Tuesday 31 January 2023

Diabetes reversed in mice with genetically edited stem cells derived from patients

 Using induced pluripotent stem cells produced from the skin of a patient with a rare, genetic form of insulin-dependent diabetes called Wolfram syndrome, researchers transformed the human stem cells into insulin-producing cells and used the gene-editing tool CRISPR-Cas9 to correct a genetic defect that had caused the syndrome. They then implanted the cells into lab mice and cured the unrelenting diabetes in those mice.

The findings, from researchers at Washington University School of Medicine in St. Louis, suggest the CRISPR-Cas9 technique may hold promise as a treatment for diabetes, particularly the forms caused by a single gene mutation, and it also may be useful one day in some patients with the more common forms of diabetes, such as type 1 and type 2.

The study is published online April 22 in the journal Science Translational Medicine.

Patients with Wolfram syndrome develop diabetes during childhood or adolescence and quickly require insulin-replacement therapy, requiring insulin injections multiple times each day. Most go on to develop problems with vision and balance, as well as other issues, and in many patients, the syndrome contributes to an early death.

"This is the first time CRISPR has been used to fix a patient's diabetes-causing genetic defect and successfully reverse diabetes," said co-senior investigator Jeffrey R. Millman, PhD, an assistant professor of medicine and of biomedical engineering at Washington University. "For this study, we used cells from a patient with Wolfram syndrome because, conceptually, we knew it would be easier to correct a defect caused by a single gene. But we see this as a stepping stone toward applying gene therapy to a broader population of patients with diabetes."

Wolfram syndrome is caused by mutations to a single gene, providing the researchers an opportunity to determine whether combining stem cell technology with CRISPR to correct the genetic error also might correct the diabetes caused by the mutation.

A few years ago, Millman and his colleagues discovered how to convert human stem cells into pancreatic beta cells. When such cells encounter blood sugar, they secrete insulin. Recently, those same researchers developed a new technique to more efficiently convert human stem cells into beta cells that are considerably better at controlling blood sugar.

In this study, they took the additional steps of deriving these cells from patients and using the CRISPR-Cas9 gene-editing tool on those cells to correct a mutation to the gene that causes Wolfram syndrome (WFS1). Then, the researchers compared the gene-edited cells to insulin-secreting beta cells from the same batch of stem cells that had not undergone editing with CRISPR.

In the test tube and in mice with a severe form of diabetes, the newly grown beta cells that were edited with CRISPR more efficiently secreted insulin in response to glucose. Diabetes disappeared quickly in mice with the CRISPR-edited cells implanted beneath the skin, and the animals' blood sugar levels remained in normal range for the entire six months they were monitored. Animals receiving unedited beta cells remained diabetic. Their newly implanted beta cells could produce insulin, just not enough to reverse their diabetes.

Source: ScienceDaily

Monday 30 January 2023

Stem cell-based biomaterial can help regenerate tissue associated with low back pain and spinal issues

 Many people have experienced the struggles of dealing with low back pain. A common cause of this pain is degeneration of intervertebral disks (IVDs), which are located between the vertebrae and help give the spinal column its flexibility. Thus, IVD degeneration can lead to more serious conditions such as spinal deformity. In a recent article published in Biomaterials, a team led by researchers at Osaka University and Kyoto University demonstrated that using cartilage tissue derived from human stem cells could help prevent the loss of functionality from IVD degeneration.

It is believed that IVD degeneration originates in the nucleus pulposus (NP), which is composed of NP cells that produce the surrounding extracellular matrix (ECM). The ECM fosters an environment that is supportive of the NP cells, and also helps give the NP its mechanical elasticity. Previous work on treatment methods utilizing native viable NP cells that help produce the ECM has been promising, but these restorative effects are lost in advanced stages of degeneration where these cells are no longer present. Therefore, the Osaka University and Kyoto University group aimed to establish a tissue-engineered implant that contains the necessary cells to create and maintain the ECM in the NP.

"The ECM of the NP is a network of collagen that acts as scaffolding for other important proteins. Interestingly, this composition is similar to the ECM of articular cartilage," says Takashi Kamatani, lead author of the study. "Thus, we hypothesized that cell types that can produce and support cartilage could be useful for treating IVD degeneration."

The researchers used induced pluripotent stem cells (iPSCs) that can become different cell types, because they do not have the growth and division limits of native NP cells. Additionally, they can be induced to become chondrocytes, which are cells that produce and maintain cartilage. This method had been successfully used to create repair tissue when implanted into certain animals with articular cartilage defects. Here, they developed human iPSC-derived cartilaginous tissue (hiPS-Cart) for implantation into lab rats that had the NP removed from the IVD as a model of IVD degeneration.

"The hiPS-Cart implanted in these rats was able to survive and be maintained," explains senior author, Noriyuki Tsumaki. "IVD and vertebral bone degeneration were prevented. We also assessed the mechanics and found that hiPS-Cart was able to revert these properties to similar levels observed in the control rats."

The team also examined the gene expression profile of hiPS-Cart six weeks after implantation. They found characteristics consistent with chondrocyte-like NP cells and not the other NP cell type (called notochordal). This suggested that these chondrocyte-like cells alone were sufficient to restore the NP functionality.

Source: ScienceDaily

Sunday 29 January 2023

This groundbreaking biomaterial heals tissues from the inside out

 A new biomaterial that can be injected intravenously, reduces inflammation in tissue and promotes cell and tissue repair. The biomaterial was tested and proven effective in treating tissue damage caused by heart attacks in both rodent and large animal models. Researchers also provided proof of concept in a rodent model that the biomaterial could be beneficial to patients with traumatic brain injury and pulmonary arterial hypertension."This biomaterial allows for treating damaged tissue from the inside out," said Karen Christman, a professor of bioengineering at the University of California San Diego, and the lead researcher on the team that developed the material. "It's a new approach to regenerative engineering."

A study on the safety and efficacy of the biomaterial in human subjects could start within one to two years, Christman added. The team, which brings together bioengineers and physicians, presented their findings in the Dec. 29 issue of Nature Biomedical Engineering.

There are an estimated 785,000 new heart attack cases in the United States each year, and there is no established treatment for repairing the resulting damage to cardiac tissue. After a heart attack, scar tissue develops, which diminishes muscle function and can lead to congestive heart failure.

"Coronary artery disease, acute myocardial infarction, and congestive heart failure continue to be the most burdensome public health problems affecting our society today," said Dr. Ryan R. Reeves, a physician in the UC San Diego Division of Cardiovascular Medicine. "As an interventional cardiologist, who treats patients with coronary artery disease and congestive heart failure on a daily basis, I would love to have another therapy to improve patient outcomes and reduce debilitating symptoms."

In previous studies, the team led by Christman developed a hydrogel made from the natural scaffolding of cardiac muscle tissue, also known as the extracellular matrix (ECM), that can be injected into damaged heart muscle tissue via a catheter. The gel forms a scaffold in damaged areas of the heart, encouraging new cell growth and repair. Results from a successful phase 1 human clinical trial were reported in fall 2019. But because it needs to be injected directly into heart muscle, it can only be used a week or more after a heart attack -- sooner would risk causing damage because of the needle-based injection procedure.

The team wanted to develop a treatment that could be administered immediately after a heart attack. This meant developing a biomaterial that could be infused into a blood vessel in the heart at the same time as other treatments such as angioplasty or a stent, or injected intravenously.

"We sought to design a biomaterial therapy that could be delivered to difficult-to-access organs and tissues, and we came up with the method to take advantage of the bloodstream -- the vessels that already supply blood to these organs and tissues," said Martin Spang, the paper's first author, who earned his Ph.D. in Christman's group in the Shu Chien-Gene Lay Department of Bioengineering.

One advantage of the new biomaterial is that it gets evenly distributed throughout damaged tissue, because it's infused or injected intravenously. By contrast, hydrogel injected via a catheter remains in specific locations and doesn't spread out.

How the biomaterial is made

Researchers in Christman's lab started with the hydrogel they developed, which was proven to be compatible with blood injections as part of safety trials. But the particle size in the hydrogel was too big to target leaky blood vessels. Spang, then a Ph.D. student in Christman's lab, solved this issue by putting the liquid precursor of the hydrogel through a centrifuge, which allowed for sifting out bigger particles and keeping only nano-sized particles. The resulting material was put through dialysis and sterile filtering before being freeze dried. Adding sterile water to the final powder results in a biomaterial that can be injected intravenously or infused into a coronary artery in the heart.

How it works

Researchers then tested the biomaterial on a rodent model of heart attacks. They expected the material to pass through the blood vessels and into the tissue because gaps develop between endothelial cells in blood vessels after a heart attack.

But something else happened. The biomaterial bound to those cells, closing the gaps and accelerating healing of the blood vessels, reducing inflammation as a result. Researchers tested the biomaterial in a porcine model of heart attack as well, with similar results.

The team also successfully tested the hypothesis that the same biomaterial could help target other types of inflammation in rat models of traumatic brain injury and pulmonary arterial hypertension. Christman's lab will undertake several preclinical studies for these conditions.

Next steps

"While the majority of work in this study involved the heart, the possibilities of treating other difficult-to-access organs and tissues can open up the field of biomaterials/tissue engineering into treating new diseases," Spang said.

Meanwhile, Christman along with Ventrix Bio, Inc., a startup she cofounded, are planning to ask for authorization from the FDA to conduct a study in humans of the new biomaterial's applications for heart conditions. This means that human clinical trials begin in be one or two years.

Source: ScienceDaily

What to know about diabetic neuropathy.

Diabetic neuropathy is a complication of diabetes that results in damage to the nervous system. It is a progressive disease, and symptoms get worse over time.

Neuropathy happens when high levels of fats or sugar in the blood damage the nerves in the body. It can affect virtually any nerve in the body, with a wide range of symptoms.

Nerves are essential to how the body works. They enable peopleTrusted Source to move, send messages about how things feel, and control automatic functions, such as breathing.

There are several types. Some involve the peripheral nerves, while others damage the nerves that supply the internal organs, such as the heart, the bladder, and the gut. In this way, it can affect many body functions.

Between one-third and a halfTrusted Source of people with diabetes have neuropathy, according to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

In this article, we explore the different types, effects, and risks of diabetic neuropathy.

Types

Four main types of neuropathy can impact on the nervous system, including:

  • Peripheral symmetric neuropathy: This affects the feet and hands. It is the most common form of diabetic neuropathy.
  • Autonomic neuropathy: This occurs in the nerves that control involuntary functions of the body, such as digestion, urination, or heart rate.
  • Thoracic and lumbar root, or proximal, neuropathy: This damages nerves along a specific distribution in the body, such as the chest wall or legs.
  • Mononeuropathies: These can affect any individual nerve.

    The symptoms of neuropathy depend on the type and the nerves involved.

    The signs and symptoms of diabetic neuropathy usually take several years to appear. Signs and symptoms will depend on which type of neuropathy and nerves it affects.

    Peripheral neuropathy

    The symptoms of peripheral neuropathy include:

    • numbness, pain, tingling, and burning sensations starting in the toes and fingers then continuing up the legs or arms
    • loss of muscle tone in the hands and feet
    • not being able to feel heat, cold, or physical injury
    • loss of balance
    • Charcot’s joint, in which a joint breaks down because of nerve issues, often in the feet

    Peripheral neuropathy that affects the feet can make it difficult for a person to stand and walk. It can increase the risk of falling.

    When a person cannot feel heat, cold or injury, this can lead to new problems.

    For example, a blister on the foot can become ulcerated because the person did not feel pain in the early stages. As the infection progresses, gangrene can develop.

    Eventually, amputation may be necessary.

    Autonomic neuropathy

    The effects of autonomic neuropathy include:

    • heartburn and bloating
    • nausea, constipation or diarrhea
    • hypoglycemic unawareness, in which a person does not feel the effects of low sugar levels
    • difficulties speaking or swallowing
    • feeling full after eating small amounts of food
    • vomiting several hours after eating
    • orthostatic hypotension, or feeling light-headed and dizzy when standing up
    • a faster heart rate than normal
    • excessive sweating, even in cool temperatures or while at rest
    • bladder problems, for example, difficulty emptying the bladder completely when urinating, leading to incontinence
    • sexual dysfunction in men and women
    • dysesthesia, or a distorted sense of touch
    • significant drooping of the face and eyelids
    • muscle contractions and weakness

    Other types

    There are many types of neuropathy.

    Proximal neuropathy can lead to pain in the lower body, often on one side, and weakness in the legs.

    Symptoms of focal neuropathy can vary widely, depending on the nerve affected. Focal neuropathy and cranial neuropathy can both lead to visual disturbances, such as double vision.

    People with diabetic neuropathy often do not realize they have it until the symptoms are more advanced.

    Not all of the symptoms of peripheral neuropathy are visible, but people should be aware of any wounds on their feet

    Medications

    Physical therapy

    Physical therapy, used in combination with medications, might help relieve pain and reduce the risk of dependency on opioids.

    It may also help alleviate:

    • burning and tingling sensations in the legs and feet
    • muscle cramps
    • muscle weakness
    • sexual dysfunction

    Electrical nerve stimulation is a painless type of physical therapy that might help to reduce feelings of stiffness and enhance the healing of foot ulcers.

    Gait training involves relearning how to walk. It helps to prevent and stabilize foot complications, such as ulcers and injury. This type of physical re-education is crucial for people using prosthesis after losing limbs if diabetic neuropathy leads to an amputation.

    A good physical therapist will ensure that exercises for people with diabetic neuropathy do not hurt the feet, which can be sensitive.

    Other therapies include devices that a person can use to keep painful or sensitive extremities from touching the bed or chair.

    A chiropractor, massage therapist, or osteopath can carry out regular massages or manual therapy to stretch the muscles. Massage can inhibit muscle contractions, spasms, and atrophy due to poor blood supply.

    Specific exercises, such as swimming or aerobics, can help an individual develop and maintain muscle strength and reduce the loss of muscle mass.

    Therapeutic ultrasound is another type of physical therapy that uses very high-frequency sound waves to stimulate the tissue beneath the skin. This can help some people to regain sensitivity in their feet.

    Complications

    Diabetic neuropathy can contribute to a number of high-risk complications, ranging from heart rate changes to visual disturbances.

    Possible complications include losing sensation in the feet.

    This can lead to an inability to feel cuts or sores, and infection might occur as a result. Untreated infection in a limb can result in the need for amputation.

    Severe bladder and kidney infections might also occur, causing health problems.

    To prevent the complications of diabetic peripheral neuropathy, good foot care is essential.

    People with the condition should inspect their feet every day for injuries or sores.

    Smoking also increases the risk of foot problems in people with certain types of diabetic neuropathy. A podiatrist can help with foot care, and a healthcare provider can give advice on quitting smoking.

    Q:

    A:

    The best way to minimize diabetic neuropathy is by maintaining good blood sugar control and regular foot care. If you take Metformin for a long time, which is a commonly used medication in the treatment of type 2 diabetes, consider having a Vitamin B12 level checked as well, as Metformin can lower the B12 level which can also cause neuropathy.

    Source - Medical News Today


    Trusted Source

    Saturday 28 January 2023

    How can diabetes affect the feet?


    Diabetes, especially poorly controlled diabetes, can cause nerve damage and poor circulation. This can lead to foot ulcers, blisters, pain, and foot infections.

    In some cases, the damage can be severe. Infections in the feet can spread, damaging other organs and even becoming life threatening. Severe foot infections may mean a doctor has to amputate the foot.

    While most people with diabetes do not develop severe foot complications, diabetes remains a leading cause of amputations.

    Diabetes is usually caused byTrusted Source insulin deficiency (type 1 diabetes) or insulin resistance (type 2 diabetes). Insulin is an essential hormone responsible for helping cells absorb sugar from the blood to use for energy.

    When this process does not work correctly, sugar remains circulating in the blood, causing health problems.

    Prolonged periods of high sugar levels in the blood can cause nerve damage and circulation problems, which can injure the feet.

    In this article, we look at foot problems that can occur in people with unmanaged or poorly managed diabetes and discuss how to prevent and manage these effects.

    Diabetic neuropathy

    People with diabetes have a higher risk of peripheral vascular disease (PVD)Trusted Source, especially if they do not take their medication or have difficulty controlling blood sugar. PVD occurs when fatty deposits narrow the blood vessels, reducing circulation.

    PVD tends to affect blood vessels leading to and from the extremities, such as the hands and feet, reducing blood flow to both. Reduced blood flow can lead to pain, infection, and wounds that heal slowly.

    Over time, peripheral vascular disease can cause nerve damage that leads to numbnessTrusted Source in the feet. This can make it hard for people with diabetes to feel sensations in their extremities. High blood sugar also damages the nerves and interferes with their ability to send signals.

    The condition also makes it difficult for a person with diabetes to feel irritation, soreness, or infection in the feet. A person may not notice when their shoes are rubbing. This lack of sensation can increase the risk of cuts, sores, and blisters. It can also delay treatment for an infection, since a person may not realize they have one.

    Blisters

    Diabetic ulcers

    Diabetic calluses

    Foot infections

    Amputation

    Death

    Nonsurgical treatment

    Surgical treatment

    • Preventing foot problems is essential for people who have diabetes. Keeping feet healthy is critical, and a person should be vigilant about foot hygiene. An individual can take the following steps:

      • Check the feet each day: Examine the feet daily or ask someone to check for any changes or injuries.
      • Wash the feet daily: Keep the feet clean to prevent infections.
      • Wear supportive shoes and socks: Protect the feet in socks and shoes at all times. A podiatrist may recommend special shoes to help prevent deformities. Do not apply socks so tightly that they restrict blood flow.
      • Promote blood flow to the feet: Put the feet up when sitting, wiggle the toes periodically, and get enough exercise. These actions help promote healthy blood flow to the feet.
      • Trim nails carefully: Trim toenails straight across and keep them short. Rounded nails can grow inward, leading to infection.
      • Care for corns and bunions: Treat corns and bunions carefully. Never shave corns, as this increases the risk of infection.
      • Protect feet from extreme temperatures: Exposure to extreme hot and cold can damage the feet of people with diabetes.
      • Receive regular examinations on the feet: Regular examinations by a doctor are key to preventing infections, amputations, and severe deformities.
      • Control blood sugar: Uncontrolled blood sugars increase the risk of podiatric complications from diabetes.
      • Avoid smoking: Smoking adversely affects blood flow to the tissues, making foot problems worse in people with diabetes.