a solid push to the evolution of the induced pluripotent stem cells.

Global Induced Pluripotent Stem Cells Market: Regional Assessment

North America is one of the regions attracting colossal research funding and industry investments in induced pluripotent stem cells technologies. Continuous efforts of players to generate immune-matched supply of pluripotent cells to be used in disease modelling has been a key accelerator for growth. Meanwhile, Asia Pacific has also been showing a promising potential in the expansion of the prospects of the market. The rising number of programs for expanding stem cell-based therapy is opening new avenues in the market.

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Along with studying the opportunities necessary for growth, threats are also an important aspect to look upon for the companies and stakeholders in a specific sector. TMR Research studies every negative aspect that will hinder the growth of a specific area of business and includes it in the report. The stakeholders and CXOs will have the benefit of assessing the threat and take the necessary steps to prevent the hindrance caused due to the threats.

Accurate Trend Analysis

Keeping up with the latest trends is crucial in any business or sector. While stakeholders are aware of the trends that are on the surface, TMR Researchers find trends that are deeply entrenched in the particular market or sector. The reports are constantly updated with the latest trends so that the stakeholders and CXOs can derive benefits from the trends and generate good revenues.

Regional Assessment

Demography forms an important part of the growth pattern of all the markets. Diving deep into the demographics enables maximum output from specific areas. The TMR Research team assesses every region and picks out the vital points that have a large impact on the growth of a market.

Industrial Analogy

The analysts at TMR Research conduct an all-round analysis on the competitive landscape of the market. The observations recorded by the analysts are added to the reports so that every stakeholder gets a glimpse of the competitive scenario and frame their business plans according to the situation.

COVID-19 Impact

The COVID-19 outbreak has changed the growth projections of numerous sectors and businesses. The analysts at TMR Research have conducted a conscientious survey on the markets after the pandemic struck. The analysts have put forth their brilliant and well-researched opinions in the report. The opinions will help the stakeholders to plan their strategy accordingly.

The reports offer answers to the top 7 questions that revolve around the growth of the market

About TMR Research

TMR Research is a premier provider of customized market research and consulting services to business entities keen on succeeding in todays supercharged economic climate. Armed with an experienced, dedicated, and dynamic team of analysts, we are redefining the way our clients conduct business by providing them with authoritative and trusted research studies in tune with the latest methodologies and market trends.

Contact:

Rohit Bhisey

TMR Research,

3739 Balboa St # 1097,

San Francisco, CA 94121

United States

Tel: +1-415-520-1050

Visit Site: https://www.tmrresearch.com/

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Induced Pluripotent Stem Cells Market Reaches at a CAGR of 8.0% in the Forecast Periods [2021-2031] - BioSpace

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