Introduction

The skin is the largest organ in the body, coveringits entire external surface.The skinhas3 layersthe epidermis, dermis, and hypodermis,which have different anatomical structures and functions (seeImage.Cross Section, Layers of the Skin). The skin's structure comprises an intricate network that serves as the body's initial barrier against pathogens, ultraviolet (UV) light, chemicals, and mechanical injury.This organ also regulates temperature and the amount of water released into the environment.

Skin thicknessvariesby body region and isinfluenced by the thickness of the epidermal and dermal layers. Hairless skin in the palms of the hands and soles of the feet is the thickest due to the presence ofthe stratum lucidum, an extra layer in the epidermis.Regions lacking this extra layer are considered thin skin. Of these regions, the back has the thickest skin because it has a thick epidermis.[1][2][3]The skin's barrier function makes it susceptible to various inflammatory and infectious conditions. In addition, wound healing, sensory changes, and cosmesis are significant surgical concerns. Understanding the skin's anatomy and function is crucial for managing conditions across all medical fields.

Epidermis

The epidermis, the skin's outermost layer, is composed ofseveral strata and various cell types crucial for its function.

Layers of the epidermis:From the deepest to the most superficial, the epidermal layers are the stratum basale, stratum spinosum, stratum granulosum, stratum lucidum, and stratum corneum. The stratum basale,also known asstratum germinativum, is separated from the dermis by the basement membrane (basal lamina) and attached to it by hemidesmosomes. The cells in this layer are cuboidal to columnar, mitotically active stem cells that constantly produce keratinocytes. This layer also contains melanocytes. The stratum spinosum, comprising 8to 10 cell layers, isalsocalled the prickle cell layer. This layer contains irregular, polyhedral cells with cytoplasmic processes, sometimes called spines,that extend outward and contact neighboring cells by desmosomes. Dendritic cells can be found in this layer.[4][5]

The stratum granulosum has 3to 5 cell layers and containsdiamond-shaped cells with keratohyalin and lamellar granules. Keratohyalin granules contain keratin precursors that aggregate, cross-link, and form bundles. The lamellar granules contain the glycolipids secreted to the cell surfaces, functioning as anadhesiveto maintain cellular cohesion. The stratum lucidumcomprises 2 to 3 cell layers and ispresent in thicker skin on the palms and soles. This thin and clear layer consists of eleidin, a transformation product of keratohyalin. The stratum corneum has 20to 30 cell layers and occupies the uppermost epidermal layer. The stratum corneumis composed of keratin and dead keratinocytes (anucleate squamous cells) that form horny scales. This layer has the most variable thickness, especially in callused skin. Dead keratinocytesrelease defensins within this layer, which are part of our first line of immune defense mechanisms.[6][7]

Cells of the epidermis:The epidermal cells include keratinocytes, melanocytes, and Langerhans and Merkel cells(seeImage.Cells of the Epidermis). Keratinocytes are the predominant cells of the epidermis,originating from the basal layer. These cells produce keratin and lipids essentialforformingthe epidermal water barrier. Keratinocytes also contribute to calcium regulation by enablingUVB light absorption in the skin,which iscriticalfor vitamin D activation. Melanocytes derive from neural crest cells and primarilysynthesize melanin, the main skin pigment component. These cells are found between stratum basale cells. UVB light stimulates melanin secretion, protecting against further UV radiation exposure and acting as a built-in sunscreen. Melaninforms during the conversion of tyrosine to dihydroxyphenylalanine by the enzyme tyrosinase. Melanin then travels from cell to cell, relying on the long processesconnecting the melanocytes to the neighboring epidermal cells. Melanin granules from melanocytestransit through the lengthy processes to the cytoplasm of basal keratinocytes. This transfer occurs through cytocrine secretion, where keratinocytes phagocytose the tips of melanocyte processes.

Langerhanscellsare dendritic cells that act as the skin's first-line cellular immune defenders andare crucialfor antigen presentation. Special stains allow visualization of these cells in the stratum spinosum. Langerhans cells are of mesenchymal origin, derived from CD34-positive bone marrow stem cells, and are part of the mononuclear phagocytic system.These cells contain Birbeck granules and tennis racket-shaped cytoplasmic organelles. Langerhans cells express major histocompatibility complex (MHC) I and MHC II molecules, uptake antigens in the skin, and transport them to the lymph nodes. Merkel cells are oval-shaped modified epidermal cells found in the stratum basale, directly above the basement membrane. These cells serve as mechanoreceptors for light touch and are found in the palms, soles, and oral and genital mucosa, with the highest concentration in the fingertips. Merkel cells bind toadjoining keratinocytes through desmosomes and contain intermediate keratin filaments. The cell membranes of Merkel cells interact with free nerve endings in the skin.

Dermis

The dermis is connected to the epidermisby the basement membrane.The dermis consists of 2 connective tissue layers, papillary and reticular, which merge without clear demarcation. Thepapillary layeris the upper dermal layer,which isthinner and composed of loose connective tissue that contacts the epidermis. Thereticular layeris the deeper layer, which is thicker and less cellular. This layer consists of dense connective tissuecomposedof collagen fiber bundles. The dermis houses the sweat glands, hair, hair follicles, muscles, sensory neurons, and blood vessels.

Hypodermis

The hypodermis, also known as the subcutaneous fascia, is located beneath the dermis.This layer is the deepest skin layer and contains adipose lobules,sensory neurons, blood vessels, and scanty skin appendages, such as hair follicles.

Functions

The skin's comprehensive roles highlight its complexity and importance in maintaining overall health and well-being.These roles are discussed below.[8][9]

Barrier function:The skin has multiple protective roles, acting as a barrier against various external threats. The skinshieldsthe body fromexcessive water loss or absorption, invasion by microorganisms, mechanical and chemical trauma, and UV light damage. The cell envelope establishes the epidermal water barrier, a layer of insoluble proteins on the inner surface of the plasma membrane. This barrier is formed through thecross-linkingof small proline-rich proteins. Larger proteins such as cystatin, desmoplakin, and filaggrincontribute to the barrier's robust mechanics. The lipid envelope is a hydrophobic layer attached to the outer surface of the plasma membrane. Keratinocytes in the stratum spinosum produce keratohyalin granules and lamellar bodies containing a mixture of glycosphingolipids, phospholipids, and ceramides assembled within Golgi bodies. The contents of lamellar bodies are then secreted through exocytosis into the extracellular spaces between the stratum granulosum and corneum.

Immunological defense:The skin plays a crucial role in both adaptive and innate immunity. In adaptive immunity, antigen-presenting cells initiate T-cell responses, leading to increased levels of helper T cells, such as TH1, TH2, or TH17. In innate immunity, the skin produces various peptides with antibacterial and antifungal properties. The skin-associated lymphoid tissue is a significant component of the immune system,aiding in preventing infections, as even minor skin breaks can lead to infection. Langerhans cellsare part of the adaptive immune system, presenting foreign antigens encountered in the skin to T cells.

Regulation of homeostasis:The skin plays a vital role in maintaining body temperature and water balance. This organregulates heat exchange with the environment, particularly through the blood vessels and sweat glands. The skin managesthe rate and amount of water evaporation and absorption.

Endocrine and exocrine functions:Keratinocytes produce vitamin D by converting 7-dehydrocholesterol under UV light exposure. These cells also express the vitamin D receptor and contain enzymes that activate vitamin D, essential for the proliferation and differentiation of keratinocytes. The skin's exocrine functions include temperature control by perspiration and skin protection by sebum production. Sweat and sebaceous glands are crucial to these functions.

Sensory functions:The skin is equipped with nociceptors that allow for the sensation of touch, heat, cold, and pain, facilitating interaction with the environment. The skin's sensory roles are essential for an individual's movement, protection, andinteraction with the environment.

Diagnostic indicator:Skin characteristics such aspigmentation, smoothness, elasticity, and turgor provide insights into an individual's overall health status. Skin assessment is often a crucialpartof a person's physical examination.[10][11]

Cell division, desquamation, and sheddingin the skin:Cell division occurs in the stratum basale. Basal cells (young keratinocytes)begin the synthesis of keratinous tonofilaments, whichare grouped into bundles called tonofibrils. Older keratinocytes are then pushed into the stratum spinosum after mitosis.Skincellsbegin toproduce keratohyalin granules with intermediate-associated proteins, filaggrin, and trichohyalin in the upper part of the spinous layer. Thisprocess helps aggregate keratin filaments and convert granular cells into cornified cells, known as keratinization. Cells also produce lamellar bodies during this stage.

Keratinocytescontinue to move into the stratum granulosum afterward, where they become flattened and diamond-shaped. The cells accumulate keratohyalin granules mixed between tonofibrils.Keratinocytesthen continue to the stratum corneum, flattening and losing organelles and nuclei. The keratohyalin granules turn tonofibrils into a homogenous keratin matrix.Cornified cells reach the surface and are desquamated when desmosomes disintegrate. The proteinase activity of kallikrein-related serine peptidase is triggered by lowered pH near the surface. The processes ofskinshedding and desquamation vary slightly by body region.Hairless skincomprisesmore layers, withtheadditionof thestratum lucidum. Thus, keratinocytes in body regions with hairless skin go through more layers before reaching the surface.[12][13]

The epidermisis derived from ectodermal tissue. The dermis and hypodermisare derived from mesodermal tissue from somites. The mesoderm is also responsible for the formation of Langerhans cells. Neural crest cells, responsible for specialized sensory nerve endings and melanocyte formation, migrate into the epidermis during epidermal development.[14][15]

Blood vessels and lymphatic vessels are found in the skin's dermal layer.Blood supply to the skin comprises 2 plexusesonebetween the papillary and reticular dermal layers and another between the dermis and subcutaneous tissues.Blood supply to the epidermis is through the superficial arteriovenous plexus (subepidermal/papillary plexus). These vessels are important for temperature regulation. The body regulates temperature by increasing blood flowto the skin, transferring heatfrom the bodyto the environment.The autonomic nervous system controls the changes in blood flow.Sympathetic stimulation results in vasoconstriction, resulting in heat retention.Conversely, vasodilationleads to heat loss. Vasodilation is the body's response to increased body temperature,resulting from inhibiting the sympathetic centers in the posterior hypothalamus. In contrast, decreased body temperature causes vasoconstriction.[16][17]

Nerves of the skin include both somatic and autonomic nerves. The somatic sensory systemtransmitspain (nociception), temperature, light touch, discriminative touch, vibration, pressure, and proprioception sensations to the central nervous system. Specialized cutaneous receptors and end organs mediate perception, including Merkel disks and Pacinian, Meissner, and Ruffini corpuscles. Autonomic innervation controls vasculature tone, hair root pilomotor stimulation, and sweating. The free nerve endings extend into the epidermis and are responsible for sensing pain, heat, and cold. These sensory structures are most numerous in the stratum granulosum layer andaround most hair follicles. Merkel disks sense light touch andreaches the stratum basale layer. The other nerve endings are found in the deeper portions of the skin and include the Pacinian, Meissner, and Ruffini corpuscles. The Paciniancorpusclessense deep pressure. The Meissner corpuscles sense low-frequency stimulation at the level of the dermal papillae.TheRuffini corpuscles sense pressure.[18][19][20]

The arrector pili muscles are bundles of smooth muscle fibers attached to the connective tissue sheath of hair follicles. Contraction of these muscles pulls the hair follicle outward, erecting the hair. The arrector pili also compress the sebaceous glands, facilitating sebum secretion. Hair does not exit perpendicularly but at an angle. The erection of hair, known as piloerection, produces goosebumps, giving the skin a bumpy appearance when exposed to cold temperatures.[21]Studies show that piloerection contributes to thermoregulation and stem cell growth.[22]

Langer lines, also known as cleavage lines, are topological lines used to defineskin tension.Theselines correspond to the alignment of collagen and elastic fibers in the reticular dermis. Less scarring occurs ifsurgical incisions are made along these lines.[23]

The skin's clinical significance spans all medical disciplines. A few are discussed below.

Dermatomes

Dermatomes areskin segments divided based on afferent nerve distribution, numbered according to spinal vertebral levels. Spinal nerves comprise8 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 1 coccygealnerve. Diseasessuch as shingles caused by varicella-zoster infection manifest pain and rashes in dermatomal patterns. Dermatomes also aid inlocalizing spinal injuries.

Squamous Cell Carcinoma

Squamous cell carcinoma is amalignancy arising from mutated keratinocytes,typically due to UV damage in individuals with type I or II skin types. These individuals typically have light skin, blue or green eyes, and red or blonde hair and burn without tanning.The lesions oftenappearasscaly, flaky, thick red patches that may bleed.Somesquamous cell carcinoma tumors resemble warts.This type of skin cancer can metastasize. Squamous cell carcinoma often arises from actinic keratosespremalignant lesions with cutaneous hornsdeveloping fromchronicUV damage.[24]

Basal Cell Carcinoma

Basal cell carcinoma is a malignant neoplasm of the basal layers of the epidermis. Unlikesquamous cell carcinoma, itis much less likely to metastasize.This type of skin cancer is more common in sun-exposed areas, often appearing as pearly papules on the face, with telangiectasias and a great tendency to ulcerate.

Melanoma

Melanoma is a highly invasive malignant melanocyte tumor that is fatal but rarer than skinsquamous cell carcinoma and basal cell carcinoma. This neoplasm's high metastatic potential is significantly mediated bylesiondepth.Melanoma can be found anywhere on the body and is typically irregularly pigmented but can be amelanotic.[25]

Langerhans Cell Histiocytosis

Langerhans cell histiocytosis is a type of cancer in which Langerhans cells accumulate in the body andformgranulomas, often in the bones, causing bone pain.These granulomas can also appear in the skin, producing rashes, erythematous papules, or blisters (seeImage.Histology, Trichodysplasia Spinulosa). Notably, Langerhans cellhistiocytosis can affect the pituitary gland, leading to diabetes insipidus, infertility, or other endocrine disorders due to hormone deficiencies. Pancytopenia is apotentially fatal Langerhans cellhistiocytosis complication, manifesting with anemia, thrombocytopenia, and leukocytopenia, caused by overcrowding of Langerhans cells in the bone marrow.[26]

Merkel Cell Carcinoma

Merkel cell carcinoma is an uncommon cancer of the Merkel cells. This tumor is categorized as a neuroendocrine small cell carcinoma. Clinically,Merkelcell carcinoma often presents as a painless, solitary cutaneous or subcutaneous nodule, sometimes with a cystic appearance. The nodule can be red, pink, violet, blue, or skin-colored. Lesions may ulcerate or have satellite lesions.Merkel cell carcinoma is typically smaller than 20 mm at diagnosis but shows rapid tumor growth over a few months.[27]

Pemphigus Vulgaris

Pemphigus vulgaris is an autoimmune disease that targets the desmosomes, the intercellular proteins connecting keratinocytes. Desmosome degradation results in acantholysis and the formation ofeasily ruptured blisters within the epidermis. The disease is characterized by a positive Nikolsky sign, where the epidermis peels away upon rubbing.

Bullous Pemphigoid

Bullous pemphigoid is a blistering disease that affects older adults, causing tense subepidermal blisters.The conditionis causedby antibodies targeting hemidesmosomes, which connect the epidermis to the dermis at the basement membrane. This condition is not acantholytic and does not show a positive Nikolsky sign.[28]

ScaldedSkinSyndrome

Scalded skin syndromearises fromthe effects of the exfoliative toxin released byStaphylococcal aureus. The condition manifests as generalized skin exfoliationwith apositiveNikolsky sign, a severely burned (intensely red) appearance, and fever.[29][30]

Drug Reactions

Various drug reactions manifest in the skin, including erythema multiforme and the syndromes of drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson, and toxic epidermal necrolysis. These conditions are often associated with certain medications, including sulfa-containing drugs,nonsteroidal anti-inflammatory drugs, and antiepileptics.[31][32]

The epidermis contains much of our normal flora,with the microbiome varying by body region. The microorganisms inhabiting our skin surfaces are nonpathogenic and can be commensal or mutualistic. The bacteria that tend to predominate are Staphylococcusepidermidis andS aureus, Cutibacterium acnes, Corynebacterium, Streptococcus, Candida, and Clostridium perfringens. However, infections may occur when the protective skin barrier is altered or breached.[33]

Histology, Trichodysplasia Spinulosa. The left column shows hematoxylin and eosin staining of healthy skin (A1) and trichodysplasia spinulosa lesional skin (B1) at low power. At high power, healthy (A2) and trichodysplasia spinulosa (B2) epidermis and (more...)

Cross Section, Layers of the Skin. This is a cross-section view of the hair follicles, hair roots and shafts, sweat glands, pores, epidermis, dermis, and hypodermis. The papillary and reticular layers are also included. The eccrine sweat gland is located (more...)

Cells of the Epidermis. The image shows stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum, stratum basale, and dermis. Contributed by C Rowe

Disclosure: Hani Yousef declares no relevant financial relationships with ineligible companies.

Disclosure: Mandy Alhajj declares no relevant financial relationships with ineligible companies.

Disclosure: Adegbenro Fakoya declares no relevant financial relationships with ineligible companies.

Disclosure: Sandeep Sharma declares no relevant financial relationships with ineligible companies.

Original post:
Anatomy, Skin (Integument), Epidermis - StatPearls - NCBI Bookshelf

Skin Stem Cells Comments Off on Anatomy, Skin (Integument), Epidermis – StatPearls – NCBI Bookshelf | June 16th, 2025

The weather is getting cooler and many of us are turning to hot showers and baths to warm up and wind down.

But what actually happens to your skin when you have really hot showers or baths?

Your skin is your largest organ, and has two distinct parts: the epidermis on the outside, and the dermis on the inside.

The epidermis is made up of billions of cells that lay in four layers in thin skin (such as on your eyelids) and five layers in thick skin (such as the on sole of your foot).

The cells (keratinocytes) in the deeper layers are held together by tight junctions. These cellular bridges make waterproof joins between neighbouring cells.

The cells on the outside of the epidermis have lost these cellular bridges and slough off at a rate of about 1,000 cells per one centimetre squared of skin per hour. For an average adult, thats 17 million cells per hour, every day.

Under the epidermis is the dermis, where we have blood vessels, nerves, hair follicles, pain receptors, pressure receptors and sweat glands.

Together, the epidermis and dermis (the skin):

So, your skin is important and worth looking after.

Washing daily can help prevent disease, and really hot baths often feel lovely and can help you relax. That said, there are some potential downsides.

Normally we have lots of healthy organisms called Staphyloccocus epidermis on the skin. These help increase the integrity of our skin layers (they make the bonds between cells stronger) and stimulate production of anti-microbial proteins.

These little critters like an acidic environment, such as the skins normal pH of between 4-6.

If the skin pH increases to around 7 (neutral), Staphyloccocus epidermis nasty cousin Staphyloccocus aureus also known as golden staph will try to take over and cause infections.

Having a hot shower or bath can increase your skins pH, which may ultimately benefit golden staph.

Being immersed in really hot water also pulls a lot of moisture from your dermis, and makes you lose water via sweat.

This makes your skin drier, and causes your kidneys to excrete more water, making more urine.

Staying in a hot bath for a long time can reduce your blood pressure, but increase your heart rate. People with low blood pressure or heart problems should speak to their doctor before having a long hot shower or bath.

Heat from the shower or bath can activate the release of cytokines (inflammatory molecules), histamines (which are involved in allergic reactions), and increase the number of sensory nerves. All of this can lead to itchiness after a very hot shower or bath.

Some people can get hives (itchy raised bumps that look red on lighter skin and brown or purple on darker skin) after hot showers or baths, which is a form of chronic inducible urticaria. Its fairly rare and is usually managed with antihistamines.

People with sensitive skin or chronic skin conditions such as urticaria, dermatitis, eczema, rosacea, psoriasis or acne should avoid really hot showers or baths. They dry out the skin and leave these people more prone to flare ups.

The skin on your hands or feet is least sensitive to hot and cold, so always use your wrist, not your hands, to test water temperature if youre bathing a child, older person, or a disabled person.

The skin on your buttocks is the most sensitive to hot and cold. This is why sometimes you think the bath is OK when you first step in, but once you sit down it burns your bum.

You might have heard women like hotter water temperature than men but thats not really supported by the research evidence. However, across your own body you have highly variable areas of thermal sensitivity, and everyone is highly variable, regardless of sex.

Moisturising after a hot bath or shower can help, but check if your moisturiser is up to the task.

To improve the skin barrier, your moisturiser needs to contain a mix of:

Not all moisturisers are actually good at reducing the moisture loss from your skin. You still might experience dryness and itchiness as your skin recovers if youve been having a lot of really hot showers and baths.

If youre itching after a hot shower or bath, try taking cooler, shorter showers and avoid reusing sponges, loofahs, or washcloths (which may harbour bacteria).

You can also try patting your skin dry, instead of rubbing it with a towel. Applying a hypoallergenic moisturising cream, like sorbolene, to damp skin can also help.

If your symptoms dont improve, see your doctor.

See the original post here:
What actually happens to my skin when I have a really, really hot ...

Skin Stem Cells Comments Off on What actually happens to my skin when I have a really, really hot … | June 16th, 2025

Drug targeting on skin cancer stem cell niche. The figure depicts the...  ResearchGate

Read more from the original source:
Drug targeting on skin cancer stem cell niche. The figure depicts the... - ResearchGate

Skin Stem Cells Comments Off on Drug targeting on skin cancer stem cell niche. The figure depicts the… – ResearchGate | May 26th, 2025

Want to look young and be healthy? Try these five Harvard nutritionist-approved foods to boost stem cells for organ and skin repair  Times of India

The rest is here:
Want to look young and be healthy? Try these five Harvard nutritionist-approved foods to boost stem cells for organ and skin repair - Times of India

Skin Stem Cells Comments Off on Want to look young and be healthy? Try these five Harvard nutritionist-approved foods to boost stem cells for organ and skin repair – Times of India | May 26th, 2025

Exosomes: What Are They, Does your Skin Care Need Them and More  NBC News

Read more:
Exosomes: What Are They, Does your Skin Care Need Them and More - NBC News

Skin Stem Cells Comments Off on Exosomes: What Are They, Does your Skin Care Need Them and More – NBC News | May 18th, 2025

I Went to South Korea for a Week of Cutting-Edge Skin Treatments  Allure

Follow this link:
I Went to South Korea for a Week of Cutting-Edge Skin Treatments - Allure

Skin Stem Cells Comments Off on I Went to South Korea for a Week of Cutting-Edge Skin Treatments – Allure | May 6th, 2025

Comprehensive Analysis of Stem Cell Therapy on Skin Wound Healing: a systematic review and meta-analysis  Frontiers

See original here:
Comprehensive Analysis of Stem Cell Therapy on Skin Wound Healing: a systematic review and meta-analysis - Frontiers

Skin Stem Cells Comments Off on Comprehensive Analysis of Stem Cell Therapy on Skin Wound Healing: a systematic review and meta-analysis – Frontiers | May 6th, 2025

5 Best Stem Cell Companies to Invest In (May 2025)  Securities.io

Read the original post:
5 Best Stem Cell Companies to Invest In (May 2025) - Securities.io

Skin Stem Cells Comments Off on 5 Best Stem Cell Companies to Invest In (May 2025) – Securities.io | May 6th, 2025

Tracking Tissue Development to Inspire Regenerative Therapies  the-scientist.com

Continued here:
Tracking Tissue Development to Inspire Regenerative Therapies - the-scientist.com

Skin Stem Cells Comments Off on Tracking Tissue Development to Inspire Regenerative Therapies – the-scientist.com | April 14th, 2025

Mesenchymal stem cells and their ex osomes: a novel approach to skin  ResearchGate

The rest is here:
Mesenchymal stem cells and their ex osomes: a novel approach to skin - ResearchGate

Skin Stem Cells Comments Off on Mesenchymal stem cells and their ex osomes: a novel approach to skin – ResearchGate | April 14th, 2025

Dame Sandra Biskind And Stem Cell Rejuvenation  Anti Aging News

Follow this link:
Dame Sandra Biskind And Stem Cell Rejuvenation - Anti Aging News

Skin Stem Cells Comments Off on Dame Sandra Biskind And Stem Cell Rejuvenation – Anti Aging News | March 22nd, 2025

Skin cells can now be directly converted into neurons  Earth.com

Read the original here:
Skin cells can now be directly converted into neurons - Earth.com

Skin Stem Cells Comments Off on Skin cells can now be directly converted into neurons – Earth.com | March 22nd, 2025

Whether through injury or simple wear and tear, the skins integrity and function can be easily compromised. Although this impacts billions of people worldwide, little is known about how to prevent skin degeneration.

The Harvard Stem Cell Institute (HSCI) Skin Program is committed to understanding why skin sometimes fails to heal or forms scars, as well as why skin inevitably becomes thin, fragile, and wrinkled with age. The Skin Programs ultimate goal is to identify new therapies for skin regeneration and rejuvenation.

Wound healing is a major problem for many older individuals. Furthermore, chronic, non-healing skin ulcers are a major source of health care costs and patient morbidity and mortality.

Human skin repairs itself slowly, via the formation of contractile scars which may cause dysfunction. In contrast, the axolotl salamander can readily regrow a severed limb, the spiny mouse has densely haired skin that heals with remarkable speed, and the skin of the growing human embryo can regenerate after trauma without the need for any scar formation. By studying these examples, scientists are finding clues for how to enhance skin healing through a more regenerative response.

During normal wound healing, scars form from dermal cells that align in parallel. But when this alignment is disrupted by a biodegradable scaffold that directs cells to grow in a random orientation, the cells follow the diverse differentiation program necessary for true regeneration.

HSCI scientists have also identified biomarkers for the key cells involved in skin regeneration, and are developing therapeutic strategies for their enrichment and activation. Ongoing clinical trials are using skin stem cells to treat chronic, non-healing ulcers, and early results are promising.

Additional approaches include 3D bioprinting, where skin stem cells are layered into a complex structure that mimics skin and could be potentially used for transplantation.

Skin aging can be thought of as a form of wounding, in which stem cells no longer maintain normal skin thickness, strength, function, and hair density. Understanding how to harness stem cells for scarless wound healing will also provide key insights into regenerating aged skin, a process termed rejuvenation. Multidisciplinary collaborators in the HSCI Skin Program are investigating the biological basis for how the skin ages over time and when exposed to ultraviolet radiation.

In addition to aging, skin stem cells also may mistake normal regions of the skin as wounds, then erroneously attempt to fill them. HSCI investigators are exploring whether this may be one of the underpinnings of psoriasis, a common and devastating disorder.

These areas of investigation are just the beginning. Skin stem cell biology has the potential to provide key insights into the mechanisms of regeneration for other organs in the body.

See the rest here:
Skin Regeneration and Rejuvenation | Harvard Stem Cell Institute (HSCI)

Skin Stem Cells Comments Off on Skin Regeneration and Rejuvenation | Harvard Stem Cell Institute (HSCI) | March 1st, 2025

1. Introduction

Stem cells are unspecialized cells and are the essential building blocks of all organisms. They can differentiate into any specialized cell within an organism [1]. In this capacity, stem cells possess the ability to self-renewal, in addition to differentiating into all cells within tissues and ultimately organ systems [2, 3, 4]. Stem cells exist from conception and remain functional through adulthood, with many regulatory factors responsible for their specialization. As stem cells mature, differentiation becomes more limited which is referred to as commitment to a specific lineage. This means a unipotent stem cell is restricted in differentiation compared to a pluripotential stem cell (PSC) that can produce a variety of lineage specific cells. Thus, PSCs are more restricted when compared to a totipotent stem cell (TSC) [5, 6].

TSCs are capable of cell division with the ability to differentiate into mature cells comprising all the physiological systems associated with an intact and complete organism [6]. TSCs have unlimited potential to fully differentiate. This property allows TSCs to form both embryonic and extra-embryonic structures such as the placenta and the tissues associated with pregnancy [7, 8]. An example of a TSC is the zygote that forms after a sperm fertilizes an egg. TSCs will form a blastocyst which develops the inner cell mass (ICM). The ICM contains a unique population of stem cells known as embryonic stem cells (ESCs). ESCs are capable of remaining pluripotent in vitro [9, 10]. ESCs form the three germ layers associated with developmental biology, i.e., ectoderm, mesoderm, and endoderm [10], thus providing the core foundation of an organism through each germ layer by providing all the anatomical and physiological systems of the organism [11].

Pluripotential stem cells (PSCs) form structures associated with only the germ layers [11]. Another example of stem cells possessing pluripotency was achieved following the reprogramming capability to produce induced pluripotent stem cells (iPSCs) [12]. iPSC pluripotency is a continuum, starting from totipotent cells to cells possessing less potency as in multi-, oligo- or unipotent cells. The independence of iPSCs allows for using improved methods that are more promising for therapeutic stem cell use now and for future applications as defined in regenerative medicine [13].

Within their respective lineages, multipotent stem cells can generate more specialized cells. It differentiates blood cell development to form a variety of diverse cells such as erythrocytes, leukocytes, and thrombocytes [14]. A myeloid stem cell is an example where a stem cell may differentiate into different types of leukocytes, e.g., white blood cells such as granulocytes or monocytes, but never erythrocytes or platelets [15].

As mentioned above, during embryogenesis, stem cells form aggregates referred to as germ layers [16]. Once hESCs differentiate into a specific germ layer, they become multipotent stem cells and can only differentiate according to their respective layer. Pluripotent stem cells are present throughout the life of any organism existing as undifferentiated cells [17]. Regulatory signals influence stem cell specialization to create specific tissues that are produced via physical contact between cells through the microenvironment/stroma or as stimulators in the form of cytokines, interleukins, and/or tissue factors secreted by surrounding tissues. These factors from internal sources are controlled via the presence of the genome, i.e., genes, thus DNA acting through transcription translation reactions [11]. Stem cells provide a mechanism designed to function as the bodys internal repair system. For as long as an organism remains functional, its stem cells will continue to provide differentiation pathways to replace more mature cell lineages. This is the repair and replenishment aspect of stem cell vitality [11, 18].

The growth and development of an organism depends on the presence of stem cells. Overall, somatic stem cells such as ESCs can be distinguished based upon their characteristic lineage line of development. ESCs can be derived without isolating them from the inner cell mass; however, their growth potential is limited [11]. ESCs can be propagated in vitro using tissue culture conditions indefinitely without restriction if their growth requirements are maintained [19, 20]. ESCs can be propagated in culture with appropriate culture medium containing essential nutrients [19]. Passage of ESCs is an adequate method of sub-culturing stem cells to propagate their numbers over time. Because ESCs are totipotent, they can differentiate into every cell type required in any organ cell system [21]. However, because totipotent stem cells demonstrate immortality, ethical restrictions restrict the procurement of these cells. The origin of these totipotent stem cells is from the ICM of the blastocyst present in embryos. Thus, the procedure to obtain them destroys the viability of that embryo from further development. However, most ESCs are derived from fertilized eggs in an in vitro clinic rather than from eggs harvested from pregnant women [22].

Among the many stem cell types that exist are as follows:

Hematopoietic stem cells have the potential to differentiate into many types of blood cells, e.g., erythrocytes, leukocytes, and thrombocytes.

Mesenchymal stem cells are found in multiple types of tissues. They can differentiate into multiple lineages such as bone, adipose, vascular, and cartilage tissue. They can be harvested from sources including but not limited to the umbilical cord, bone marrow, and endometrial polyps [23].

Neural stem cells develop into glial or neuronal cells such as nerve cells, oligodendrocytes, and astrocytes. These cells have been used in treatments regarding Parkinsons disease through transplants [24].

Skin stem cells (SSCs) consist of several types that are separated into their own niches including hair follicle stem cells, melanocyte stem cells, and dermal stem cells. SSCs have greater potential to be used for stem cell therapies and treatments since these cells can differentiate into more cell lineages [25].

Human ESCs are involved in whole-body development and can eventually become pluripotent, multipotent, and unipotent stem cells. Compared to adult somatic stem cells, they also have a quicker proliferation time and greater range of differentiation causing them to be more ideal and preferred in therapies [26].

Stem cells can also be taken from the placenta. Placental fetal mesenchymal stem cells can differentiate into a wide variety of cells and are abundant, not requiring invasive procedures to procure. They are not surrounded with ethical issues that ESCs have since the placenta is usually considered medical waste after birth, making it favorable for use as treatment. They can produce ectodermal, endodermal, and mesodermal lineages in vitro and contain the same cell markers as ESCs, making them very similar. Placental stem cells are pluripotent and have low immunogenicity which allows them to be ideal for therapies and treatments [27].

Differentiation was thought to be restricted and non-reversible. However, after several major experiments through cloning, even differentiated cells can be reprogrammed or induced to be pluripotent. Two major cloning-related discoveries were made in 1962 and 1987. The first was done by John Gurdon who cloned frogs through the process of somatic nuclear cell transfer (SNCT) into an enucleated frog egg [28]. This showed that the nucleus of a specialized somatic cell could be reverted and develop cells that could eventually produce an entirely new organism [29]. The specialized somatic cell became pluripotent which, before this experiment, was thought to be impossible [30, 31]. This technique was famously used successfully in the cloning of Dolly, the sheep [28]. The 1987 experiment focused on gene expression. The forced expression of one gene, known as myogenic differentiation 1 (Myod1), could cause fibroblasts to turn into myoblasts [32]. This was another example of transforming cells, but this was done through programming the cell in the DNA.

These discoveries provided the turning point in stem cell research by advancing the therapeutic application of stem cells when a Japanese team of scientists showed adult multipotent stem cells could be reverted into a pluripotent state. These cells functioned like ESCs but did not need to be acquired from embryos. This discovery created a process to avoid endangering the life of a fetus to obtain ESCs. The determining factor in the process using murine fibroblasts was incorporating a retrovirus-mediated transduction system containing four transcription factors found in ESCs known as Oct-3/4, Sox2, KLF4, and c-Myc [17]. These factors induced the fibroblasts to become pluripotent. The newly formed reprogrammed stem cells were named induced pluripotent stem cells (iPSCs). A later study succeeded using human cells [33]. This technological breakthrough created a new line of research in stem cell biology that coincided with the generation of iPSC cell lines. Importantly, as mentioned, iPSCs can be made biocompatible with any patient, thus dramatically improving the therapeutic potential of this newly created cellular therapy [13]. ESCs are still the only naturally occurring pluripotent cells, but from these experiments, terminally differentiated cells can be induced into pluripotency to become iPSCs. Still, reprogramming cells comes with risks to cellular development due to histone alteration. However, an experiment was done by sequencing DNA from murine iPSCs and confirmed that although mutations were introduced, reprogramming cells could create iPSCs that were not seriously genetically affected or produce ill-functioning cells [11, 34].

As these cells are manufactured, controlling the quality of iPSC lines is necessary for use as treatments. Ways that they are controlled for their quality are as follows (Table 1) [35]:

Different ways that stem cells can be verified and tested during growth to ensure their quality and viability.

A common source for iPSCs includes fibroblasts. Especially in treatments, taking the patients own fibroblasts for the treatment has shown to be beneficial as the autologous cells do not risk being rejected. However, at first, they were the only source that could be used, and obtaining these cells required a biopsy. Thus, further research was conducted to enhance the techniques efficiency. Other cell types have also been reprogrammed, but fibroblasts are still preferred since their stimulation can be fast and controlled [36, 37].

Stem cells are only potentially useful if they can be differentiated into specific lineages. If not, they can form a teratoma in vivo. However, this condition can be regulated; therefore, if the process can be controlled, it allows clinicians and researchers to improve their therapeutic use when using specific signaling pathways for differentiation. In regenerative medicine, it is important to ensure that these cells will then differentiate in a timely and efficient manner. Directed differentiation exists to push the ESCs to differentiate. As cells develop, they send out signals within their surroundings [38]. Messages from the extracellular environment can also control the differentiation of stem cells which has been shown in in vitro cultures [39]. This can be done easily in in vitro cultures by controlling the conditions in culture. However, replicating such environments in vivo, has been challenging, requiring strict culture conditions [11].

For hESC treatments to be used on patients, the therapies must be culture-free, meaning the stem cells are not contaminated with any feeder or animal cell components [40]. The FDA requires this pertaining to procurement and storage of any type of stem cells contemplated for human use [41]. A difficulty in procuring these treatments is that great amounts of these cells used for treatment must be cultivated in the absence of feeder cells.

Directed differentiation protocols replicate the development of the ICM during embryogenesis. Pluripotent stem cells differentiate into derived progenitors from each of the three germ layers, just as is observed in vivo. Specific molecules act as growth factors to induce stem cells to become specific progenitor cells eventually to develop into a specific cell type. Growth factors function as important regulatory molecules that affect germ layer development in vivo; examples include bone morphogenic proteins (BMP) [42, 43], fibroblast growth factors (FGFs) [44], transcription factors of the Wnt family [45], or transforming growth factors-beta (TGF). How each factor influences germ cell differentiation is unclear and research is ongoing.

The concentration levels and duration of action of a targeted signaling molecule such as a growth factor produces a variety of outcomes. However, the high cost of recombinant molecules currently restricts their routine use in therapy limiting their clinical application. A more promising approach is to focus on using small molecules, thereby activating or deactivating specific signaling pathways [46]. These methods are effective in improving reprogramming efficiency by helping to generate cells that are compatible with the target tissue type. Also, they offer a more cost-effective and non-immunogenic therapy method [47]. Endogenously generated small molecules, e.g., retinoic acid is effective for patterning nervous system development in vivo. It functions effectively in embryonic development where it is used in vitro in culture systems to induce the differentiation of somatic cells [48, 49]. These cells can also induce retinal cell formation when hESCs are used [50]. Through the control of biochemical signals and the environment as important factors can be essential to achieve optimal hESC differentiation when culturing stem cells.

Culture systems have been regulated by multiple agencies around the world including the Food and Drug Administration (FDA) and the European Medicine Agency (EMA). Initially, animal-derived products were utilized, however, that introduced possible animal pathogens. Some stem cell lines derived from embryos and human feeder cell lines have been established which include stem cell-derived cardiac progenitors and mesenchymal stem cells. Xeno-free culture systems also include the development of human foreskin fibroblasts (HFFs) [11, 51, 52, 53].

Stem cells hold immense promise as an important therapeutic option for the future of medicine. Beyond their crucial role in regenerative medicine, stem cell research has demonstrated their intricate processes when involved in growth development. In stem cells, DNA is loosely organized, allowing genes to remain active. Differentiated cells differ in that these cells deactivate certain genes and activate others that are essential to the signals that the cell receives. This process is reversible, demonstrating that pluripotency can be induced through specific gene modifications. Several core transcription factors including Oct3/4, (SRY)-box 2, and Nanog genes have been found to keep these cells pluripotent [17, 54]. Nuclear transcription factors Oct3/4 and Sox2 are crucial for producing iPSCs [54].

Presently, various therapies using stem cells are offered as treatments for conditions like spinal cord injuries, heart failure, retinal and macular degeneration, tendon ruptures, and type 1 diabetes [52, 55, 56, 57, 58]. Stem cell research improves our understanding of stem cell physiology, potentially leading to new treatments for presently untreatable diseases. Many of which are dermatological disorders which were previously thought to have no good solution. This chapter focuses on the application of stem cells treating various dermatological disorders and compliments recent reviews on the same topic [11, 59].

Stem cell therapy has not been actively used as a solution for restoring hair growth, but current results are promising. One study used harvested autologous adipose-derived stromal vascular cells through injected into the scalp of 20 patients with alopecia areata (AA) [60]. At three and six months of follow-up, all patients produced statistically significant hair growth. Adipose-derived stem cell conditioned medium (ADS-CM) contains growth factors essential for hair follicle regrowth such as basic fibroblast growth factor, hepatocyte growth factor, platelet-derived growth factor, vascular endothelial growth factor, and transforming growth factor-beta (TGF-) [61]. Another study isolated human adult stem cells by centrifuging human hair follicles obtained through punch biopsy and injected them into the scalps of 11 androgenetic alopecia (AGA) patients resulting in an increase in hair density and count compared to baseline and placebo [62]. In a larger study with 140 AGA patients, autologous cellular micrografts containing HFSCs were used as a treatment. Within one session, over two-thirds of the patients showed positive results while there was significant increase in their regrowth and thickness [63, 64].

A study randomly assigned 40 patients (20 with AGA and 20 with AA) to receive either autologous bone marrow-derived mononuclear cells or autologous follicular stem cell injections into the scalp, found significant improvement in hair loss with no significant difference between the two preparations [65]. An investigation introduced a novel stem cell method, termed stem cell educator therapy in which patients mononuclear cells are separated from whole blood and allowed to interact with human cord bloodderived multipotent stem cells, thus educating these stem cells after returning them to patients [61]. In nine patients with severe AA, all but one experienced improved hair regrowth of varying degrees. Two patients (one with alopecia totalis and one with patchy AA) experienced complete hair regrowth at 12weeks without relapse after two years. A combination of platelet-rich plasma and stem cell technology also showed promising results [61].

Numerous murine studies have demonstrated the progression of allergies in atopic dermatitis (AD) can be inhibited by using umbilical cord blood mesenchymal stem cells (UCB-MSCs), bone marrow mesenchymal stem cells (BM-MSCs), or adipose-derived mesenchymal stem cells (AD-MSCs) [66, 67, 68, 69]. It is important to consider the type of stem cell used, the number of cells transplanted, the preconditioning of the cell preparation, the therapys relevant targets, and the route and frequency of administration. One example highlighting the complexity of stem cell-based therapy was shown in a study where human UCB-MSCs were pre-treated with mast cell granules [68]. This pre-treatment method enhanced their therapeutic effectiveness, as evidenced by the reduced signs of AD in a NC/Nga mouse model. It was found that hUCB-MSCs primed with mast cell granules were more effective in suppressing the activation of mast cells and B lymphocytes compared to nave MSCs, both in vitro and in vivo [70].

Despite promising results from murine studies in AD, only a few clinical trials have been conducted. In one study, a single subcutaneous administration of hUCB-MSCs was given to 34 adult participants with moderate-to-severe AD [66]. The improvement in AD symptoms was measured using the eczema area and severity index (EASI) score. Treatments for both low and high doses of hUCB-MSCs showed symptom improvement. In the higher dose group, six out of 11 subjects experienced a 50% reduction in EASI score, with no reported side effects. Additionally, typical biomarkers of AD, such as serum IgE levels and the number of eosinophils, decreased after treatment.

A later clinical trial had the injection of clonal mesenchymal stem cells (MSCs) into five patients with atopic dermatitis (AD) who had not responded to conventional treatments [71]. Patients received either one or two cycles of MSC treatment. Effective treatment was evaluated using cytokine biomarkers (CCL-17, CCL-22, IL-13, IL-18, IL-22, and IgE) and EASI scores. Results showed four out of five patients achieved more than a 50% reduction in EASI scores after one treatment cycle. Additionally, significant decreases in IL-13 and IL-22 levels were observed with other biomarkers showing decreasing trends during the studies.

In a more recent phase 1 clinical trial published in 2024, 20 subjects were treated intravenously with human clonal MSCs, given a low dose of cells in Arm 1 and a higher dose in Arm 2. There was an overall improvement for both arms, and the difference in dosage did not make a statistically significant effect. A phase 2 trial proceeded and was randomized, double-blind, and placebo controlled. In this, 72 subjects were tested. The half given the treatment were given the high dosage of hcMSCs originally tested in phase 1. Compared to the placebo group, the treated group had a statistically significant improvement response [72]. These findings suggest MSC administration might help normalize the immune system in AD patients. However, further studies are needed to understand the long-term mechanisms and effects of MSC treatment in this context.

Dermatomyositis remains a mystery with its exact etiology still unknown. Research using stem cells to treat the disease is limited with few studies and case reports available. One report detailed successful autologous stem cell transplants for two patients with juvenile dermatomyositis who had not responded to initial treatments [73]. In the first patient, the procedure involved transferring CD3/CD19-depleted mobilized peripheral blood mononuclear cells (PBMCs), which included 7.5106/kg CD34+ stem cells and 2.9104/kgT cells. Following a 26-month follow-up period, significant improvements were observed. The Childhood Myositis Assessment Scale (CMAS) score increased from 6 to 51and the manual muscle testing (MMT) score rose from 61 to 150. These results demonstrated a substantial improvement in symptoms with the patient regaining the ability to walk and showing significant reductions in inflammatory reactions after the autologous stem cell transplant.

In the second patient, a similar response was observed. The patient was treated with CD3/CD19-depleted autologous PBMC graft (7.51106/kg CD34+; 1.6104/kg CD3+). After three months of treatment, the patient had less muscle pain and contractures, and she began also regained the ability to walk [73].

An uncontrolled study in which 10 patients received allogenic mesenchymal stem cell therapy was reported where one or two MSC infusions were given to patients depending on whether they had disease recurrence within a short time after initial treatment. Out of the 10 patients, eight showed significant clinical improvement, with their symptoms improving after MSC therapy [74]. However, further research is required to evaluate the long-term effects of MSC treatment in patients with dermatomyositis.

Epidermolysis bullosa (EB) is a genetic condition that currently has no treatment, but stem cell therapy is one cell-based therapy under investigation that may be able to correct the skin and its underlying genetic component. Autologous or allogenic stem cells are options that can be used, with mesenchymal stem cell therapy showing potential; therefore, they may be more useful in alleviating some symptoms when tested in additional studies.

One study followed two patients with severe generalized recessive dystrophic epidermolysis bullosa (EB) treated with intradermal administration of allogenic mesenchymal stem cells from bone marrow showed complete healing of ulcers around the treated site by 12weeks [75]. Type VII collagen was detected along the basement membrane zone and the dermal-epidermal junction was continuous in the treated site 1week after treatment. Unfortunately, the clinical effect lasted for only 4months in both patients.

In the case of junctional EB treated with primary cultured keratinocytes, it showed normal morphology and the absence of spontaneous and induced blisters or erosions at 21months of follow-up [76]. Studies using BMSCs to treat recessive dystrophic EB have also shown promise [77, 78]. One study investigated 10 recessive dystrophic EB children treated with intravenous allogeneic bone marrow-derived mesenchymal stem cells and found that the procedure was well tolerated with minimal side effects over the nine-month period [79]. However, skin biopsies performed at the two-month time point showed no increase in type VII collagen and no new anchoring fibrils. While the initial clinical improvement was favorable, it was not maintained over time due to insufficient production of durable proteins like collagen and laminins. The current evidence for stem cell therapy in treating EB is limited because few patients have been treated. This underscores the need for additional research to assess the therapys effectiveness and the balance of its risks and benefits [80].

Despite significant progress in understanding psoriasis pathogenesis in recent years, it remains unclear what is the exact etiology. Current research suggests that dysfunction in certain types of stem cells might be a primary cause of the inflammatory response dysregulation in psoriasis [81]. This hypothesis came after observing long-term remission in psoriasis patients who underwent hematopoietic stem cell therapy [82, 83]. Conversely, there have been reports of acquired psoriasis in patients who received bone marrow transplants from donors with psoriasis, indicating a significant role of hematopoietic stem cells in disease pathogenesis [84, 85]. MSCs have also shown success in treatment likely due to their engraftment, paracrine, or immunomodulatory effects [86]. However, the availability of cost-effective and safe alternatives limits the use of stem cell transplantation as a practical option for treating psoriasis.

Scleromyxedema is a chronic fibro-mucinous disorder that can result in respiratory complications. A study conducted on five patients who underwent high-dose chemotherapy followed by stem cell rescue led to durable remission in most cases, although it did not cure the disease [87]. Another study showed scleromyxedema was successfully treated with chemotherapy and autologous stem cell transplantation [88]. The patient achieved complete recovery within six months and remained in remission for 3years post-transplantation. In a 2022 report, a male patient underwent an autologous hematopoietic stem cell (HSC) transplant after previous therapies failed to improve his symptoms. Improvements were seen in the patients skin, but the renal and pulmonary complications required the use of steroids and plasmapheresis. Unfortunately, the patient contracted SARS-CoV-2 virus and died [89]. More studies still need to be done to determine if stem cell therapy might be useful alone or combined with other therapies to treat scleromyxedema.

Systemic sclerosis (SSc) is an autoimmune disease characterized by excess collagen in the internal organs and skin, causing ulcers and organ damage. HSC therapy and MSC therapy have been tested and found to improve pain, blood flow, lung function, among other symptoms of the disease [90]. Autologous hematopoietic stem cell therapy is preferred over allogeneic therapy due to its lower treatment-related mortality and absence of graft-vs.-host disease [91].

Stem cell therapy has been extensively studied in three randomized controlled trials: the American Scleroderma Stem Cell versus Immune Suppression Trial (ASSIST, phase 2, 19 patients), the Autologous Stem Cell Transplantation International Scleroderma Trial (ASTIS, phase 3, 156 patients), and the Scleroderma Cyclophosphamide or Transplantation study (SCOT, phase 3, 75 patients), with several pilot and case studies [92, 93, 94]. These studies have demonstrated autologous hematopoietic stem cell therapy is an effective and safe treatment for systemic sclerosis. However, patients with severe major organ involvement (pulmonary, cardiac, or renal) or serious comorbidities were excluded from all three trials due to contraindications [59].

MSC therapy has the ability to suppress innate and adaptive immunity and can differentiate into a wide variety of tissues, making it seem like an ideal choice for SSc [95]. However, if donors are not carefully chosen, there is the chance that collagen production can be increased, thus this therapy can worsen symptoms [96]. This research suggests that autologous MSCs from patients that have advanced stage SSc should not be used for treatment. On the other hand, allogenic MSC therapy has lived up closer to the promises of stem cell therapy. Allogenic MSCs were administered intravenously in a female patient, where her skin condition improved, reducing the appearance of ulcers and her pain score [95]. In a clinical trial, combining MSC therapy with plasmapheresis was shown to improve lung function and skin thickness shown in improved modified Rodnan Skin Scores. The current research suggests that MSC therapy may be most effective when paired with another therapeutic option, but research still needs to be done to explore this.

Stem cell therapy has been found to be more effective than conventional immunosuppressive drugs and is currently the only disease-modifying strategy that improves long-term survival, prevents organ deterioration, enhances skin and pulmonary function, and improves overall quality of life.

The European Society for Blood and Marrow Transplantation (ESBMT) and the British Society of Blood and Marrow Transplantation (BSBMT) classify autologous hematopoietic stem cell therapy in severe resistant cases as a clinical option, requiring a risk-benefit assessment [97, 98]. Guidelines from the American Society for Blood and Marrow Transplantation (ASBMT) categorize this therapy as standard of care, rare indication for children (indicating it is an option for individual patients after careful risk-benefit evaluation) and developmental for adults [98]. Patients with acute onset rapidly progressive disease refractory to conventional therapy and mild initial organ damage carry a better prognosis after HSC therapy. Patients with long standing conditions, indolent course and/or irreversible organ damage are contraindications to this therapy [99]. Thus, the challenge is to identify patients who are likely to be benefitted with HSC therapy.

HSC therapy has been tested in patients with refractory systemic lupus erythematosus (SLE). Many observational studies and clinical trials have been aimed at assessing the effectiveness and safety of this transplant approach [100, 101, 102]. In a long-term follow-up of a female patient who underwent allogenic BM-HSC treatment, her systemic lupus erythematosus disease activity index (SLEDAI) score was found to improve, pain improved, and engraftment remained functional [103]. Collectively, these reports show HSCs to be beneficial for patients with a shorter duration of refractory disease suggesting that earlier intervention might lead to better outcomes [104].

The therapeutic potential of MSCs has been investigated for various autoimmune diseases including SLE [105]. In a recent study, six refractory SLE patients were treated with an intravenous infusion of MSCs. Five of the patients reached the threshold for improvement, achieving an SLE Responder Index (SRI) of 4 [106]. In a separate long-term follow-up study done in 2021, 81 patients were treated with allogenic BM-MSC and/or UC-MSCs. After 5years, 37 patients had achieved clinical remission. MSC therapy has been shown to improve patient survival and reduce the severity of the disease as it has been shown to be safe and effective in treatments [107]. MSCs have been shown to alleviate SLE severity, improve renal function, decrease autoantibody production, upregulate peripheral T-cells, and restore balance between Th1- and Th2-related cytokines [108]. These collective immunomodulatory and regenerative properties position MSCs as a promising treatment for SLE.

Steroid topical treatment is the first line of therapy for vitiligo, but when it proves ineffective, surgical options may be viewed next [109, 110]. Cellular grafts using autologous non-cultured outer root sheath hair follicle cell suspension (NCORSHFS) have been tested as a method to treat vitiligo [111]. This method utilizes the regenerative capacity of hair follicle melanocytes, as they can repigment areas where vitiligo has caused depigmentation by allowing melanocyte precursors to proliferate into the areas that lack melanocytes, making them preferable over epidermal melanocytes for cell-based vitiligo treatments. One study reported NCORSHFS achieved an average repigmentation rate of 65.7%, with more than 75% repigmentation observed in nine out of 14 patients [112]. Another study investigated factors affecting therapeutic outcomes in 30 patients with 60 target lesions treated with NCORSHFS [111]. They found that 35% of the lesions achieved repigmentation greater than 75%. The study showed patients who achieved optimal repigmentation had significantly higher numbers of transplanted melanocytes and hair follicle stem cells. Also, the absence of dermal inflammation was a significant predictor of successful repigmentation. These results emphasize the importance of specific cellular components, and a favorable dermal environment is necessary for the effective treatment of vitiligo with NCORSHFS.

Another promising stem cell treatment for vitiligo is multilineage-differentiating stress-enduring (MUSE) cells [113]. In three-dimensional skin culture models, ex vivo studies have identified factors that encourage MUSE cells to differentiate into melanocytes. The melanocytes are integrated into the epidermis, promoting melanogenesis. However, the impact of MUSE cells in vivo remains to be determined [114].

Chronic or non-healing skin wounds present an ongoing challenge in advanced wound care. Current wound healing treatments remain insufficient. Stem cell therapy has emerged as a promising new approach for wound healing using MSCs [115]. MSCs are an attractive cell type for cell-based therapy due to their ease of isolation, vast differentiation potential, and immunomodulatory effects during transplantation. MSCs are known to play a key role in the wound healing process making them an obvious candidate for clinical use. When introduced into the wound bed, MSCs have been shown to promote fibroblast migration, stimulate extracellular matrix (ECM) deposition, facilitate wound closure, initiate re-epithelialization, enhance angiogenesis, and mitigate inflammation in preclinical animal models. MSC efficacy and safety use for the treatment of chronic wounds was further confirmed by several clinical studies involving human subjects which yielded similar positive results with no adverse side effects [116]. However, while MSCs appear to be a promising resource for chronic wound care, additional studies are needed to determine optimal cell source and route of delivery before this treatment can be recommended for clinical use.

MSCs for the treatment of chronic wounds has proven to be feasible, effective, and safe, reported through preclinical and clinical trials [117]. MSCs stimulate the healing process in chronic wounds through several biological and molecular mechanisms. One of the primary roles of MSCs is to promote the directional migration of fibroblast cells to the injury site where they can localize in the wound bed [115, 118]. Once localized fibroblasts facilitate wound closure and synthesize the necessary components of the ECM such as collagen. MSCs can also downregulate MMP-1, a type of collagenase primarily responsible for ECM degradation. MSCs function to preserve ECM and maintain dermal structure. MSC-treated wounds have increased elastin levels which provides recovering tissue with resiliency that is not typically seen in normal wound healing [116]. MSCs play a role in the re-epithelialization process by activating the proliferation, differentiation, and migration of keratinocytes that support the formation of a multi-layered and well-differentiated epidermis [117, 119].

MSCs are believed to stimulate the development of new hair follicles and sweat glands, which suggests these stem cells are capable of not only accelerating wound healing but also improving the quality of wound healing. MSCs use for chronic wounds supports angiogenesis by upregulating VEGF and Ang-1 increasing microvessels throughout the wound bed [120]. This allows the nutrient and oxygen transport to developing cells enhancing their longevity. Also, MSCs help to modulate the wound environment and in turn support proper healing by mitigating inflammation at the site of injury. Importantly, MSCs decrease infiltration of inflammatory cells and pro-inflammatory cytokines and initiate the polarization of M1 macrophages to anti-inflammatory M2 macrophages. MSCs also downregulate ICAM1, a protein involved in inflammation, and upregulate superoxide dismutase, an enzyme which breaks down harmful superoxide radicals [118, 121]. By supporting wound healing MSCs by optimizing the healing environment can produce efficient wound closure.

Several clinical trials in human subjects have generated positive results when MSCs were applied to chronic or non-healing wounds [122]. No adverse side effects have been observed which confirms the safety and feasibility of this cellular therapy for human application. However, further research is needed to determine the best cell source and route of delivery before this procedure can be recommended for human use clinically.

MSCs can be isolated from various tissue types including bone marrow, adipose tissue, cord blood, and placenta. MSCs demonstrate unique properties. Several comparative studies have reported MSCs as the most promise for cell therapy due to their abundance and ease of isolation as well as their regenerative and immunomodulatory properties [123]. How these MSCs are delivered into the wound is the critical question. MSCs can be delivered locally to the wound bed via injection, topical application, or incorporation into a 3D scaffold to avoid issues related to low engraftment efficiency observed following IV injection [124, 125]. Investigating local delivery methods, MSCs seeded into a biomaterial scaffold appears to hold promise as it allows for the localization of the cells into the wound bed and provides donor cells with protection and structure [126, 127]. Following additional research, the application of MSCs for chronic or non-healing wounds could provide a major development in advanced wound care.

Epidermal stem cells have potential to regenerate the epidermis and differentiate under appropriate stimuli into various skin cell types and tissues [128]. This property can be used to initiate and accelerate healing of chronic non-healing wounds. MSCs promote wound healing by decreasing inflammation, promoting angiogenesis, and decreasing scarring [129]. One study successfully applied human MSCs to non-healing and acute wounds using a specialized fibrin spray system [130]. Another study demonstrated the efficacy of stem cell therapy in diabetic foot ulcers [131].

Read more:
Stem Cell Use to Treat Dermatological Disorders - IntechOpen

Skin Stem Cells Comments Off on Stem Cell Use to Treat Dermatological Disorders – IntechOpen | March 1st, 2025

Scientists have managed to reprogram human skin cells directly into cells that look and act like embryonic stem (ES) cells. The technique makes it possible to generate patient-specific stem cells to study or treat disease without using embryos or oocytes--and therefore could bypass the ethical debates that have plagued the field.

Originally posted here:
Researchers Turn Skin Cells Into Stem Cells | Science | AAAS

Skin Stem Cells Comments Off on Researchers Turn Skin Cells Into Stem Cells | Science | AAAS | March 1st, 2025

Covering an average surface area of 1.85 m2, and accounting for ~15% of total body weight, the skin is considered the largest organ in the human body. Its primary function is that of a physical barrier against microbial pathogens, toxic agents, UV light, and mechanical injury [1]. However, this function can also extend into other vital functions, such as thermoregulation, protection against dehydration, and the excretion of waste metabolites [2]. Moreover, the skin also represents a major metabolic site, yielding a broad range of biomolecules, e.g., vitamin D [3].The skin is composed of two main layers, i.e., the epidermis and the dermis. Previously, another layer had been described within the skin, i.e., hypodermis [4]; however, there is an ongoing controversy in this regard and the hypodermis is now considered as part of the dermis. The skin contains accessories, such as hair, nails, and sweat, and sebaceous glands [5]. In addition, the skin is also populated by nerve receptors that can be triggered by external stimuli (e.g., touch, heat, pain, and pressure) [6]. The skin layers have different thickness according to their anatomical location; for example, the epidermis can be very thin in the eyelids (0.1 mm) whereas it can be thicker in the palms and soles of the feet (1.5 mm). In contrast, the dermis can be ~3040 times thicker in the dorsal area than the corresponding epidermal layer [2].The epidermis can be further sub-divided into strata with a unique cell composition, i.e., keratinocytes, dendritic cells, melanocytes, Merkels cells, and Langerhans cells. These epidermal layers are known as stratum germinativum, stratum spinosum, stratum granulosum, stratum lucidum, and stratum corneum. The first of these strata, also known as the basal cell layer, conforms the inner-most part of the epidermis [2,7]. It is in this layer that different populations of stem cells (SCs) are located, and which, through extensive proliferation and differentiation, provide the great regeneration capacity of the skin and enable the generation of auxiliary structures, e.g., nails and sweat glands [8]. It must be mentioned that the basal cell layer is not the only stem cell niche within the skin as these cells can also be found within the hair follicle (HF), interfollicular epidermis (IFE), and sebaceous glands [8], all of which are contained within the basal layer itself. The stem cells within the skin are usually named after the niche in which they reside in, i.e., hair follicle stem cells (HFSCs), melanocyte stem cells (MeSCs), interfollicular epidermis stem cells (IFESCs), and dermal stem cells (DSCs). Regardless of their niche, these cells are collectively known as skin stem cells (SSCs) (Figure 1).The main task of these SSCs is to replace, restore, and regenerate the epidermal cells that may have been lost, damaged, or have become pathologically dysfunctional [9,10]. For such end, a carefully orchestrated cell division, both symmetrical and asymmetrical, is required to both maintain the stem cell pool and produce lineage-committed cell precursors [11]. Initially, SSCs were thought to be age-resistant, mostly because their number does not seem to dwindle through time [12,13]. However, despite their longevity, SSCs eventually become unstable or dysfunctional and display a lower differentiation and self-renewal capacity [14].As previously mentioned, SSCs are found in diverse niches within the skin, of which the hair follicle has been the most studied. The distinct anatomical zones of the HF can house different stem cell types, such as HFSCs and MSCs [15,16]. The bulge region of the HF contains different stem cell populations; however, the exact identity of these cells is still unclear. Regardless, the presence of both proliferative (CD34+/LGR5+) and quiescent (CD34+/LGR5) stem cells has been described in previous research [16,17].Overall, the diverse subpopulations of SSCs have specific characteristics that set them apart from one another. For instance, HFSCs are mostly quiescent until triggered by several factors secreted by their progeny and by adjacent dermal cells [18]. Regarding the former, their isolation has been so far complicated by the lack of specific markers to identify them [19]. In addition to the hair follicle bulge, SSCs can also populate the sebaceous glands; however, these stem cells are thought to be unipotent and dedicated exclusively to the renewal of the sebocytes pool [16,20]. Other proposed niches are found within the compartments of the dermal papilla (DP) and the dermal sheath (DS) [9,16] and, unlike the stem cells located in the sebaceous gland, those located in both the DP and DS display a greater differentiation capacity, even being able to differentiate into cells of hematopoietic lineages [9], and have also been involved in the maintenance and repair of the dermal tissue. Melanocyte stem cells (MeSCs) are also located in the bulge and hair germ of the HF. Interestingly, their proliferation and differentiation seem to be closely tied to that of HFSCs [21]. Therefore, the concurrent activation of both MeSCs and HFSCs by the signals originating from the latter is hardly surprising. Due to their embryonic origin (i.e., neural crest), MeSCs possess high proliferative and multipotent capacity, which makes them interesting for regenerative medicine [22] and stem cell-based therapies [15,23]. In this regard, dermal stem cells (DSCs) are also considered as an accessible and abundant source for stem cell-based therapies [24] as they display great plasticity and the potential to differentiate into cells of ectodermal, mesenchymal, and endodermal lineages [24,25]. Consistently, the niche of these cells has been localized to the DP and DS [26]. IFESCs, on the other hand, are difficult to isolate and identify due to their unclear location within the basal layer. Therefore, their study has been mostly conducted through indirect means, such as screening with cell surface markers [27,28] or lineage analysis and tissue regeneration assays [29].Before delving further and in trying to bring greater clarity to the previous paragraph, let us recapitulate the existing models for skin stem cells that are currently being considered. The earliest model describing the hierarchy of stem cells in the interfollicular epidermis suggests the columnar arrangement of keratinocytes stacked in what is known as epidermal proliferative units (EPU) [30]. According to this model, stem cell clones are similar in size and their number remains rather constant during homeostasis. Relatively few basal cells have stem cell properties and can create transit amplifying (TA) cells, which constitute the majority of basal cells. This model suggests that TA cells go through several proliferation cycles before leaving the basal cell layer and follow their terminal differentiation program [31].Despite the seeming adequacy of this model, a relatively recent study showed that the size of epidermal clones increases over time, which contradicts the previous EPU model. Therefore, a stochastic model was proposed where the basal cells have inherent progenitor characteristics and their differentiation occurs at random. This apparent asymmetry in the cell population results in a scaling behavior in clone size and distribution. Thus, according to this model cell clones become fewer in number and have variable size [32]. Further, this model proposes the existence of a quiescent stem cell population with as few as four to six divisions per year and where progenitor cells present a balanced, although still random, differentiation pattern. However, one in five mitotic cycles would result in progenitor loss, thus suggesting that the population of both stem cells and progenitors might be heterogeneous and with different degree of competence [33].The validity of these theories was later tested in a mathematical simulation in which both the classical hierarchical model and the stochastic model described above would result in stem cell depletion [34]. Therefore, a third model proposed the existence of both a quiescent stem cell population and a committed progenitor population with stochastic differentiation fate [35]. Interestingly, this model could also explain the diminished healing capacity observed in the later stages of life, as the number of stem cells would decline with age. However, it must be kept in mind that all of these models are based in murine models and are not fully applicable in humans. Thereby, further research in this regard is still needed. Due to the extensive nature of this subject in particular, we suggest an excellent review by Dr. Helena Zomer et al. providing greater detail and context [36].

Due to the extensive and complex nature of the subject, the present review conveys a broad overview on SSCs, wound healing and the signaling pathways involved therein, as well as some of the current strategies in stem-cell based treatment strategies for wound healing.

More:
A Beginners Introduction to Skin Stem Cells and Wound Healing - MDPI

Skin Stem Cells Comments Off on A Beginners Introduction to Skin Stem Cells and Wound Healing – MDPI | March 1st, 2025

Skincare can be so confusing these days. With so many emerging ingredients on the market, it's hard to know which ones are right for you to prevent premature aging, repair damage, and keep your skin clear. Lately, we've seen ingredients like growth factors and exosomes have a moment in the spotlight, but there's another potent skin-renewal helper that we often forget about: stem cells.

According to board-certified dermatologist, stem cell scientist, and cosmetic surgeon Nathan Newman, MD, human stem cells aren't always ideal for use in skincare, because they may carry undesirable pathogens and genes, but plant stem cells don't have this issue and communicate almost identically to human ones.

Newman thinks that stem cells trump all the other options out thereand for good reason. I chatted with him about the difference between stem cells, exosomes, and growth factors to get the full picture. Keep reading for everything he had to share.

Newman broke down the difference between the industry's most popular youth-enhancing ingredients right now.

Exosomes: Exosomes are small vesicles that play a role in intercellular communication and tissue regeneration. They can be derived from stem cells, plants, or human cells. "They are usually processed and not used as they are produced by the cells," says Newman. "The products are unstable and need to be processed and preserved. They are not consistent from batch to batch, so each time it is manufactured, it will have a different set of signals."

Growth factors: Similar to exosomes, growth factors are proteins that play a key role in regulation cell growth and survival. They're already produced by various cells in the body, but many companies make synthetic versions to put into skincare formulas. These proteins signal molecules to promote cell proliferation, tissue repair, and the formation of new blood vessels. According to Newman, though, their effects are short-lived and do not always regenerate tissue. Basically, you can think of exosomes as a vehicle to deliver the message and growth factors as the actual message.

Stem cell factors: Plant stem cells, on the other hand, are the means by which cells communicate and impart their actions on other cells in your body. "The entirety of this cellular language is referred to as secretomes," explains Newman. "Some of these factors are released directly into the space in between cells and others need to be packaged, as they will be degraded outside the cell, and delivered from one cell to another cell. This cellular language is a dialogue between cells, and it sets off a domino effect that can influence thousands of cells in your body by what is referred to as paracrine effect (much like hormones do as part of your endocrine effect)."

Plant stem cells use a similar language to communicate as human cells. Plant-derived stem cell factors are also more accepted for use in skincare and don't carry the risks of communicable diseases as human cells do. Honestly, we don't see too many plant stem cellderived products out there on the market, and that's because the process of reproducing the same set of secretosomes from batch to batch is pretty difficult. But Newman has found a way to create an ideal set that helps the skin regenerate.

"For the first time, there is a patented process that allows the stem cells to be grown in such a way that it will not only produce a consistent set of factors, called Consortia Factors, but the process mentors the cells to produce a specific set of directions to direct the skin or hair to regenerate," he says. "In addition, this process allows the use of any cell, human or plant, to be used to produce Consortia Factors. Unlike exosomes, or isolated factors, Consortia Factors utilize a complex, synergistic network of bioactive molecules that mimic the skins natural healing and regenerative environment. This process allows for consistent and reproducible set of signals that can be studied and used for specific purposes, such as wrinkle correction, hair growth, skin tone [correction], etc."

Take a look below at what I'm using from Newman's stem cellrich line.

STEM Natural Intelligence

RePure Foaming Cleanser

This super-gentle cleanser is so easy on the skin and helps protect the skin's microbiome. It's also infused with stem cells that help preserve hydration and boost your skin's glow with antioxidants.

STEM Natural Intelligence

Stem Reset Moisturizing Facial Spray

This little spray is so handy for a refresh throughout the day, and it's so hydrating. It's another great tool to have in your toolbox for barrier repair because it contains moisturizing polysaccharides and antioxidant-rich gooseberry extract. It gives you a quick boost of serious moisture or is great to use as a setting spray.

STEM Natural Intelligence

Regenerative Serum

This is the crme de la crme of stem cellderived skincare. This serum contains the most stem cell factors out of the entire line and is designed to visibly reduce the appearance of wrinkles, promote even skin tone, and boost elasticity. It also help to support the production of collagen in the skin and floods it with antioxidants that give you a boost of radiance.

STEM Natural Intelligence

Stem Renew Day Cream

Containing a host of skin-perfecting ingredients, this day cream is lightweight and noncomedogenic yet still super hydrating. As with all of Stem's products, this cream contains a host of plant-based stem cells along with vitamin E, Coenzyme Q10, and gluconolactone to mildly exfoliate the skin.

STEM Natural Intelligence

Stem Revitalize Night Cream

The night cream is similar but contains niacinamide and bakuchiol extract to help with dark spots and increase cellular turnover. It also supports your body's anti-inflammatory response and is rich in vitamins A, C, D, E, and K.

The Stem Company

ReGlow Complexion

This was an immediate favorite from the brand after I received a facial with it at Newman's office. Like the name suggests, it gives you an immediate glow. My only complaint is that the bottle is super small and goes fast when you use it as often as I do.

Stem Natural Intelligence

ReLeaf Serum

This one is great for calming acne and inflammation because it contains adaptogens like ashwagandha along with antioxidants. It can also be used almost like a comforting balm to soothe aches and pains.

Lilfox

Flower Goo Botanic Ferment Stem Cell Serum

CLEARSTEM Skincare

Cellrenew Collagen Stem Cell Serum

Angela Caglia

Cell Fort Serum

Originally posted here:
Everything to Know About Stem Cells From a Dermatologist | Who What Wear

Skin Stem Cells Comments Off on Everything to Know About Stem Cells From a Dermatologist | Who What Wear | March 1st, 2025

The world of skincare has seen remarkable advancements over the years, with science-driven ingredients revolutionizing how we support skin renewal and repair. Among the most transformative discoveries are growth factors, stem cells, and exosomes each playing a crucial role in skin rejuvenation. But how do they differ, and how has this technology evolved over time? Lets break it down.

Epidermal Growth Factors (EGFs) are naturally occurring proteins that signal skin cells to regenerate, repair damage, and boost collagen and elastin production. In skincare, EGFs help accelerate healing, improve skin texture, and reduce the appearance of fine lines and wrinkles. They are particularly beneficial for aging and compromised skin, promoting a firmer, more youthful complexion.

Historically, the most potent growth factors came from human or animal sources. However, advancements in biotechnology have enabled the creation of lab-synthesized peptides that mimic the exact chemical structure of natural growth factors. These bioengineered peptides have been proven to accelerate skin renewal, smooth fine lines and wrinkles, enhance skin texture, and combat signs of environmental damage.

Stem cells are undifferentiated cells that have the unique ability to develop into various types of specialized cells. In skincare, stem cell extractstypically from plant or human sourcesare used for their rich composition of growth factors, peptides, and antioxidants that support tissue repair.

NeoGenesis, a pioneer in biotech-driven skincare, developed patented SRM technology that enables the harvesting of an array of molecules from multiple adult stem cell types and packages them in a highly bioavailable exosome delivery system. These powerful molecules include growth factors, cytokines, and other signaling proteins that are crucial for the bodys natural healing process. Their regenerative skincare products provide nutrients that mimic and enhance your bodys own natural stem cell function.

While growth factors are signaling proteins, stem cells act as a source of these growth factorsdelivering a broader spectrum of regenerative compounds that can enhance the skins natural repair mechanisms. Unlike single-function growth factors, stem cell released media works holistically to enhance skin resilience, making them ideal for sensitive, damaged, or aging skin. They support wound healing, improve hydration, and strengthen the skin barrier.

Plant-based stem cells provide an excellent source of antioxidants and anti-inflammatory benefits to keep skin protected from oxidative stress to promote renewal. However, they cannot communicate directly with live human stem cells to encourage regeneration.

Exosomes are tiny extracellular vesicles that act as advanced messengers, carrying a concentrated blend of antioxidants, nucleic acids, peptides, and phosphoproteins directly to cells. They transmit messages to a target cell and train that cell to act in a certain way. With this enhanced cell communication, in the skin, exosomes can accelerate repair and optimize collagen production for a more youthful, radiant appearance. Exosomes offer a more stable and potent alternative to traditional growth factors or stem cells, making them one of the most cutting-edge innovations in regenerative skincare.

( plated ) Skin Science is the first and only company to harness the power of platelet-derived exosomes in skincare and is a standout in biotech-driven skincare. Through years of research, they developed their patented Renewosome technology to deliver the power of platelet-derived exosomes in a shelf-stable serum formulated to regenerate the appearance of the skin. Their gentle extraction method preserves the structure, purity, and potency of the exosomes, ensuring stability for 12 months without refrigeration. ( plated ) Skin Sciences revolutionary technology is clinically proven to deliver targeted peptides and powerful antioxidants to support the production of collagen and elastin and improve the appearance of redness, brown spots, dullness, and wrinkles.

Platelets are the most prolific generators of exosomes.

As a first responder to wound sites, platelet-derived exosomes go directly to the area of damage and play a pivotal role in the skins natural regeneration process.

Exosomes deliver precise, self-regulating signals and naturally deactivate once their job is done, eliminating concerns of overproliferation.

Platelets act as the direct messengers of renewing cues rather than functioning as intermediaries, as with other regenerative cells or exosomes.

As compared to stem cell exosomes, it is easier to extract pure, regenerative cells and to control variables for consistency over time.

Exosomes can target multiple skin concerns simultaneously (e.g., aging, inflammation, and pigmentation).

Their ability to provide targeted cell-to-cell communication makes them the most advanced option for promoting long-term skin health.

Late 1990s Growth factors were introduced in topical skincare, derived from human and plant sources.

Mid-late 2000s Stem cells started appearing in skincare products as the potential for skin regeneration was realized and their role in cellular communication and repair was better understood.

2010 to Present Exosomes have emerged as the next generation of regenerative skincare, offering superior results in cellular repair and collagen synthesis.

( plated ) Skin Science Intense Serum: This revolutionary, advanced regenerative treatment utilizes a proprietary blend of platelet-derived exosomes to deliver next-level skin rejuvenation. It is clinically proven to enhance skin renewal and healing by delivering targeted antioxidants and peptides to improve tone, texture, firmness, elasticity, and overall skin health.

NeoGenesis Recovery Serum: This breakthrough healing serum utilizes patented SRM technology to restore skin to a healthy and radiant state, effectively correcting the most damaged skin. It is rich in stem cell-released molecules containing growth factors, antioxidants, proteins, and peptides to promote healing and improve the signs of aging while reducing redness and inflammation.

Rhonda Allison Radiant Renewal Serum: This serum uses powerful peptide epidermal growth factors (EGF) to directly stimulate the proliferation of skin cells, promoting renewal and encouraging a more youthful, revitalized complexion. It also provides strong antioxidant properties while reducing inflammation and brightening uneven pigmentation.

Le Mieux EGF-DNA: Enriched with proprietary epidermal growth factors (EGF), this concentrated serum repairs skin tissue and stimulates the skins own cell renewal properties to promote firmer, healthier, and more radiant skin.

With advancements in growth factors, stem cells, and exosomes, skincare continues to evolve toward more targeted, effective, and biologically intelligent solutions. While growth factors laid the foundation for regenerative skincare, exosomes are now leading the charge, providing unparalleled benefits in skin repair, hydration, and resilience.

See the article here:
Lets Talk Skin Rejuvenation: Growth Factors, Stem Cells, and Exosomes

Skin Stem Cells Comments Off on Lets Talk Skin Rejuvenation: Growth Factors, Stem Cells, and Exosomes | March 1st, 2025

Dr. Inta Gribonika in the lab at NIH

Everyones skin may be tougher than they realize. Research led by Dr. Inta Gribonika, a postdoctoral NIH fellow, demonstrates that skin is more than simply a cover from the outside world; it can offer a first line of defense against infection, paving the way for new kinds of therapies.

Gribonika recently completed a four-year stint as a visiting fellow in the Laboratory of Host Immunity and Microbiome at the National Institute of Allergy and Infectious Diseases (NIAID). During her time at NIH, she contributed new knowledge about the skins role in immune response, research that recently was published in Nature.

Her findings show that the skin can act as a lymphoid organ. In other words, a specific immune response can actually be primed in the skin.

Gribonika is a mucosal immunologist. Her doctoral research had focused on how an immune response could be induced in the gastrointestinal tract after vaccination. After reading that the bacteria living naturally on skin is coated in antibodies, she began to wonder how the body could generate antibodieswhich it normally would do against an infectionaround something thats generally harmless.

Up until now, we were thinking that B cellsthe lymphocytes that produce antibodieswere not living in the skin or coming toward the skin tissue at homeostasis, she said. Her experiments show that B cells do exist in healthy skin.

In the lab, Gribonika painted a beneficial bacterium, S.epidermidis, onto the skin of mice. This bacterium is commonly found on human skin, but not on mice.

I showed that, indeed, skin can recognize this new harmless member of microbiota and generate specific humoral immunity against it, she said. This can happen without any help from professional immune organs, such as the spleen or lymph nodes.

The antibody works as a barrier protection, Gribonika said. It works as a health insurance in case this one new member of commensal microbiota that we now acquired decides at some point in the future to become nasty and infect us.

The ability of harmless bacteria on the skin to stimulate an immune response without inflammation opens a world of possibility for topical medications and vaccines. They could be formulated in a cream that anyone could apply to the skin.

This route is so interesting because its noninvasive and you wouldnt need a clinical practitioner to help you apply the medicine, Gribonika said.

In reflecting on her time at NIH, Gribonika emphasized how much she enjoyed getting to know the people in the lab. Each investigator had his or her own project, but they all supported each other. And they came from all over the world, bringing their different cultures and perspectives, which she found especially enriching.

NIH is probably the best place on Earth to do research, she said. There are so many resources, and the community is so welcoming and willing to share.

When she arrived at NIH, Dr. Yasmine Belkaid was her lab chief. She described Belkaid as a visionary who encouraged her trainees to think big. She gave me the space and freedom to ask the questions I wanted to pursue, Gribonika said.

Gribonika studied biology at the University of Latvia in Riga.

Photo: Sergei25/Shutterstock

Gribonika first became interested in science at a young age. My mom and dad would always read to me about great discoveries and about the people who made them, she recounted. These stories sparked her imagination and got her thinking about nature and the world from different perspectives.

I got interested in science to question whats therewhat we can see and what we cant see, Gribonika said. Immunology is heavily focused on microscopy, on the things we dont see just by looking at our skin. But if you ask the right questions and use the right antibody to target the right thing, all of a sudden you see all these interesting things happening in and on the skin.

Gribonika is a native of Latvia, a small northern European country with less than two million people. As her friend Daina Bolsteins, an administrative assistant at NIAID who is also of Latvian descent, noted, Latvia is better known for producing basketball and hockey players, opera singers and symphony conductors than for producing scientists. Gribonika said she hopes her story will inspire other aspiring scientists from her country.

In March, Gribonika headed to Sweden to begin a new chapter as a tenure-track investigator at Lund University.

Her advice to young investigators? Never give up. Remember why you chose this path in the first place, she said.

If the data disproves your hypothesis, follow the data. If the data conflicts, repeat with other methods and protocols. Be cautious. Verify.

Such rigor in research, she said, opens the door to learning new concepts about the human immune system and overall health.

Results will take you to places you never thought of, she said. Theres a lot of novelty out there.

More here:
NIAID Fellow Uncovers the Skins Natural Immunity | NIH Record

Skin Stem Cells Comments Off on NIAID Fellow Uncovers the Skins Natural Immunity | NIH Record | March 1st, 2025

Edible Beautys Super Stem Cell Concentrate: The breakthrough skincare innovation thats revolutionising anti-ageing  7NEWS

Read more:
Edible Beautys Super Stem Cell Concentrate: The breakthrough skincare innovation thats revolutionising anti-ageing - 7NEWS

Skin Stem Cells Comments Off on Edible Beautys Super Stem Cell Concentrate: The breakthrough skincare innovation thats revolutionising anti-ageing – 7NEWS | March 1st, 2025