The Promising Field Of Stem Cells In Cutaneous Repair

  • Soumya Iyer International Baccalaureate, Natural Sciences, Global Schools Foundation

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Introduction

Brief overview of the skin's importance and its vulnerability to damage

The skin is the largest organ of the human body. It consists of 3 layers: epidermis, dermis and hypodermis. It serves as a barrier against UV light, microorganisms, physical trauma and water. Additionally, it plays an integral role in regulating body temperature and producing vitamin D with keratinocytes. Considering the skin has such essential functions in the body, any damage can lead to disruptions in many processes. Its delicate nature makes it prone to abrasions and other injuries which hinder its integrity and function.

Introduction to stem cells and their regenerative potential

Stem cells have the potential to differentiate into many cell types, making them a useful solution for many therapies. By exposing them to various agents and growth factors, we can manipulate their growth and use in different conditions. Additionally, they can self-renew, making them suitable for repairs.

Since stem cells have such a good capacity to renew, they are considered for use in cutaneous repair. This is especially important for burn patients for those with severe skin damage where the natural healing process is not useful and leaves scars.

Understanding cutaneous damage

Explanation of common types of cutaneous damage (wounds, burns, scars)

Some of the common forms of cutaneous damage include cuts, scratches and bruises. Cuts and tears are generally characterised as wounds that penetrate the skin till the adipose tissue (Fat tissue). Scrapes and scratches are usually surface-level, so they do not go through the skin, making them less serious. The third type of damage, like bruises, is caused by damaged blood vessels within the skin and is usually caused by blunt objects, unlike the other two.

The skin's natural healing process and its limitations

The skin has its natural healing processes for damage. These damages are usually classified into acute and chronic, where chronic damages make it harder for skin to reach optimal integrity and function. The first step in the natural process of healing includes the inflammation stage, which includes blood clot formation and vasoconstriction. These events help prevent blood loss and any further infections. Following this is the re-epithelization process, which replaces the epithelium. Keratinocytes are the major cells involved in this procedure as they migrate to the site of the wound and kickstart the process. However, if this does not happen, then the wound fails to heal completely and is open to the risk of being damaged again. This cannot be controlled and can have repercussions, making it important to have therapies that can overcome these natural limitations.

Basics of stem cells

Definition of stem cells and their unique properties 

Stem cells differentiate into various specialized cell types and perpetually self-renew (the new stem cells are completely identical to the originating cell). These two characteristics make them ideal for use in medical therapies, especially when cells need to be repaired and replaced.

Types of stem cells

There are several types of stem cells as shown in the table below.

Type of cellCharacteristics
EmbryonicEmbryonic stem cells are derived from the inner cells of a blastocyst and have the potential to divide into many types of cells.
Adult (somatic)These are generally found in specific locations to compensate for normal wear or tear of tissues. They begin to divide only when they are activated.
Induced pluripotent stem cells (iPSC)This involves reprogramming mature adult cells into embryonic stem cells-like states. This gives them the ability to form into 3 different types of cells.

Stem cells in cutaneous repair

Sources of stem cells for cutaneous repair

      1. Epidermal stem cells (ESC)

Epidermal stem cells are multipotent in nature and can be found in a microenvironment called ‘niche’. These can easily accessed and be used in cutaneous repair by preparing a stable keratinocyte layer after an injury. They have been used with fibroblasts and a plasma matrix to restore dermal and epidermal components.

      2. Mesenchymal stem cells (MSC)

Mesenchymal stem cells are stromal cells that are easier to extract from various parts of the body (eg: adipose tissue, menstrual blood, bone marrow and more). They are generally mobilised during needs for repair and regeneration. Since they have more limitations as compared to epidermal stem cells, they need to be treated with biological and pharmacological agents before implantation. This helps with the conditioning of the cells to reach optimal therapeutic potential in terms of cutaneous repair. 

      3. Adipose-derived stem cells (ASC)

Adipose-derived stem cells are mesenchymal stem cells that can be extracted with a minimally invasive method. They tend to react more effectively to growth factors making them useful in carrying out cutaneous repair. ASCs can be derived from either brown or white adipose tissue but most research is carried out on these cells extracted from white adipose tissue.

Preclinical and clinical studies demonstrating the effectiveness of stem cells in treating cutaneous injuries

Since this field is highly dynamic, it is necessary to consult various medical professionals before undergoing any treatment for cutaneous repairs. In terms of pre-clinical studies, animal models are a common way of figuring out the effectiveness of certain stem-cell therapies. This involves attempting to cure skin damage by applying stem cells to mice with cutaneous damage. Another form is through research on collagen production by stem cells, which are necessary for normal skin repair.

Clinical methods, however, vary in terms of the realistic consequences of a therapy. Clinical trials have been carried out on patients with burn injuries as well as chronic ulcers. In such situations, stem cell therapies have been proven to accelerate wound healing and minimise the effects of scarring on cutaneous tissue. By seeking results for these conditions, stem cells are now being applied to scar reduction cosmetic treatments as well as skin disorders like vitiligo. 

Mechanisms of action

Explanation of how stem cells contribute to cutaneous repair

Stem cells can differentiate and regenerate tissue aiding in cutaneous repair. Additionally, they are migratory in nature making them effective in repairing damaged skin. There’s a series of cells they need to replace, including hair follicle cells, blood vessels, epidermal cells, etc.

Cell growth and angiogenesis

Cell growth is stimulated by growth factors and other bioagents which allow stem cells to differentiate into various cell types. Hair follicle cells can differentiate further into sebaceous glands and epidermal cells when needed. This makes the process of cutaneous repair more efficient. 

Angiogenesis is the formation of blood vessels. This is usually done by the mesenchymal stem cells. Subsequently, this provides the remaining stem cells with enough oxygen and nutrients to proliferate and repair the damaged regions of the skin tissue.

Immune response and wound healing 

Stem cells have immunomodulatory properties that regulate the immune response, such as inflammation in the wounded region. MSCs produce prostaglandin, which activates the release of anti-inflammatory molecules. It also promotes angiogenesis, therefore making scarless repair a possibility.

Challenges and considerations

Ethical concerns related to embryonic stem cell use

Embryonic stem cells are extracted from the early stages of a blastocyst and have the capability of transforming into many different cell types. However, there is an ethical dilemma with using these cells. Some believe that the destruction of an embryo by the removal of these cells is equivalent to destroying life, whereas others believe that an embryo is not developed, so it can be considered ethical. Due to this controversy, some countries have banned embryonic stem cell research.

Risk of tumour formation 

The use of stem cells for cutaneous repair is useful in restoring the functionality and strength of the skin. However, such therapies also bear a high risk of tumour formation. As stem cells can divide endlessly, there could be an accumulation of mutation within the divisions. This could result in the formation of teratomas (tumours). 

Immune rejection of transplanted stem cells

ESCs are prone to rejection as compared to iPSCs making these a better choice for skin grafts. By extracting the cells from patients themselves, we can reduce the chances of immune rejection.

Future prospects and innovations

Tissue engineering and 3D bioprinting

Tissue engineering is the process of using cells and scaffolds. It can be used to maintain or restore damaged tissues and organs. The scaffolding helps provide cells with an environment of growth factors and signalling molecules that can aid in the growth of a specific tissue for repair. Recent advances in this area of research have seen the growth of lung, skin and kidney tissues in the lab. Although some of these have been implemented in patients, there’s still a long way to go in minimising costs and increasing the suitability of the tissues and organs created.

3D bioprinting involves the use of 3D printers with bio-inks (cells, biomaterials and factors) that are constructed in a layered manner to replicate skin in terms of cutaneous repair. For skin-related bioprinting, excursion technology and inkjet printing are widely used. Excursion technology is the use of pneumatic pressure to squeeze out biomaterials through a nozzle, whereas inkjet technology uses thermal effects to generate bubbles that exude bio-ink on demand. 

The use of these two methods is still being perfected to gain an easier and cheaper method of making skin for patients.

Personalized medicine and patient-specific stem cell therapies

Personalized medicine is a novel field that caters to each patient based on their condition. Since it is specific to each individual’s body and condition, it eliminates the need to undergo many therapies to find one that has optimal results. Personalised medicine also involves the use of molecular diagnostics, which help predict the way the patient will respond to a certain treatment. This also takes into account other factors like the growth environment of the cells, their origin and placement for repair. Through this, personalised therapies can be evaluated to optimise the efficient mode of treatment.

Ongoing research and potential breakthroughs in enhancing cutaneous repair

Apart from stem cell therapies, there are other avenues that scientists are researching to improve wound healing. One such method is the use of nanoparticles to release therapeutic agents directly into the skin at the site of repair making healing a faster process. Some researchers are also working on producing immunomodulatory molecules that can be used alongside stem cells to produce scarless sites.

Summary

Stem cells have a lot of potential in cutaneous repairs. With emerging ways to inculcate stem cells into therapies, it is important to consider their effectiveness in wound healing, especially for regions like the skin where most people prefer quick and clean healing. Since stem cells can be extracted from many sources, they make for a good solution to skin conditions and have a wide range applications.

Stem cell therapies are currently expensive due to the novelty of the technology; however, with increasing funding and advancements in technology, costs can be reduced, making stem cell therapies accessible to all with skin conditions. Another barrier with stem cells includes approval, as not all countries are supportive of stem cell research and applications. By getting over this and globally collaborating, stem cell therapies could become the future of scarless wound healing.

References

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Soumya Iyer

International Baccalaureate, Natural Sciences, Global Schools Foundation

Soumya is currently an undergraduate student pursuing BSc Biological and Biomedical Sciences (joint degree with National University of Singapore) at the University of Dundee, Scotland. As someone very passionate about scientific communication, she’s undertaken this internship following her previous experience in writing scientific reports.

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