INTERNATIONAL STEM CELL CORP MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS (form 10-K)  Marketscreener.com

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The body is always in a state of change. In particular, the cells in your skin are constantly replacing themselves.

The skin does this through the process of regeneration and repair.

On a cellular level, the skin cells are constantly shedding, revealing fresh, newly grown skin cells underneath. This is why scars and blemishes may fade a bit with time.

Understanding the science behind your skins life cycle can help you to take care of your skin as it goes through the regeneration process. It can also help you boost your skins natural regeneration process and give you a fresh glow.

Heres what the skin care experts have to say about how to speed up skin regeneration.

According to 2015 research, skin regeneration refers to the complete replacement of damaged tissue with new tissue. Skin repair refers to the continued healing process of existing tissue. Skin regeneration isnt usually associated with scar tissue.

The research goes on to say that skin regeneration can happen in two ways:

Skin regeneration is a natural physical process that occurs on a cellular level.

The epidermis cells, or top layers of skin, continuously replace themselves, explains Laura Chacon-Garbato, a licensed esthetician and director of education at Herbalife. This process of renewal is the process of shedding the epidermis.

In other words, skin regeneration is a constant renewal of cells.

According to a 2010 review, the epidermis is maintained by stem cells in the lowest layer of the skin. These epidermal stem cells generate daughter cells that move upward toward the surface of the skin.

During this journey, cells that produce keratin undergo a series of biochemical and morphological changes that result in the formation of the various layers of the skin.

This gives skin a young, healthy glow, adds Jennifer Hurtikant, chief science officer at Prime Matter Labs.

The same study mentioned above estimated that the epidermis turns over every 40 to 56 days on average.

When were young, the process of exfoliation happens naturally, but as we age this process is altered and slows down, Chacon-Garbato says.

An older 2006 study notes that the usual 28-day turnover time for skin increases approximately 30 percent to 50 percent by age 80.

For people over 50 years old, Chacon-Garbato says, the process can take as long as 84 days.

The effects of the slowdown cause buildup and an excess of dead skin cells that can make the skin look tired, dull, and opaque, she says.

Throughout this process, several things occur on a cellular level.

First, new skin cells are formed deep in the epidermis.

Then, as the skin cells mature and die on the upper layer of the epidermis, they naturally fall away.

If you have a cut or burn, you may be left with a scar.

This is because fibroblasts in scar tissue form collagen differently than in regular tissue. As a result, its thicker and less flexible than regular skin tissue.

However, by improving skin regeneration, you may notice that scars gradually fade away as fresh, healthy skin tissue forms beneath them.

As you get older, skin regeneration slows down. This leaves an accumulation of dead skin cells on the upper layer of the skin.

By boosting the natural regeneration process, you can help the skin look fresh and feel elastic, even as you age.

Making healthy choices can help to keep the skin regeneration process functioning optimally.

Hurtikant suggests:

There are two types of aging, cellular or intrinsic aging and environmental or extrinsic aging.

Intrinsic aging is a genetically predetermined process that occurs naturally, but may increase with stress. Extrinsic aging is a result of outside factors, like where you live and your lifestyle habits.

Stress causes intrinsic aging and the environment causes extrinsic aging, Hurtikant says.

Chacon-Garbato recommends eating plenty of protein, such as:

Proteins are essential for tissue repair and the construction of new tissue, she says. Cells need protein to maintain their life, so the body uses protein to replace worn-out or dead skin cells.

In addition, favor foods that are high in antioxidants, like:

Including antioxidants in your diet may help improve the glow and luster of the skin.

Specific skin care products can also help improve the natural cell turnover process, hydrate the skin, and get rid of built-up dead skin cells. Look for ingredients like:

Use products with vitamin B3, Chacon-Garbato suggests. Its a necessary component of cell metabolism, also known as niacinamide, and is required for many skin processes that help maintain healthy-looking skin.

She also suggests using antioxidants such as vitamin C and E to prevent cellular damage from free radicals.

Try Swisse Beauty Skin Regeneration+, an oral supplement with ALA, and Musely FaceRx Anti-Aging Night Cream with tretinoin, hyaluronic acid, and niacinamide.

These natural remedies may help boost your skins health and promote the skin regeneration process:

A 2022 study found that several plant extracts, including papaya, showed antioxidant, and antiwrinkle effects. Extracts that used ethanol as a cosolvent showed greater effects.

A 2018 review found that jojoba, rosehip, and coconut oil may help with skin barrier repair, wound healing, antioxidant effects, and antiaging.

A 2010 study noted that orange peel extract could provide useful protection against or alleviation of UV damage.

You can look for natural skin care products that contain these ingredients.

Citrus can increase photosensitivity, or sensitivity to light. Use caution when applying citrus in any form to the skin by avoiding direct sun exposure and using sun protection. Never apply citrus oils directly to the skin.

If you want to exfoliate a little deeper, a dermatologist may be able to offer a more intensive skin resurfacing procedure to kick-start skin rejuvenation. Make sure you find a dermatologist who is board certified.

Chacon-Garbato suggests:

However, she notes, theres no one-size-fits-all for the skin, so its important to check with your dermatologist to help define the best approach for the results you want to achieve.

Want to know more? Get the FAQs below.

Aloe vera encourages cell diversity and helps keep the skin well hydrated and protected.

According to a 2020 study, it also boasts natural antioxidant and anti-inflammatory properties.

Aloe vera is an excellent ingredient to use daily because its well known for its revitalizing and calming properties, Chacon-Garbato says. Its also a hugely effective hydrator and helps to minimize skin dryness.

She notes that its been used for centuries for beauty because of its many benefits, including delivering moisture directly to the tissue and helping prevent water loss due to evaporation.

Hurtikant adds that while aloe vera is great for boosting regeneration, there are other ingredients to try too.

Trending ingredients for skin regeneration are derivatives of algae and mushrooms, and hyaluronic acid, she says.

There are plenty of skin care products that have been shown to improve the appearance of aging in the skin by speeding up the natural skin regeneration process.

One highly rated product is Musely FaceRx Anti-Aging Night Cream, which includes active ingredients such as tretinoin (Retin-A), niacinamide, and hyaluronic acid.

These three ingredients are all excellent for encouraging exfoliation. Keep an eye out for them on the ingredients list when youre looking for good creams to promote regeneration.

For most adults under 50 years old, the cycle lasts between 28 and 42 days. For adults over 50 years old, this may increase to up to 84 days, though the number varies.

The time it takes for your skin to complete the skin regeneration cycle depends on a range of factors, including:

There are a range of ways to improve skin regeneration.

Simple lifestyle changes like exercise and increased hydration can keep the process working properly.

Skin creams that include exfoliating ingredients can also help to get rid of excess dead skin.

Some procedures can also encourage faster growth of new skin cells to speed up the regeneration process.

Aging slows down the skin regeneration process, but it doesnt ever stop it completely.

However, because the process becomes much slower as we age, the skin can appear thicker, less flexible, and more wrinkled or textured.

This is because the slower the regeneration, the more dead skin cells remain on the face.

Skin regeneration is a natural cycle that occurs as the skin cells turn over. In other words, dead skin cells on the top layer of the epidermis fall away, revealing fresh, newly created cells beneath.

By supporting this cycle with a healthy lifestyle and skin care routine, you can encourage a lustrous glow even as you get older.

Just remember: while boosting skin regeneration is possible, its natural for the cycle to slow down as you age. A few wrinkles and some texture are nothing to be ashamed of.

You can even think of them as signs of wisdom and experience.

Meg is a freelance journalist and features writer who covers culture, entertainment, lifestyle and health. Her writing has appeared in Cosmopolitan, Shondaland, Healthline, HelloGiggles, Readers Digest, Apartment Therapy, and more. T: @wordsbyMeg W: megwalters.co.uk

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Treat Yourself to a Spa Day With a $100 Deal on $600 Worth of Products From Elemis, U Beauty, Nest & More  E! NEWS

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7-year-old vows to find a cure for brother in need of bone marrow transplant  WJLA

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World's most radioactive man 'cried blood' as his skin melted in 83-day nightmare  Times Now

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How old are you, really? The answer is written on your face.  National Geographic UK

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Overview The three layers of skin on top of muscle tissue.What is the skin?

The skin is the bodys largest organ, made of water, protein, fats and minerals. Your skin protects your body from germs and regulates body temperature. Nerves in the skin help you feel sensations like hot and cold.

Your skin, along with your hair, nails, oil glands and sweat glands, is part of the integumentary (in-TEG-you-MEINT-a-ree) system. Integumentary means a bodys outer covering.

Three layers of tissue make up the skin:

Your epidermis is the top layer of the skin that you can see and touch. Keratin, a protein inside skin cells, makes up the skin cells and, along with other proteins, sticks together to form this layer. The epidermis:

The dermis makes up 90% of skins thickness. This middle layer of skin:

The bottom layer of skin, or hypodermis, is the fatty layer. The hypodermis:

One inch of your skin has approximately 19 million skin cells and 60,000 melanocytes (cells that make melanin or skin pigment). It also contains 1,000 nerve endings and 20 blood vessels.

As the bodys external protection system, your skin is at risk for various problems. These include:

You lose collagen and elastin as you age. This causes the skins middle layer (dermis) to get thinner. As a result, the skin may sag and develop wrinkles.

While you cant stop the aging process, these actions can help maintain healthier skin:

You should call your healthcare provider if you experience:

A note from Cleveland Clinic

As the bodys largest organ, your skin plays a vital role in protecting your body from germs and the elements. It keeps your body at a comfortable temperature, and nerves beneath the skin provide the sense of touch. This external body covering can have serious problems like skin cancer, as well as more common issues like acne and skin rashes. Your healthcare provider can offer tips to help keep skin healthy.

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Summary

human skin, in human anatomy, the covering, or integument, of the bodys surface that both provides protection and receives sensory stimuli from the external environment. The skin consists of three layers of tissue: the epidermis, an outermost layer that contains the primary protective structure, the stratum corneum; the dermis, a fibrous layer that supports and strengthens the epidermis; and the subcutis, a subcutaneous layer of fat beneath the dermis that supplies nutrients to the other two layers and that cushions and insulates the body.

The apparent lack of body hair immediately distinguishes human beings from all other large land mammals. Regardless of individual or racial differences, the human body seems to be more or less hairless, in the sense that the hair is so vestigial as to seem absent; yet in certain areas hair grows profusely. These relatively hairy places may be referred to as epigamic areas, and they are concerned with social and sexual communication, either visually or by scent from glands associated with the hair follicles.

The characteristic features of skin change from the time of birth to old age. In infants and children it is velvety, dry, soft, and largely free of wrinkles and blemishes. Children younger than two years sweat poorly and irregularly; their sebaceous glands function minimally. At adolescence hair becomes longer, thicker, and more pigmented, particularly in the scalp, axillae, pubic eminence, and the male face. General skin pigmentation increases, localized pigmented foci appear mysteriously, and acne lesions often develop. Hair growth, sweating, and sebaceous secretion begin to blossom. As a person ages, anatomical and physiological alterations, as well as exposure to sunlight and wind, leave skin, particularly that not protected by clothing, dry, wrinkled, and flaccid.

Human skin, more than that of any other mammal, exhibits striking topographic differences. An example is the dissimilarity between the palms and the backs of the hands and fingers. The skin of the eyebrows is thick, coarse, and hairy; that on the eyelids is thin, smooth, and covered with almost invisible hairs. The face is seldom visibly haired on the forehead and cheekbones. It is completely hairless in the vermilion border of the lips, yet coarsely hairy over the chin and jaws of males. The surfaces of the forehead, cheeks, and nose are normally oily, in contrast with the relatively greaseless lower surface of the chin and jaws. The skin of the chest, pubic region, scalp, axillae, abdomen, soles of the feet, and ends of the fingers varies as much structurally and functionally as it would if the skin in these different areas belonged to different animals.

The skin achieves strength and pliability by being composed of numbers of layers oriented so that each complements the others structurally and functionally. To allow communication with the environment, countless nervessome modified as specialized receptor end organs and others more or less structurelesscome as close as possible to the surface layer, and nearly every skin organ is enwrapped by skeins of fine sensory nerves.

The dermis makes up the bulk of the skin and provides physical protection. It is composed of an association of fibres, mainly collagen, with materials known as glycosaminoglycans, which are capable of holding a large amount of water, thus maintaining the turgidity of the skin. A network of extendable elastic fibres keeps the skin taut and restores it after it has been stretched.

The hair follicles and skin glands are derived from the epidermis but are deeply embedded in the dermis. The dermis is richly supplied with blood vessels, although none penetrates the living epidermis. The epidermis receives materials only by diffusion from below. The dermis also contains nerves and sense organs at various levels.

Human skin is enormously well supplied with blood vessels; it is pervaded with a tangled, though apparently orderly, mass of arteries, veins, and capillaries. Such a supply of blood, far in excess of the maximum biologic needs of the skin itself, is evidence that the skin is at the service of the blood vascular system, functioning as a cooling device. To aid in this function, sweat glands pour water upon its surface, the evaporation of which absorbs heat from the skin. If the environment is cold and body heat must be conserved, cutaneous blood vessels contract in quick, successive rhythms, allowing only a small amount of blood to flow through them. When the environment is warm, they contract at long intervals, providing a free flow of blood. During muscular exertion, when great quantities of generated heat must be dissipated, blood flow through the skin is maximal.

In addition to its control of body temperature, skin also plays a role in the regulation of blood pressure. Much of the flow of blood can be controlled by the opening and closing of certain sphincterlike vessels in the skin. These vessels allow the blood to circulate through the peripheral capillary beds or to bypass them by being shunted directly from small arteries to veins.

Human skin is permeated with an intricate mesh of lymph vessels. In the more superficial parts of the dermis, minute lymph vessels that appear to terminate in blind sacs function as affluents of a superficial lymphatic net that in turn opens into vessels that become progressively larger in the deeper portions of the dermis. The deeper, larger vessels are embedded in the loose connective tissue that surrounds the veins. The walls of lymph vessels are so flabby and collapsed that they often escape notice in specimens prepared for microscopic studies. Their abundance, however, has been demonstrated by injecting vital dyes inside the dermis and observing the clearance of the dye.

Because lymph vessels have minimal or no musculature in their walls, the circulation of lymph is sluggish and largely controlled by such extrinsic forces as pressure, skeletal muscle action, massaging, and heat. Any external pressure exerted, even from a fixed dressing, for example, interferes with its flow. Since skin plays a major role in immunologic responses of the body, its lymphatic drainage is as significant as its blood vascular system.

The intact surface of the skin is pitted by the orifices of sweat glands and hair folliclesthe so-called poresand is furrowed by intersecting lines that delineate characteristic patterns. All individuals have roughly similar markings on any one part of the body, but the details are unique. The lines are oriented in the general direction of elastic tension. Countless numbers of them, deep and shallow, together with the pores, give every region of the body a characteristic topography. Like the deeper furrows and ridges on the palms and soles, the skin lines are mostly established before birth. The fine details of each area of body surface are peculiar to each individual. Fingerprints are used as a means of personal identification because they have a high relief, more evident patternings, and can be easily obtained.

Some of the lines on the surface of the skin are acquired after birth as a result of use or damage. For example, furrows on the forehead are an accentuation of preexisting congenital lines that become strongly emphasized in old age. As the skin becomes less firm with aging, it also forms wrinkles. Certain occupations leave skin marks that, depending upon duration and severity, may be transient or permanent.

The palms of the hands and the soles of the feet are etched by distinct alternating ridges and grooves that together constitute dermatoglyphics. The ridges follow variable courses, but their arrangement in specific areas has a consistent structural plan. Though apparently continuous, the ridges have many interruptions and irregularities, branching and varying in length. Every small area of surface has ridge details not matched anywhere in the same individual or in any other individual, even in an identical twin. This infallible signature makes dermatoglyphics the best-known physical characteristic for personal identification.

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Skin disorders vary greatly in symptoms and severity. They can be temporary or permanent and may be painless or painful. Some skin conditions are minor, and others can be life threatening.

Some skin disorders have situational causes, while others may be genetic. While most skin disorders are minor, others can indicate a more serious issue.

Contact a doctor if you believe you may have one of these common skin problems.

There are many different types of skin disorders. Here are pictures of 25 different conditions, followed by a list of details for each.

Learn more about acne.

Learn more about cold sores and cold sores on dark skin.

Learn more about blisters.

Learn more about hives.

Learn more about actinic keratosis.

Learn more about rosacea.

Learn more about carbuncles.

This condition is considered a medical emergency. Urgent care may be required. Contact 911 or local emergency services.

Learn more about latex allergies.

Learn more about eczema.

Learn more about psoriasis.

Cellulitis is a medical emergency. A person should contact 911 or local emergency services if they have any symptoms of cellulitis.

Learn more about cellulitis.

Learn more about measles.

Learn more about basal cell carcinoma.

Learn more about squamous cell carcinoma.

Learn more about melanoma.

Learn more about lupus.

Learn more about contact dermatitis.

Learn more about vitiligo.

Learn more about warts.

Learn more about chickenpox.

Learn more about seborrheic eczema.

Learn more about keratosis pilaris.

Learn more about ringworm.

Learn more about melasma.

Learn more about impetigo.

Contact dermatitis is one of the most common occupational illnesses, often resulting from contact with chemicals or other irritating materials.

These substances can trigger a reaction that causes the skin to become itchy and inflamed. Affected areas might also appear red, purple, gray, or dark brown. Most cases of contact dermatitis arent severe, but they can be rather itchy.

Topical creams and avoiding the irritant are typical treatments.

Keratosis pilaris is a minor condition that causes small, rough bumps on the skin. These bumps usually form on the upper arms, thighs, or cheeks. Theyre typically red or white and dont hurt or itch.

Treatment isnt necessary, but medicated creams can improve skin appearance.

Some chronic skin conditions present from birth, while others appear suddenly later.

The cause of these disorders isnt always known. Many permanent skin disorders have effective treatments that enable extended periods of remission. However, theyre incurable, and symptoms can reappear at any time.

Examples of chronic skin conditions include:

Skin disorders are common in children. Children can experience many of the same skin conditions as adults. Infants and toddlers are also at risk of diaper-related skin problems.

Since children have more frequent exposure to other children and germs, they may also develop skin disorders that rarely occur in adults.

Many childhood skin problems disappear with age, but children can also inherit permanent skin disorders. In most cases, doctors can treat childhood skin disorders with topical creams, medicated lotions, or condition-specific drugs.

Common childhood skin disorders include:

Skin conditions have a wide range of symptoms. Symptoms on your skin that appear due to common problems arent always the result of a skin disorder. Such symptoms can include blisters from new shoes or chafing from tight pants.

However, skin problems with no obvious cause may indicate the presence of a skin disorder that requires treatment.

Skin irregularities that are typically symptoms of a skin disorder include:

Common known causes of skin disorders include:

Numerous health conditions and lifestyle factors can also lead to the development of certain skin disorders. Some skin conditions have no known cause.

Inflammatory bowel disease is a term for a group of intestinal disorders that cause prolonged inflammation of the digestive tract. These bowel-related disorders often cause skin problems.

The drugs used to treat these diseases can cause certain skin conditions, such as:

Many people with diabetes experience a skin problem due to their condition at some point.

Some of these skin disorders only affect people with diabetes. Others occur more frequently in people with diabetes because the disease increases the risk of infection and blood circulation problems.

Diabetes-related skin conditions include:

Lupus is a chronic inflammatory disease that can damage the skin, joints, or organs inside the body. Common skin problems that occur from lupus include:

Pregnancy causes significant changes in hormone levels that may lead to skin problems. Preexisting skin problems may change or get worse during pregnancy. Most skin conditions that arise during pregnancy go away after the baby is born. Others require medical attention during pregnancy.

Common skin conditions caused by pregnancy include:

Stress can cause hormonal imbalances, which may trigger or aggravate skin disorders. Stress-related skin problems include:

The sun can cause many different skin disorders. Some are common and harmless, while others are rare or life threatening. Knowing if the sun causes or worsens your skin disorder is important for treating it properly.

Sunlight exposure may cause or aggravate the following conditions:

Many skin disorders are treatable. Common treatment methods for skin conditions include:

Not all skin disorders respond to treatment, and some conditions go away without treatment.

People with permanent skin conditions often go through periods of severe symptoms. Sometimes people are able to force incurable conditions into remission. However, most skin conditions reappear due to certain triggers, such as stress or illness.

You can often treat skin disorders that are temporary and cosmetic with:

Certain skin disorders arent preventable, including genetic conditions and some skin problems due to other illnesses. However, its possible to prevent some skin disorders.

Follow these tips to prevent infectious skin disorders:

Noninfectious skin disorders, such as acne and atopic dermatitis, are sometimes preventable. Prevention techniques vary depending on the condition. Here are some tips for preventing some noninfectious skin disorders:

Learning about proper skin care and treatment for skin disorders can be very important for skin health. Some conditions require a doctors attention, while you can address others safely at home.

You should learn about your symptoms or condition and talk with a doctor to determine the best treatment methods.

According to the American Academy of Dermatology Association, acne is the most common skin condition in the United States. Other common skin disorders include atopic dermatitis, hair loss, and rosacea.

There are several serious skin conditions. In particular, melanoma is a type of skin cancer that can be especially dangerous, as it could spread to other parts of the body if not caught early. Cellulitis and latex allergy can also be very serious if left untreated.

A few examples of chronic skin conditions include rosacea, psoriasis, and vitiligo. While these conditions cant be cured, some may have treatments available to help manage symptoms.

Different types of conditions affect the skin. Some are chronic, while others are temporary. Some conditions may be painful or uncomfortable, but theyre not dangerous. Other conditions, such as skin cancer, can be life threatening.

The treatment for each depends on the specific cause. If you experience any new or unusual skin symptoms, its a good idea to have them evaluated by a doctor.

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Skin care: 5 tips for healthy skin

Good skin care including sun protection and gentle cleansing can keep your skin healthy and glowing.

Don't have time for intensive skin care? You can still pamper yourself by acing the basics. Good skin care and healthy lifestyle choices can help delay natural aging and prevent various skin problems. Get started with these five no-nonsense tips.

One of the most important ways to take care of your skin is to protect it from the sun. A lifetime of sun exposure can cause wrinkles, age spots and other skin problems as well as increase the risk of skin cancer.

For the most complete sun protection:

Smoking makes your skin look older and contributes to wrinkles. Smoking narrows the tiny blood vessels in the outermost layers of skin, which decreases blood flow and makes skin paler. This also depletes the skin of oxygen and nutrients that are important to skin health.

Smoking also damages collagen and elastin the fibers that give your skin strength and elasticity. In addition, the repetitive facial expressions you make when smoking such as pursing your lips when inhaling and squinting your eyes to keep out smoke can contribute to wrinkles.

In addition, smoking increases your risk of squamous cell skin cancer. If you smoke, the best way to protect your skin is to quit. Ask your doctor for tips or treatments to help you stop smoking.

Daily cleansing and shaving can take a toll on your skin. To keep it gentle:

A healthy diet can help you look and feel your best. Eat plenty of fruits, vegetables, whole grains and lean proteins. The association between diet and acne isn't clear but some research suggests that a diet rich in fish oil or fish oil supplements and low in unhealthy fats and processed or refined carbohydrates might promote younger looking skin. Drinking plenty of water helps keep your skin hydrated.

Uncontrolled stress can make your skin more sensitive and trigger acne breakouts and other skin problems. To encourage healthy skin and a healthy state of mind take steps to manage your stress. Get enough sleep, set reasonable limits, scale back your to-do list and make time to do the things you enjoy. The results might be more dramatic than you expect.

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Cynthias story

Cynthia had always been proud of her skin, especially her summer tan. But, as years went by, she saw her skin getting more fine lines and wrinkles. Cynthia began to worry about what other skin problems she might have. What were those brown spots on her hands and arms?

Your skin changes with age. It becomes thinner, loses fat, and no longer looks as plump and smooth as it once did. Your veins and bones can be seen more easily. Scratches, cuts, or bumps can take longer to heal. Years of suntanning or being out in the sunlight for a long time may lead to wrinkles, dryness, age spots, and even cancer. But there are things you can do to protect your skin and to make it feel and look better.

Many older people suffer from dry spots on their skin, often on their lower legs, elbows, and lower arms. Dry skin patches feel rough and scaly. There are many possible reasons for dry skin, such as:

Dry skin also can be caused by health problems, such as diabetes or kidney disease. Using too much soap, antiperspirant, or perfume and taking hot baths can make dry skin worse.

Some medicines can make skin itchy. Because older people have thinner skin, scratching can cause bleeding that may lead to infection. Talk to your doctor if your skin is very dry and itchy.

Here are some ways to help dry, itchy skin:

Older people may bruise more easily than younger people. It can take longer for these bruises to heal. Some medicines or illnesses may also cause bruising. Talk to your doctor if you see bruises and dont know how you got them, especially on parts of your body usually covered by clothing.

Over time, skin begins to wrinkle. Things in the environment, like ultraviolet (UV) light from the sun, can make the skin less elastic. Gravity can cause skin to sag and wrinkle. Certain habits, like smoking, also can wrinkle the skin.

A lot of claims are made about ways to make wrinkles go away. Most of them dont work. Some methods can be painful or even dangerous, and many must be done by a doctor. Talk with a doctor specially trained in skin problems, called a dermatologist, or your regular doctor if you are worried about wrinkles.

Age spots, once called liver spots, are flat, brown spots often caused by years in the sun. They are bigger than freckles and commonly show up on areas like the face, hands, arms, back, and feet. Using a broad-spectrum sunscreen that helps protect against two types of the suns rays (UVA and UVB) may prevent more age spots.

Skin tags are small, usually flesh-colored growths of skin that have a raised surface. They become common as people age, especially for women. They are most often found on the eyelids, neck, and body folds such as the armpit, chest, and groin.

Age spots and skin tags are harmless, although sometimes skin tags can become irritated. If your age spots or skin tags bother you, talk to your doctor about having them removed.

Skin cancer is a very common type of cancer in the United States. The main cause of skin cancer is the sun. Sunlamps and tanning booths can also cause skin cancer. Anyone, of any skin color, can get skin cancer. People with fair skin that freckles easily are at greatest risk. Skin cancer may be cured if it is found before it spreads to other parts of the body.

There are three types of skin cancers. Two types, basal cell carcinoma and squamous cell carcinoma, grow slowly and rarely spread to other parts of the body. These types of cancer are usually found on parts of the skin most often exposed to the sun, like the head, face, neck, hands, and arms. But they can happen anywhere on your body. The third and most dangerous type of skin cancer is melanoma. It is rarer than the other types, but it can spread to other organs and be deadly.

Check your skin once a month for things that may be signs of cancer. Skin cancer is rarely painful. Look for changes such as a new growth, a sore that doesnt heal, or a bleeding mole.

A = Asymmetry (one half of the growth looks different from the other half)

B = Borders that are irregular

C = Color changes or more than one color

D = Diameter greater than the size of a pencil eraser

E = Evolving; meaning the growth changes in size, shape, symptoms (itching, tenderness), surface (especially bleeding), or shades of color

See your doctor right away if you have any of these signs to make sure it is not skin cancer.

Some sun can be good for you, but to keep your skin healthy, be careful:

Your skin may change with age. But remember, there are things you can do to help. Check your skin often. If you find any changes that worry you, see your doctor.

Read about this topic in Spanish. Lea sobre este tema en espaol.

This content is provided by the NIH National Institute on Aging (NIA). NIA scientists and other experts review this content to ensure it is accurate and up to date.

Content reviewed: October 01, 2017

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Overview Wrinkles Open pop-up dialog box

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Wrinkles, especially around the eyes, mouth and neck, are common with aging as the skin in these areas gets thinner, drier and less elastic.

Wrinkles, a natural part of aging, are most prominent on sun-exposed skin, such as the face, neck, hands and forearms.

Although genetics mainly determine skin structure and texture, sun exposure is a major cause of wrinkles, especially for people with light skin. Pollutants and smoking also contribute to wrinkling.

If your wrinkles bother you, you have more options than ever to help smooth them or make them less visible. Medications, skin-resurfacing techniques, fillers and surgery top the list of effective wrinkle treatments.

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With repeated sun exposure, wrinkles can become very pronounced and deep, especially on the back of the neck.

Wrinkles are the lines and creases that form in your skin. Some wrinkles can become deep crevices or furrows and may be especially noticeable around your eyes, mouth and neck.

If you're concerned about the appearance of your skin, see a dermatologist. He or she can assess your skin and help you create a personalized skin care plan. A dermatologist can also recommend medical wrinkle treatments.

Wrinkles are caused by a combination of factors some you can control, others you can't:

Age. As you get older, your skin naturally becomes less elastic and more fragile. Decreased production of natural oils dries your skin and makes it appear more wrinkled.

Fat in the deeper layers of your skin diminishes. This causes loose, saggy skin and more-pronounced lines and crevices.

Exposure to ultraviolet (UV) light. Ultraviolet radiation, which speeds the natural aging process, is the primary cause of early wrinkling. Exposure to UV light breaks down your skin's connective tissue collagen and elastin fibers, which lie in the deeper layer of skin (dermis).

Without the supportive connective tissue, your skin loses strength and flexibility. Skin then begins to sag and wrinkle prematurely.

Here are some tips for protecting your skin and minimizing the appearance of wrinkles:

Protect your skin from the sun. Limit the time you spend in the sun, especially midday, and always wear protective clothing, such as wide-brimmed hats, long-sleeved shirts and sunglasses. Also, use sunscreen year-round when outdoors.

Choose a skin-care product with a built-in sun protection factor (SPF) of at least 15. The American Academy of Dermatology recommends using a broad-spectrum sunscreen with an SPF of 30 or more. Apply sunscreen generously, and reapply every two hours or more often if you're swimming or perspiring.

Wrinkles care at Mayo Clinic

Jan. 21, 2023

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Wrinkles - Symptoms and causes - Mayo Clinic

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Vivien Williams: Drink plenty of water. Don't smoke and wash your face and body each day with a gentle hypoallergenic soap for healthy-looking skin says Mayo Clinic dermatologist, Dr. Dawn Davis. And, after bathing,

Dawn Davis, M.D., Dermatology, Mayo Clinic: Moisturize with a hypoallergenic, fragrance-free moisturizer when you're done to help the skin hydrate.

Vivien Williams: With so many products from which to choose, how do you pick the right moisturizer? Dr. Davis says hypoallergenic is the key.

Dr. Davis: So you want it to be fragrance-free. Unscented doesn't necessarily mean that it doesn't have fragrance. Oftentimes unscented just means more chemicals.

Vivien Williams: What ingredient should you look for?

Dr. Davis: The most inert natural hypoallergenic product that you can find in a moisturizer is petrolatum.

Vivien Williams: As in petroleum jelly. Dr. Davis has another important tip for healthy skin care that could potentially save your life.

Dr. Davis: Please remember to wear your sunscreen.

Vivien Williams: For the Mayo Clinic News Network, I'm Vivien Williams.

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Dry skin - Symptoms and causes - Mayo Clinic

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Stem cells have been the object of much excitement and controversy amongst both scientists and the general population. Surprisingly, though, not everybody understands the basic properties of stem cells, let alone the fact that there is more than one type of cell that falls within the stem cell category. Here, Ill lay out the basic concepts of stem cell biology as a background for understanding the stem cell research field, where it is headed, and the enormous promise it offers for regenerative medicine.

Fertilization of an egg cell by a sperm cell results in the generation of a zygote, the single cell that, upon a myriad of divisions, gives rise to our whole body. Because of this amazing developmental potential, the zygote is said to be totipotent. Along the way, the zygote develops into the blastocyst, which implants into the mothers uterus. The blastocyst is a structure comprising about 300 cells that contains two main regions: the inner cell mass (ICM) and the trophoblast. The ICM is made of embryonic stem cells (ES cells), which are referred to as pluripotent. They are able to give rise to all the cells in an embryo proper, but not to extra-embryonic tissues, such as the placenta. The latter originate from the trophoblast [].

Even though it is hard to pinpoint exactly when or by whom what we now call stem cells were first discovered, the consensus is that the first scientists to rigorously define the key properties of a stem cell were Ernest McCulloch and James Till. In their pioneering work in mice in the 1960s, they discovered the blood-forming stem cell, the hematopoietic stem cell (HSC) [2, 3]. By definition, a stem cell must be capable of both self-renewal (undergoing cell division to make more stem cells) and differentiation into mature cell types. HSCs are said to be multipotent, as they can still give rise to multiple cell types, but only to other types of blood cells (see Figure 1, left column). They are one of many examples of adult stem cells, which are tissue-specific stem cells that are essential for organ maintenance and repair in the adult body. Muscle, for instance, also possesses a population of adult stem cells. Called satellite cells, these muscle cells are unipotent, as they can give rise to just one cell type, muscle cells.

Therefore, the foundations of stem cell research lie not with the famous (or infamous) human embryonic stem cells, but with HSCs, which have been used in human therapy (such as bone marrow transplants) for decades. Still, what ultimately fueled the enormous impact that the stem cell research field has today is undoubtedly the isolation and generation of pluripotent stem cells, which will be the main focus of the remainder of the text.

Figure 1: Varying degrees of stem cell potency. Left: The fertilized egg (totipotent) develops into a 300-cell structure, the blastocyst, which contains embryonic stem cells (ES cells) at the inner cell mass (ICM). ES cells are pluripotent and can thus give rise to all cell types in our body, including adult stem cells, which range from multipotent to unipotent. Right: An alternative route to obtain pluripotent stem cells is the generation of induced pluripotent stem cells (iPS cells) from patients. Cell types obtained by differentiation of either ES cell (Left) or iPS cells (Right) can then be studied in the dish or used for transplantation into patients. Figure drawn by Hannah Somhegyi.

Martin Evans (Nobel Prize, 2007) and Matt Kauffman were the first to identify, isolate and successfully culture ES cells using mouse blastocysts in 1981 []. This discovery opened the doors to the creation of murine genetic models, which are mice that have had one or several of their genes deleted or otherwise modified to study their function in disease []. This is possible because scientists can modify the genome of a mouse in its ES cells and then inject those modified cells into mouse blastocysts. This means that when the blastocyst develops into an adult mouse, every cell its body will have the modification of interest.

The desire to use stem cells unique properties in medicine was greatly intensified when James Thomson and collaborators first isolated ES cells from human blastocysts []. For the first time, scientists could, in theory, generate all the building blocks of our body in unlimited amounts. It was possible to have cell types for testing new therapeutics and perhaps even new transplantation methods that were previously not possible. Yet, destroying human embryos to isolate cells presented ethical and technical hurdles. How could one circumvent that procedure? Sir John Gurdon showed in the early 1960s that, contrary to the prevalent belief back then, cells are not locked in their differentiation state and can be reverted to a more primitive state with a higher developmental potential. He demonstrated this principle by injecting the nucleus of a differentiated frog cell into an egg cell from which the nucleus had been removed. (This is commonly known as reproductive cloning, which was used to generate Dolly the Sheep.) When allowed to develop, this egg gave rise to a fertile adult frog, proving that differentiated cells retain the information required to give rise to all cell types in the body. More than forty years later, Shinya Yamanaka and colleagues shocked the world when they were able to convert skin cells called fibroblasts into pluripotent stem cells by altering the expression of just four genes []. This represented the birth of induced pluripotent stem cells, or iPS cells (see Figure 1, right column). The enormous importance of these findings is hard to overstate, and is perhaps best illustrated by the fact that, merely six years later, Gurdon and Yamanaka shared the Nobel Prize in Physiology or Medicine 2012 [].

Since the generation of iPS cells was first reported, the stem cell eld has expanded at an unparalleled pace. Today, these cells are the hope of personalized medicine, as they allow one to capture the unique genome of each individual in a cell type that can be used to generate, in principle, all cell types in our body, as illustrated on the right panel of Figure 1. The replacement of diseased tissues or organs without facing the barrier of immune rejection due to donor incompatibility thus becomes approachable in this era of iPS cells and is the object of intense research [].

The first proof-of-principle study showing that iPS cells can potentially be used to correct genetic diseases was carried out in the laboratory of Rudolf Jaenisch. In brief, tail tip cells from mice with a mutation causing sickle cell anemia were harvested and reprogrammed into iPS cells. The mutation was then corrected in these iPS cells, which were then differentiated into blood progenitor cells and transplanted back into the original mice, curing them []. Even though iPS cells have been found not to completely match ES cells in some instances, detailed studies have failed to find consistent differences between iPS and ES cells []. This similarity, together with the constant improvements in the efficiency and robustness of generating iPS cells, provides bright prospects for the future of stem cell research and stem cell-based treatments for degenerative diseases unapproachable with more conventional methods.

Leonardo M. R. Ferreira is a graduate student in Harvard Universitys Department of Molecular and Cellular Biology

[] Stem Cell Basics: http://stemcells.nih.gov/info/basics/Pages/Default.aspx

[] Becker, A. J., McCulloch, E.A., Till, J.E. Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature 1963. 197: 452-4

[] Siminovitch, L., McCulloch, E.A., Till, J.E. The distribution of colony-forming cells among spleen colonies. J Cell Comp Physiol 1963, 62(3): 327-336

[] Evans, M. J. and Kaufman, M. Establishment in culture of pluripotential stem cells from mouse embryos. Nature 1981, 292: 151156

[] Simmons, D. The Use of Animal Models in Studying Genetic Disease: Transgenesis and Induced Mutation. Nature Education 2008,1(1):70

[] Thomson, J. A. et al. Embryonic stem cell lines derived from human blastocysts. Science 1998, 282(5391): 1145-1147

[] Takahashi, K. and Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006. 126(4): 663-76

[] The Nobel Prize in Physiology or Medicine 2012:

[] Ferreira, L.M.R. and Mostajo-Radji, M.A. How induced pluripotent stem cells are redefining personalized medicine. Gene 2013. 520(1): 1-6 [] Hanna J. et al. Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science 2007. 318: 1920-1923

[] Yee,J.Turning Somatic Cells into Pluripotent Stem Cells.Nature Education 2010.3(9):25

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Still Drinking Green Tea? Doctor Reveals A Healthier Drink With Proven Benefits For Diabetes, Aging, Oxidative Stress, And Cancer  Revyuh

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Still Drinking Green Tea? Doctor Reveals A Healthier Drink With Proven Benefits For Diabetes, Aging, Oxidative Stress, And Cancer - Revyuh

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RUDN Physician And Russian Scientists Investigate Long-term Effects Of Treating Diabetic Ulcers With Stem Cells  India Education Diary

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Burn wound healing involves a series of complex processes which are subject to intensive investigations to improve the outcomes, in particular, the healing time and the quality of the scar. Burn injuries, especially severe ones, are proving to have devastating effects on the affected patients. Stem cells have been recently applied in the field to promote superior healing of the wounds. Not only have stem cells been shown to promote better and faster healing of the burn wounds, but also they have decreased the inflammation levels with less scar progression and fibrosis. This review aims to highlight the beneficial therapeutic effect of stem cells in burn wound healing and to discuss the involved pathways and signaling molecules. The review covers various types of burn wound healing like skin and corneal burns, along with the alternative recent therapies being studied in the field of burn wound healing. The current reflection of the attitudes of people regarding the use of stem cells in burn wound healing is also stated.

The use of stem cell therapy is the yet to be discovered gold mine of science. A myriad of studies using stem cells are being done with promising results in various fields ranging from oncologic and hematologic diseases to organ transplants and wound healing. In the field of wound healing, the use of different types of stem cells has been reported for different types of wounds [13]. Burn wounds were of special interest due to the large number of cases of burns encountered nowadays, especially in the Middle Eastern Region and specifically in those areas with armed conflicts. Burn wounds have proven to be capable of having a devastating effect both functionally and cosmetically, necessitating the search for a better and more efficient cure. Being a very hot topic in the present field of research with constant studies and updates necessitated an updated review that encompasses the recent advances in stem cell therapy for burn wound healing in addition to relevant experimental studies. The literature was searched using the key words burn, stem cells, and wound healing. CINAHL, PubMed, EMBASE, and Medline were used as search engines to broaden the resources. The studies reported were not limited neither to humans nor by language and were mostly on animals unless otherwise specified. They are mostly reported in a chronological order of their publication dates, except when found relevant to group and mentioning some related studies consecutively.

Stem cells are undifferentiated pluripotential cells that are capable of producing other types of cells, including new stem cells identical to mother cells [4]. Stem cells can be of embryonal origin or adult origin, depending on the type of tissue they are derived from [4]. Embryonal stem cells are derived from either embryonal tissue or from germ cells in adults [4]. On the other hand, adult stem cells are derived from adult tissues of different organs, especially those with a high turnover rate such as intestines and bone marrow [4].

Stem cells have been implicated in the healing of wounds in general. However, the methods of application of the stem cells in burn wound healing are diverse, including topical application, local injection, intravenous or systemic injection, and dermal or carrier application. Several studies have shown the efficacy of stem cells in promoting faster and superior wound healing. Alexaki et al. [5] successfully used adipose derived mesenchymal stem cells in wound healing in mice and compared their effect with dermal fibroblasts. The application of stem cells in wounds promoted more efficient reepithelialization by their proliferative effect on keratinocytes [5]. Moreover, this effect of stem cells was found to be mediated by keratinocyte growth factor-1 (KGF-1) and platelet derived growth factor-BB (PDGF-BB) [5]. Amniotic fluid derived stem cells have also been used in wound healing. Skardal et al. [6] tested the effect of amniotic fluid derived stem cells in wound healing in a mouse model. Wound closure, reepithelialization, and angiogenesis were more rapid in mice treated with the stem cells in comparison to those treated with fibrin collagen gel only [6]. Additionally, stem cells did not integrate permanently in the tissue, thus, suggesting that their effect is due to released factors and not by direct interaction [6]. Additionally, bone marrow derived mesenchymal stem cells have also been used in wound healing. Leonardi et al. [7] utilized bone marrow derived stem cells in artificial dermal substitutes to promote wound healing. These stem cells were shown to increase vascular density in the wounds along with the rate of reepithelialization [7]. A study by Zhang et al. [8] examined the effect of activin signaling on the homing of stem cells to wound sites. It was also found that JNK and ERK signaling pathways were involved in activin signaling and eventually the homing of stem cells [8].

Concerning the physiology by which stem cells enhance the process of burn wound healing, several studies have been reported. Mansilla et al. [9] found evidence of cells in the bloodstream with identical phenotypes to mesenchymal bone marrow stem cells after acute large skin burns. Hence, it was concluded that these stem cells may have a role in promoting wound healing in burns. In a similar study, Fox et al. [10] reported increased levels of bone marrow derived endothelial progenitor cells in burn patients. These levels were proportional to the extent of the burn. The study also showed increased levels of angiogenic cytokines which may be involved in the signaling pathway for promoting the release of bone marrow derived stem cells. Focusing on the role of cytokines in burn wound healing, Payne et al. [11] studied the role of amnion derived cellular cytokine solution. In the study, Payne et al. used amnion derived multipotent progenitor cells to harvest cytokines and apply them in burn wound healing. Amnion derived cellular cytokine solution showed statistically significant improvement in the epithelialization of the burn wounds and the appearance of hair growth compared to controls [11]. In addition, the results demonstrated a faster epithelialization in burn wounds with increased frequency of application of the cytokines, further strengthening the role of stem cell derived cytokines in burn wound healing [11]. Furthermore, Foresta et al. [12] reported a positive linear correlation between endothelial progenitor cell blood levels and the total body surface area burnt. There was an increased level of endothelial progenitor cells in the bloodstream after escharectomy, posing a possible role of escharectomy in burn wound healing [12]. Additionally, stem cells could work by the release of bioactive peptides as proposed by Cabrera et al. [13] in their study where they showed that stem cells have an active role in burn wound healing by producing bioactive peptides, such as thymosin 4 and others.

More recent studies have also highlighted the role of stem cells in the process of wound healing in general and burn wound healing in specific. Koenen et al. [14] isolated acute wound fluids and chronic wound fluids and compared their effects on adipose tissue derived stem cell function in wounds. They came to the conclusion that acute wound fluids had a positive effect on the proliferation of adipose derived stem cells in wounds [14] while chronic wound fluids had a negative effect; the mentioned findings might explain the insufficient and slow healing process in chronic wounds due to a stem cell deficiency [14]. Furthermore, stem cells have been shown to decrease dermal fibrosis development in burn wound healing in mice [15]. Wu et al. performed a series of experiments which showed that bone marrow derived mesenchymal stem cells stimulate the formation of a basket weave organization of collagen in bleomycin treated skin, similar to normal skin [15]. Additionally, stem cell treatment of the skin decreased markers of myofibroblasts and downregulated type I collagen, leading to a decrease in the fibrosis that could have occurred to the skin [15]. Consequently, the role of stem cells in decreasing bleomycin induced fibrosis may be extrapolated to decrease fibrosis in burn wounds and improve their healing with less scar formation. Moreover, Lough et al. [16] performed a study in mice which showed a role for intestine derived human alpha defensin 5 in enhancing wound healing and decreasing its bacterial load. It induces leucine-rich repeat-containing G-protein-coupled receptors which are markers of adult epithelial stem cells both in skin and intestine [16]. Also implicated in the role of stem cells in burn wound healing is the role of SDF-1/CXCR4 signaling; Ding et al. [17] used interferon a2b in patients with burn wounds to suppress SDF-1/CXCR4 signaling. They found out that the decreased levels of signaling lead to better remodeling of hypertrophic scarring in the wounds [17]. Additional studies on the CXCR4 signaling pathway were done by Yang et al. [18] on irradiated mice. The mice having an overexpression of CXCR4, a receptor involved in the homing and migration of several stem cell types, showed an accelerated wound healing time [18]. Furthermore, Hu et al. [19] injected bone marrow derived mesenchymal stem cells into mice and studied the effect of blocking CXCR4 receptors. They found out that blocking the CXCL12/CXCR4 pathway, leading to activation of CXCR4, caused delayed wound closure in inflicted burn wounds. Moreover, CXCL12 levels were elevated in the burn wound one week after injury [19]. Hence, stem cells seem to be attracted to and attach to the burnt injury site by the CXCL12/CXCR4 pathway involving the CXCR4 receptors [18, 19]. The role of the ligand for the CXCR4 receptors, stromal cell derived factor-1 alpha (SDF-1a), has also been studied. L et al. [20] performed a study on the role of SDF-1a and its relation to the expression of miR-27b. It was found that SDF-1a expression was suppressed by direct binding of the miRNA to its 39UTR site [20]. As expected, miRNA expression was suppressed in wounds hence allowing better SDF-1a signaling and more homing of stem cells to the burn wounds [20]. In particular, miR-27b was found to be involved in the burn margins of wounds and in the mobilization of stem cells to the epidermis [20]. Chen et al. [21] performed experiments using porcine acellular dermal matrix on rats with inflicted 2nd degree burns. It stimulated collagen synthesis and stem cell proliferation and differentiation; porcine acellular matrix treated rats had a better and faster healing of the wounds.

Thus, in brief, the process of burn wound healing involves different types of growth factors, receptors, and cytokines. These factors are related to stem cell homing, differentiation, and proliferation. Additionally, when applied to burn wounds, they led to a better and faster healing process.

The use of stem cells for burn wound healing, as reported in the literature, dates back to 2003 with Shumakov et al. [22]. Shumakov et al. were the first to use mesenchymal bone marrow derived stem cells (BMSC) in burn wound healing and compared them to embryonic fibroblasts [22]. The experiments were done on rats where mesenchymal bone marrow derived stem cells were applied to wounds showing decreased cell infiltration of the wound and an accelerated formation of new vessels and granulation tissue in comparison with embryonic fibroblasts and controls (burn wounds with no transplanted cells) [22]. Hence, this study marked a new era in the research of burn wound healing by being the first to test the use of stem cells in this complex process. Following this, a study by Chunmeng et al. [23] found that systemic transplantation of dermis derived multipotent cells promoted the healing of wounds in irradiated rats compared to controls with no transplantation, noting that topical transplantation of the cells had no superior effect. In 2004, Rasulov et al. [24] were the first to report using bone marrow mesenchymal stem cells in humans; a female patient with extensive skin burns (IIIB 30% of body surface area) had the stem cells applied onto the burn surface. The application of stem cells caused faster wound healing and active neoangiogenesis [24]. Another study done by Rasulov et al. on rats also showed the superiority of stem cells in burn wound healing [25]. In the rat study, the application of mesenchymal stem cells on burns reduced cell infiltration, improved neoangeogenesis, and reduced the formation of granulation tissue [25]. The aforementioned conditions created a better medium for wound healing in burns. In a similar effort, Liu et al. [26] performed experiments on pigs where they applied collagen scaffolds with seeded mesenchymal stem cells onto the surface of inflicted burns; the latter were found to induce better burn wound healing with less contraction and better vascularization and keratinization. Moreover, in human cutaneous radiation wounds, Lataillade et al. [27, 28] reported two cases where stem cells where used to aid in burn wound healing. Mesenchymal stem cells were applied, in addition to surgical excision, flaps, and grafts, to burn wounds of cutaneous radiation patients. In these patients, the application of the mesenchymal stem cells decreased the levels of inflammation and promoted a better healing [27, 28]. Further on the role of stem cells in irradiated skin were the studies conducted by Dong et al. [29, 30], where they additionally inserted a vector of human beta defensin 2 into the stem cells. The mentioned studies showed a positive role for stem cells transfected with beta defensin 2 in burn wound healing by exhibiting antibacterial properties in infected burn wounds [29, 30]. In a similar experiment, Ha et al. [31] transfected mesenchymal stem cells with vectors of hepatocyte growth factor. The experiment, done on rats, compared the wound healing of a partial thickness burn treated with stem cells alone or stem cells transfected with hepatocyte growth factor [31]. The group treated with the transfected stem cells showed a significantly larger range of reepidermalization starting the first week, along with a thicker epidermis and lower content of collagen I at 3 weeks after burn [31]. In the same year (2010), Agay et al. [32] performed experimental studies by inflicting pigs with cutaneous radiation and studying the role of stem cells in the healing of the wounds. Intradermal mesenchymal stem cell injections were given locally in the affected area. They led to the accumulation of lymphocytes in the wound with better vascularization compared to controls (pigs with no injections of mesenchymal stem cells) [32]. Later on, Riccobono et al. [33] studied, in another experiment, the role of adipose tissue derived stem cells in the treatment of cutaneous radiation. Autologous, allogeneic, and acellular (empty, control) vehicles of adipose derived stem cells were grafted onto the burn wound areas [33]. Autologous but not allogeneic adipose derived stem cells were found to promote superior burn wound healing with no necrosis and decreased pain [33].

Aside to direct stem cell application to burn wounds, Kinoshita et al. [34] inflicted cutaneous radiation wounds to pigs and used expanders with and without basic fibroblast growth factor to determine their effect on burn wound healing. The group with basic fibroblast growth factor and expander showed greater proliferation of the dermis and epidermis along with increased neoangiogenesis [34]. Thus, basic fibroblast growth factor, which is known to promote the proliferation of mesenchymal stem cells, improved burn wound healing [34, 35].

In 2010, Yan et al. [36] studied the efficacy of porcine bone marrow derived mesenchymal stem cells combined with skin derived keratinocytes, both infected with recombinant retrovirus expressing human (h) platelet derived growth factor-A, in the healing of irradiated skin. The cells were loaded onto a cultured cutaneous substitute and compared their effect on healing with a cell-free cultured cutaneous substitute [36]. The substitute with cells stimulated faster healing, epithelialization, angiogenesis, and better granulation of the burn wound [36]. In another experiment, Collawn et al. [37] inflicted laser burn wounds to organotypic raft cultures. The burn wounds were treated with dermal grafts with and without adipose derived stromal cells [37]. The adipose derived stromal cell-containing grafts showed complete healing of the epidermis after two days, whereas the cell-free grafts still had areas of injury; hence, those stem cells had a role in promoting faster healing of the burnt areas [37]. More on cutaneous radiation treatment came from Xia et al. [38] who transfected human vascular endothelial growth factor 165 and human beta defensin 3 into bone marrow derived mesenchymal stem cells and used the cells to treat irradiated skin. The stem cell treated area, in comparison with cell-free controls, showed shorter healing times with better granulation and collagen deposition [38]. Additionally, Xue et al. [39] examined the effect of human mesenchymal stem cells in mouse models. Mice with inflicted burn wounds were injected locally, in the burn area, with the stem cells (controls injected cell-free injections) [39]. Wound healing was significantly faster when stem cells were included in the injection with an increased and denser neoangiogenesis [39]. Stem cell injections also had a role in resuming activity and regaining body weight more rapidly [39]. Similarly, Mansilla et al. [40] used mesenchymal stem cells in burn wound healing in pigs through an acellular dermal matrix embedded with anti-CD44 antibodies to promote homing and attachment of the stem cells [40]. This study concluded that the use of these dermal matrices with stem cells not only promoted better healing of the burn wound, but also stimulated the formation of hair follicles and regeneration of muscles and ribs [40].

Concerning stem cells from human umbilical cords, Liu et al. [41] studied the effect of human umbilical cord derived mesenchymal stem cells in the healing of severe burns inflicted in rats. The stem cells were intravenously injected into the affected rats [41]. Liu et al. found that the injection of the stem cells into the rats accelerated the wound healing compared to controls, decreased the count of inflammatory cells, downregulated interleukins 1 and 6, and increased the levels of interleukin 10 and TSG-6 [41]. Moreover, stem cell injected rats had increased neovascularization and VEGF levels [41]. Not only do stem cells promote faster wound healing in burns, but also they prevent the progression of burn injuries as showed by Singer et al. [42]. The latter performed an experiment while inflicting thermal burns to rats, with several rectangular burns on each rat separated by unburned interspaces [42]. Some of the rats received tail vein injections of mesenchymal stem cells, while others received saline injections [42]. After 7 days, all of the unburned spaces in the controls were necrotic [42]. However, 20% of the unburned spaces in rats with stem cells injections did not necrose [42]. Consequently, stem cells were also shown to play a possible role in the prevention of progression of burn injuries. Furthermore, in a study by Xu et al. [43], applying autologous bone marrow derived mesenchymal stem cells to grafted burn wounds, they demonstrated decreased contraction of the grafts.

In 2014, Yang et al. [44] attempted to integrate mesenchymal stem cells with fibrin glue into the dressing of burn wounds. They inflicted scald wounds on the back of rats and applied dressing with fibrin glue and stem cells in one group, fibrin glue only in the second, and no intervention in the third [44]. One month later, the treatment group with fibrin glue and stem cells showed significantly faster healing than the other two; moreover, this group had more proliferation of sebaceous glands and the appearance of hair follicle-like structures which were not present in the other groups [44]. In another experiment, Lough et al. [45] isolated leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6+) epithelial stem cells from the adnexal compartment of the skin of mice. They injected the harvested stem cells locally into inflicted burn wounds [45]. The wounds injected with stem cells showed a better healing along with increased vascular endothelial growth factor, platelet derived growth factor, and epidermal growth factor levels [45]. Stem cell injection also promoted the formation of nascent hair follicles and better neoangiogenesis in the wounds of the affected mice [45].

On the other hand, it is very pertinent to report another study in 2014 by Loder et al. [46] where they also tested the effect of adipose derived stem cells in the treatment of burns. The mice with inflicted burns that received stem cells injections showed no significant difference in comparison to controls (received saline injections) with respect to proliferation and vascularization [46]. Nevertheless, the role of stem cells in burn wound healing is a dynamic field and still under extensive research.

Another area of particular interest in the field of burn wound healing is the chemical burns of the cornea. In the year 2000, Dua and Azuara-Blanco [47] used autologous limbal stem cells for ocular surface reconstruction of the contralateral eye. It resulted in the formation of a better corneal surface with significant improvement in the vision and symptoms of the patients [47]. Several other experiments and trials using limbal stem cells showed similar results in inducing improvement of corneal healing and decreased neovascularization in both human (adults and children) and animal subjects [4853]. In 2007, Oh et al. [54] studied the therapeutic effects of mesenchymal stem cells on corneas with chemical burns. They reported that mesenchymal stem cell media and mesenchymal stem cell culture media (without the stem cells) reduced the inflammation and promoted neovascularization of the corneas [54]. They were also found to reduce the infiltration of CD4 cells, as well as IL-6, IL-10, and TGF-B1 levels. It is to be noted that the direct application of the stem cells provided superior results in the healing process in comparison with the stem cell culture media [54]. Another study by Ye et al. [55] utilized cyclophosphamide to suppress inflammatory reactions and the release of bone marrow stem cells into circulation. In this study, rabbits were inflicted with corneal alkali injuries. It was found that rabbits with an unsuppressed bone marrow had significantly greater reepithelialization of the corneas with clearer surfaces [55]. Thus, this study revealed the role of bone marrow cells in enhancing the healing of corneal chemical wounds. Furthermore, Sel et al. [56] inflicted alkali wounds on the corneal surfaces of mice and treated the corneas with bone marrow derived stem cells, CD117+ cells, or medium only as control. Reepithelialization of the wounds in the treatment groups was significantly faster than the control, with no difference in corneal transparency. Stem cells and CD117+ cells were absent from corneas after healing, thus suggesting that soluble factors may be responsible for the effect of the applied cells [56]. In a different study by Rama et al. [57], limbal stem cells were cultured on fibrin and used in corneal burns; not only did stem cells promote a better healing but also they had maintained a superior healing at a follow-up of 10 years later. Several other studies showed comparable results where mesenchymal derived or adipose derived stem cells promoted faster recovery of the corneal epithelium and decreased neovascularization, inflammation, and oxidative injury; moreover, stem cells stimulated the formation of clearer cornea media in some experiments [5861]. Additionally, Basu et al. [6264], in 2011 and 2012, reported a series of studies concerning the use of limbal stem cells in corneal burn wound healing. In the first study, Basu et al. [62] used limbal stem cells in corneal burn wound healing and followed them by penetrating keratoplasty procedures. Good results were observed but they were not compared to controls. However, in the second study, Basu et al. [63] observed that 66% of patients who failed primary procedures of corneal repair and who were subjected to a secondary limbal stem cell transplant on the affected cornea had successful improvement of the corneal surface with no neovascularization at a follow-up of two years. Later on, Sangwan et al. [64] used limbal biopsies from unaffected eyes and cultured them on amniotic membranes as substrates. Similar results to previous experiments were obtained with avascular epithelialization of the new corneal surfaces [64]. Furthermore and as demonstrated by Huang et al. [65], the use of allograft transplants of limbal stem cells in corneal burn wound healing also resulted in improved avascular corneal healing without the need for systemic immunosuppression. Pellegrini et al. [66] studied the biological factors that affected the stem cells role in corneal burn wound healing; the accurate number of stem cells used expressing high levels of the p63 transcription factor was shown to have important influence.

Stem cells do seem to have a very promising role in the treatment of burn wounds; however, other therapies are being developed to improve the treatment. For example, Klinger et al. [67] used fat injections in severe burn wounds as a trial to improve burn wound healing in humans. They did get results showing scar improvement and enhancement of tissue regeneration, but their study was limited to a small population [67]. In other studies, Auxenfans et al. [68] investigated the role of keratinocytes in improving wound healing in burns. They reported that keratinocytes induced a more rapid burn wound healing [68]. On the other hand, stromal vascular fraction has been also shown to play a possible role in enhancing burn wound healing [69]. Atalay et al. used isolated stromal vascular fraction in burn wound healing. It stimulated an increase in vascular endothelial growth factor and reduced the inflammation with an improved fibroblastic activity [69]. Additionally, Hussein et al. [70] studied the effect of Botox injections on burn wounds healing and found that Botox increased fibroblasts, TGF-B, and TNF-alpha levels and decreased inflammation, thus improving burn wound healing. Another recent study by Zhang et al. [71] showed a beneficial effect of heat shock protein 90 alpha on burn wound healing. It promoted faster healing and less inflammation. In addition, several other studies have examined the effects of different factors and substances such as curcumin, mast cell chymase, and phenytoin with hypericin on burn wound healing with promising results and better wound healing [7274].

Stem cells are commonly derived either from bone marrow, umbilical cord, adipose tissue, or skin. Natesan et al. [75] have even used debrided skin from severe burns as a source of stem cells for wound healing and regeneration. Hence, the adipose tissue that is discarded from burn wound debridement may now be of use for better wound healing. In addition, Natesan et al. [76], in another study, used isolated stem cells from debrided skin with fibrin and collagen based scaffolds. The dermal equivalents, created in the study, decreased wound contraction leading to a better matrix deposition and epithelialization [76]. Along the same line, van der Veen et al. [77] isolated mesenchymal stem cells from excised burn wound eschar. These stem cells showed similar abilities to adipose derived stem cells in differentiating into osteocytes, chondroblasts, and adipocytes [77].

A relatively recent approach by Li et al. [78] studied the role of electric fields in the migration of stem cells. They proved that epithelial stem cells migrate to the cathode in an induced electric field, knowing that endogenous electric fields exist naturally in wounds [78]. The migration of the stem cells was found to be proportional to the strength of the electric field and its duration, with the involvement of epidermal growth factor receptor and mitogen activated protein kinase-PI3K [78]. Hence, in addition to the use of stem cells in burn wounds, electric fields can be applied to the wounds to better direct their migration [78].

The role of stem cells in wound healing has been shown to be performed through several pathways, such as JNK and ERK59, and with the involvement of different factors and mediators, such as KGF-1 and PDGF-BB [5, 8]. Additionally, this role could also be carried out by the released factors and not only by direct integration of the stem cells into the wound scaffold or matrix [6].

Stem cells in burn wound healing have been found to follow the same mechanisms. The increased levels of stem cells in burn wounds suggested a possible enhancing role in aiding in the healing process [9, 10, 12, 13]. However, a lack of consistency of the outcome was documented. Different experiments may have used different amounts of purified stem cells, or stem cells at different stages of replication or differentiation in vitro, leading to what may seem different results. In brief, this review depicted the improved healing with stem cells qualitatively rather than quantitatively. To really demonstrate the value of different stem cells in the process of burn wound healing, more studies need to be done under optimal and well controlled conditions, aiming to measure a quantifiable improvement. Additionally, the excess use of stem cells may lead to unwanted results, such as increased fibrosis and thicker healed epithelium. Whether the effect is observed as a result of direct stem cell proliferation, or other induced substances and cells, needs to be studied in the future. Moreover, the role of cytokines released by stem cells along with bioactive peptides such as thymosin 4 has been documented to mediate the beneficial effect of the stem cell application in burn wound healing. Further data refer the superior healing probably not to the direct integration of the stem cells into the wound [11, 13]. Acute wound fluids were also shown to have a role in promoting faster healing of burn wounds, similarly reinforcing the role of mediators released by stem cells. Additionally, human alpha defensin 5 and the CXCL12/CXCR4 pathway with its signal SDF-1a were found to be inducers of stem cells in burn wounds [16, 18, 20].

In addition, stem cells have been shown to decrease cell infiltration, wound contraction, fibrosis, scar progression, and inflammation of burn wounds. Moreover, they have been found to promote faster burn wound healing and angiogenesis along with better granulation and the formation of hair follicles and sebaceous glands [15, 2245]. The studies reviewed showed positive results in both animal experiments and human trials, both in partial and full thickness injury burns. In addition, different ways of stem cell application have been used ranging from using stem cell scaffolds to systemic and intradermal injection [23, 25, 32]. Furthermore, the sources of stem cells used are multiple. They are derived from bone marrow, dermis, adipose tissue, and umbilical cords, among others [22, 23, 33, 41]. Stem cells have proved to be efficient not only in skin burns but also in corneal chemical burns, thus increasing the multiplicity of their use [5461].

Patients with burn wounds, especially those severely injured, tend to have lower quality of life [79]. The injury they suffer is not only physical but also psychological, affecting their jobs and relations with other people, especially their families [80, 81]. With the advance of burn wound treatment with time, patients self-esteem and quality of life have been improving [82, 83]. The hope is that the use of stem cells will open up a new arena of possibilities to improve the wound healing in burn patients, allowing patients to have faster healing, better scars, and a higher quality of life.

Stem cells have attracted many controversial public opinions over time. Many people argue that embryonic stem cell harvesting would be done by killing embryos which would be unethical [84]. Others would argue that even if embryos are used for stem cell research, it is not wrong. However, the path that this may lead to would be wrong such as embryo production for research purposes [84]. The public view towards the therapeutic use of stem cells has become more tolerant over time [85]. The role of educating people about the colossal potential for the use of stem cell has thus proven beneficial. People are now more educated about the different sources of stem cells and have become supportive of their use [85]. Regarding the acceptance of stem cells as an efficient therapy for burn wound healing in specific, a study done by Clover et al. [86] showed a very positive opinion. The biggest majority of people were willing to accept autologous stem cells, though a big percentage was also welcoming the idea of using allogeneic stem cells. These percentages did not differ between the use of stem cells for burn wounds or for the treatment of other diseases such as diabetes or Parkinsons [86].

In brief, the use of stem cells in burn wound healing appears to be very promising. While most studies were performed on animals, the application to humans is yet at its start. Hence, what is needed is more studies. Additionally, the signaling pathways followed by stem cells involved in the burn wound healing along with their factors and signals constitute a very dynamic and promising research field.

The authors declare that there is no conflict of interests regarding the publication of this paper.

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Adult stem cells maintain and repair tissues throughout the body

Embryonic stem cells are pluripotent cells derived from a 3 5 day old human embryo. They have the unique potential to develop into any of the other 200+ human cell types, and can significantly further our understanding of human development and diseases.

Embryonic stem cells also have important applications in drug development, and may one day be used to treat currently incurable conditions.

Stem cells are cells that have the potential to differentiate and give rise to other types of body cells. They are the basic materials from which all of the bodys specialized cells are made during whole-body development and, in adulthood, are used to maintain and repair body tissues. There are two types of human stem cells, and these are embryonic stem cells and adult stem cells.

Embryonic stem cells (ESCs) are stem cells derived from a 3 5 day old human embryo (AKA a blastocyst). ESCs are pluripotent, meaning they have the potential to become any of the other 200+ types of cells found in the human body. As the embryo develops, ESCs divide and differentiate to form the full complement of human body cells required for healthy function.

The first differentiation event in human embryos begins around 5 days after fertilization, so ESCs must be harvested before this time if they are to be used in medicine and research. At this early developmental stage, the cells of the embryo form an undifferentiated mass and have not yet taken on the characteristics or functions of specialized adult cells.

The ability of ESCs to develop into all other types of human cells makes them an invaluable research tool. Studies involving ESCs can advance our understanding of human development, disease treatment, and drug efficacy.

ESCs can be grown (or cultured) in a laboratory. When kept under the right conditions, stem cells will grow and divide indefinitely, without becoming differentiated. However, they will still maintain their ability to differentiate, making the ESC culture a convenient and renewable reservoir of human cells. When used in research, ECSs are converted into their desired cell types by manipulating the culture conditions.

Scientists can use stem cells to further their understanding of human development and diseases. By studying embryonic stem cells, researchers hope to learn how they differentiate to form tissues and organs, how diseases and conditions develop in these tissues, and how age affects their function.

Scientists can also use ESCs to test and develop new drugs and to help them identify new potential treatments for diseases like Parkinsons disease, heart failure, and spinal cord injuries.

ESCs have enormous potential in the development of restorative or regenerative medicine, in which damaged tissues are replaced by healthy ones. Currently, several stem cell therapies are possible and could be used to treat a variety of injuries and diseases. These include spinal cord injuries, retinal and macular degeneration, heart failure, type 1 diabetes, and tendon rupture.

However, research into the use of ESCs for regenerative medicine are ongoing, and better understanding is required before modern medicine can harness their full potential. In the future, scientists hope that stem cell therapies can be used to treat currently incurable or difficult to treat conditions, such as AIDS or certain types of cancer.

Currently, the most common stem cell therapy is multipotent hematopoietic stem cell (HSC) transplantation. This treatment involves the transplantation of hematopoietic (or blood) stem cells and is usually used to treat diseases affecting the blood cells, such as leukemia and anemia.

ESCs can also be used in the development of new drugs, which must be tested on living tissues to determine their efficacy and any possible side effects.

Stem cells cultured in the laboratory can be stimulated to differentiate into any type of human tissue, so they are commonly used in preclinical drug trials. Once the potential and risks of the new drug have been determined using stem cells, the treatment can be used in animal tests and, eventually, human clinical trials.

The discovery of ESCs has led to numerous breakthroughs in the field of medical research, and their potential as the basis for new therapies and drugs is enormous. However, there is ethical controversy surrounding the use of ESCs in research, primarily because harvesting these cells involves destroying a human embryo.

For those who believe that life begins at conception, this raises moral objections. Opponents of stem cell research believe that embryos have the same rights as any other human beings, and shouldnt be disposed of in the name of science.

Those who support the use of ESCs in medical research may argue that the embryos do not yet qualify as humans, as they are destroyed in the very early stages of development. ESCs are harvested at around day 5 of development when the embryo (or blastocyst) is nothing more than a mass of undifferentiated cells.

Embryos used as a source of ESCs are frequently obtained from IVF clinics, where they have been frozen following fertilization. Guidelines created by the National Institute of Health state that embryos can only be used for this purpose when they are no longer needed (meaning they will never be implanted in a womans uterus). Such embryos would eventually be discarded anyway, so it can be argued that they would be better used to advance medical research.

Adult stem cells (AKA somatic stem cells) are stem cells that are found in most adult tissues.

They can develop into other types of cells but, unlike, ESCs, they are not pluripotent (able to develop into any other type of cell). Adult stem cells are either multipotent (able to develop into a limited number of closely related cells) or unipotent (able to develop into just one type of cell).

Their main function is to maintain and repair the tissue in which they are found and to replace cells that die as a result of injury or disease.

Mesenchymal stem cells are found in many adult tissues, including the umbilical cord, bone marrow, and fat tissue. In the bone marrow, mesenchymal stem cells differentiate to form bone, cartilage, and fat cells.

Neural stem cells are found in the brain and develop into nerve cells and their supporting cells (glial cells).

Hematopoietic stem cells are found in the bone marrow and peripheral blood. They give rise to all kinds of blood cells, including red blood cells, white blood cells, and platelets.

Skin stem cells are found in the basal layer of the epidermis and form keratinocytes for the continuous regeneration of the epidermal layers.

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From pro soccer hopeful to hip hop artist with illness and addiction along the way, Tymaz Bagbani releases debut album  Toronto Star

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