Cell Therapy in Dermatology

Introduction:

Stem cells may be used to treat various disorders, especially in which conventional methods do not yield promising results. It is a novel treatment modality that is fast evolving and an area in which extensive research is being conducted. Stem cell research has new frontiers in the field of dermatology. It is a revolutionary modality that has the potential to treat chronic as well as acute skin conditions.

What Is the Need for Cell Therapy in Dermatology?

Skin is the primary protective barrier for the body. But most skin conditions affect this property of the skin. There could be disruption in skin barrier function by biological, genetic factors, or infections. Most genetic disorders are characterized by the loss of continuity of the skin. This can lead to loss of water and electrolytes, infections, systemic conditions, and impaired thermoregulation. In addition, genetic conditions can alter the molecular structure of the skin, leading to blisters, erosions, or other lesions.

Skin problems can also be a result of burns, mechanical trauma, or the adverse effects of medication. It can also be a result of systemic disorders such as diabetes mellitus, neuropathies, hypertension, autoimmunity, and vascular problems. Conventional treatment is mainly symptom-related and depends on corticosteroids for autoimmune disorders. The goal of treatment is to re-establish the integrity of skin that has been lost. Novel research in stem cell therapy has helped to use it for restoring the epithelium and healing skin function. If used properly, it has the potential to treat skin conditions without the adverse effects that other medications may cause.

What Are Stem Cells?

Normally a cell would mature and have a specific function. Stem cells are those that are not differentiated for a particular function. They have the potential to differentiate into specialized cells under certain conditions. This ability of stem cells to modify to perform the desired function is utilized in cell therapy. It can replace faulty cells or non-functional cells. This is the ideology behind stem cell therapy.

Stem cells are broadly classified into:

• Embryonic.

• Adults.

They can be isolated from:

• Bone marrow.

• Umbilical cord.

• Adipose tissue.

How Does Stem Cell Work?

Stem cell that is not yet differentiated has three characteristics:

• Self-Renewal: It is the ability to multiply and produce differentiated cells as well as cells similar to parent cells.

• Differentiation: Ability to differentiate to cells of tissue in which the stem cells are located.

• Plasticity: The ability to transform or trans-differentiate. That is, it can modify cells that are different from the original tissue.

Stems cells may be classified based on their capability to differentiate:

• Omnipotent or Totipotent: It can differentiate into all possible cell types.

• Fertilized Egg: Cells that are produced in the initial divisions of a fertilized egg.

• Pluripotent: It can differentiate into cells of all three germ layers.

• Multipotent: It can differentiate into more than one mature cell type of the body. For example, hematopoietic cells can be white blood cells, red blood cells, or platelets.

Mesenchymal stem cells can become bone, connective tissue, cartilage, or adipose tissue.

• Oligopotent: Ability to differentiate into a few cells. Example: Myeloid stem cells.

• Unipotent Cells: They can only produce one type of cell. Example: Muscle stem cells.

Stem cells are present in a microenvironment called the stem cell niche. It functions as a group to maintain homeostasis and repair tissues at the time of injury.

What Is Stem Cell Therapy?

This potential of stem cells to differentiate and regenerate is utilized in stem cell therapy.

In the case of skin conditions, keratinocytes and fibroblasts from human skin have been found to have the ability to be used in cell therapy. Patients with hereditary or acquired skin conditions who have defective skin have been treated with cultured stem cells and bioengineered skin products. Cells from sites other than skin, such as bone marrow, are under research. The plasticity ability can be harnessed in regenerating skin.

Epidermal Stem Cells:

In the skin, stem cells may be found in :

• Bulge of the hair follicle - Melanocyte, neuronal, keratinocyte.

• Interfollicular epidermis - Keratinocyte.

• Sebaceous gland.

• Dermis.

• Subcutaneous tissue - Mesenchymal.

• Dermal papillae.

Melanocytes can be activated by ultraviolet light using laser, radiation, and drugs such as Tacrolimus. This property can be used for vitiligo. Under normal conditions, stem cells from the epidermis, hair follicles, and sebaceous glands differentiate independently. But in the case of an injury, because of plasticity (ability to trans-differentiate), any stem cell can produce other mature cells.

What Are the Uses of Stem Cells in Dermatology?

Stem cells may be used to treat various disorders, such as:

1. Pemphigus:

Corticosteroids and immunosuppressants are considered to be the first line of treatment. This is because pemphigus is an autoimmune disorder where the body's antibodies attack itself. In cell therapy, stem cells are used to repopulate the immune system, and this causes the autoimmune cells to decline and thereby helps immunological balance.

2. Systemic Sclerosis:

This, too, is an autoimmune disorder. Since a definite treatment is still unavailable, this disease is among the first to be treated with stem cell therapy. Hematopoietic stem cell therapy is used to ablate self-reactive T and B cells. The immune system is renewed by infusing patients with already collected hematopoietic stem cells. Patients with acute onset have a better prognosis than a long-standing disease. Patients with long-standing diseases and organ damage are contraindicated from undergoing this therapy.

3. Psoriasis:

It is another disease that has been tested with stem cell therapy. The idea was initiated after noticing that psoriasis patients undergoing stem cell therapy had remission from the disease. Ironically, patients who have received bone marrow transplants from donors with psoriasis have contracted the disease.

4. Systemic Lupus Erythematosus:

Mesenchymal stem cells have been found safe and effective in SLE. It has shown a decrease in disease activity, a reduction in the production of autoantibody, and an improvement in renal function. The ability of cell therapy in immunomodulation and regeneration makes them useful in treating SLE.

5. Epidermolysis Bullosa:

This is an inherited disorder in which minor trauma can lead to blisters. It is a condition in which no specific treatment has been found to date. The skin is extremely fragile and characterized by delayed wound healing, erosions, and scarring. Stem cell therapy is one of the many modalities that has been used to correct the genetic defect, thereby restoring the skin barrier. Mesenchymal stem cells may be introduced through veins (intravenously) or the skin (intradermally). Bone marrow transplantation can be done from a donor with a matching genetic constitution, or the patient's stem cells may be modified and transplanted. Fibroblasts may be isolated and cultured to help increase the cell-to-cell adhesion.

6. Wound Healing:

Epidermal cells have the potential to regenerate and differentiate at appropriate times. This can be made useful in treating non-healing wounds. Mesenchymal cells can promote wound healing by decreasing inflammation and also help to reduce scarring.

7. Vitiligo:

Medical treatment is the first line of treatment; in non-responsive cases, surgical therapies may be considered. These include grafts, both tissue and cellular. The melanocytes on the hair follicle have remarkable regenerative properties and can act as a source of melanocytes and can be used to treat vitiligo.

8. Alopecia:

Stem cell therapy is useful in treating both androgenic alopecia and alopecia areata. Stem cells can be used for hair restoration.

9. Melanoma:

It is an aggressive tumor that is non-responsive to radiotherapy and chemotherapy. Even immunotherapy and oncogene-directed therapy have poor results. Tumor cells can proliferate and cause relapse. So the treatment is targeted at these cells.

10. Aesthetic Medicine:

Stem cells derived from adipose tissue have the potential to activate fibroblasts, secrete growth factors, and thereby antioxidants, lightening pigmentation, and wound healing. They are also found to help treat wrinkles in animals. Fibroblasts can restore dermal properties that have been lost. All these can be useful in aesthetic medicine.

11. Keratinocytes and Skin Grafting:

It has been found that keratinocytes can be cultured and used for grafting. Sheets of the epithelium may be cultured from a small piece of skin.

12. Bone Marrow Cells and Skin:

Bone marrow cells can differentiate into mesodermal, ectodermal, and endodermal cells. It can also differentiate into keratinocytes, which can be further used in treating skin conditions.

What Are the Difficulties in Stem Cell Therapy?

• Legal Issues: Proper legal framework has been established so that there is no unethical and unscientific use of stem cell therapy. Rules have to be formulated in the research field as well as treatment areas.

• Ethical Considerations: Consent has to be issued, confidentiality has to be maintained, and donor cells have to be screened for diseases that could be transmitted.

• Graft rejection.

• Stem cell preservation is still an area to be explored. There are limitations in storing and preserving the viability of stem cells.

• Tumorigenicity: Stem cells can self-renew and multiply, which can lead to undesirable mutations and may differentiate into tumors.

• Selection of Patients: In some diseases, since the treatment success depends on the patient, time-elapsed since the onset, proper screening, and selection of patients greatly determine the outcome.

• It is difficult to ensure that stem cells differentiate into the desired function.

• Biomarkers are necessary to ensure cellular purity.

• The mode of delivery or grafting is to be selected carefully.

• These cells may cause an immune response in the patient. Hence proper monitoring is necessary.

• The cost-risk ratio should be properly assessed before a patient is subjected to cell therapy.

• Another hurdle in cell therapy is that ethnic differences should be considered, especially in dermatological conditions. The outcome of the treatment relies on this.

Conclusion:

Stem cell therapy is a revolutionary treatment modality that has the potential to treat many diseases. The ability of skin cells to transform can be used to treat many skin conditions. It is also a good alternative to immunosuppressive agents that are usually used for autoimmune disorders. In addition, it can treat chronic wounds, ulcers, and hereditary diseases. Coupled with bioengineering technologies, these modalities can give promising results.