stem cell therapy in dermatology final-61.pptx

Stem cell therapy in dermatology covers the domains where it can be used as an effective treatment

1. STEM CELL THERAPY IN DERMATOLOGY DR JAVERIA BUSHRA TOUQIR RESIDENT DERMATOLOGIST

2. Stem cells are undifferentiated cells present in different organ systems with the three hallmark characteristics of self-renewal, differentiation and plasticity

3. PROPERTIES OF STEM CELLS Property Definition Self-renewal Ability to undergo numerous cycles of asymmetrical cell division to produce differentiated cells as well as cells that are similar to the parent cell, thereby maintaining the pool of undifferentiated cells Differentiation Ability to differentiate into cells of the tissue in which stem cell is located Plasticity/trans-differentiation Ability of adult stem cells to cross lineage barriers and differentiate into cells of tissue different from the original tissue

4. FIRST SUCCESSFUL BMT Dave Stahl was the recipient of the world's first successful bone marrow transplant to treat Burkitt's lymphoma - a rare and aggressive form of cancer. He was 16 years old when he received his transplant in 1975

5. WHAT DISEASES CAN BE CURED BY STEM CELLS Any disease where there is possible tissue destruction can be cured with stem cells Alzheimer’s disease Parkinson’s disease Spinal cord injury Heart diseases Severe burns Diabetes

6. CLASSIFICATION OF STEM CELLS

7. Classification on the basis of differentiating capacity Totipotent or omnipotent The ability to differentiate into all possible cell types including placenta Cells produced by the first few divisions of the fertilized egg, known as morula cells, are totipotent Pluripotent The ability of a stem cell to turn into all mature cell types of the body of all the three germ layers, except placenta Embryonic stem cells that are isolated from an early stage embryo, called blastocyst are pluripotent cells Multipotent The ability to turn into more than one mature cell type of the body, usually a restricted and related group of different cell types Oligopotent The ability to differentiate into a few cells. Example: Adult lymphoid or myeloid stem cells. Unipotent Can produce only one cell type Muscle stem cells

8. Classification on the basis of their source Embryonic stem cell Pluripotent stem cells present in the inner cell mass of blastocyst which are capable of producing all organs in human body except for placenta Somatic/adult stem cell Somatic stem cells (multipotent or unipotent), with limited plasticity, present in many tissues including skin and bone marrow iPSC Recently, the induced pleuripotent stem cells have emerged as a distinct variety.

9. EPIDERMAL STEM CELLS In skin, stem cells are found in inter-follicular epidermis (keratinocyte), bulge of the hair follicle (keratinocyte, melanocyte and neuronal) sebaceous gland dermal papillae, dermis subcutaneous tissue (mesenchymal ).

10. BONE MARROW STEM CELLS Bone marrow contains:

11. HEMATOPOIETIC STEM CELLS derived from bone marrow and umbilical cord blood used in autoimmune disorders can be autologous or allogeneic

12. Mesenchymal stem cells : derived from almost all tissues low immunogenicity by virtue of their low MHC expression immunomodulatory effects utility in many diseases including inflammatory diseases relatively easy tissue isolation capacity of migrating and homing to the injured site (e.g., tumor tropism) ability to expand for a relatively long period of time

13. DERMATOLOGICAL CONDITIONS IN WHICH STEM CELLS HAVE BEEN TRIED Good results Promising results Results with low evidence Discouraging results Systemic sclerosis SLE Pemphigus Psoriasis Vitiligo Wound healing Scleromyxedema Alopecia HIV Melanoma Aesthetic medicine Epidermolysis bullosa Merkel cell carcinoma

14. STEM CELL THERAPY IN PEMPHIGUS VULGARIS The proposed mechanism of action is that the transplanted stem cells repopulate the immune system, the number of autoreactive immune cells decline and this helps to restore the immunological balance.

15. A 26-year-old lady suffering from pemphigus vulgaris with pruritic blisters seen on face and neck: (a) status before HSCT; (b) 3 years after HSCT. A prospective clinical trial of hematopoietic stem cell transplantation (HSCT) in thymus, bone marrow (BM) and periphery was carried out to reconstitute central and peripheral arms of self-tolerance

16. (a) Suprabasal bullous cavity of pemphigus vulgaris with few acantholytic cells (Hematoxylin and Eosin stain, ×40) before HSCT; (b) indirect immunofluorescence stain showing linear IgG deposits on basal layer of bullous cavity Completely recovered skin after HSCT, showing unremarkable epidermis, dermis and underlying connective tissue (Hematoxylin and Eosin stain, ×40); (b) negative immunofluorescence with anti-human IgG

17. STEM CELL THERAPY IN SYSTEMIC SCLEROSIS First autoimmune diseases to be subjected to stem cell therapy. Suitable candidates include: Patients with acute onset rapidly progressive disease refractory to conventional therapy mild initial organ damage

18. CASE SCENARIO A young female with systemic sclerosis and acute occlusive ischemia presented with gangrene of upper and lower limbs After IV infusion of autologous bone marrow –derived mesenchymal stem cells, skin necrosis decreased . Post infusion angiography showed new vessel network in both upper and lower limbs

19. How does it works By differentiating into endothelial cells, mesenchymal stem cells may help form new vessels A promising therapy indeed

20. Autologous hematopoietic stem cell therapy

21. STEM CELL THERAPY IN SYSTEMIC LUPUS ERYTHEMATOUSES

22. A case of severe plaque psoriasis successfully treated with allogeneic gingiva-derived MSCs STEM CELL THERAPY IN PSORIASIS

23. The effects of G-MSC infusions on a 19-year-old man with a 5-year history of severe plaque psoriasis. (a) Baseline/ preinfusion images showing demarcated, round, erythematous plaques on upper chest and abdomen. (b) Gradual clearing of plaques after two successive weekly administrations of MSCs. (c) Lesions fully cleared after three more MSC infusions. The patient has been free of psoriasis for 3 years now

24. STEM CELL THERAPY IN EPIDERMOLYSIS BULLOSA mesenchymal stem cells from the donor can be introduced intradermally or intravenously, bone marrow transplant can be done from allogeneic donor patient’s stem cells can be genetically modified and transplanted While hematopoietic stem cell therapy has failed to live up to its initial promise, allogenic mesenchymal stem cells therapy may be useful in alleviating some symptoms

25. Generalized recessive dystrophic epidermolysis bullosa (EB)

26. Treatment effect of intravenous allogeneic bone-marrow derived mesenchymal stem cells infusion in RDEB. The upper back of a 26-year-old patient with severe RDEB demonstrates improved wound healing and less inflammation 100 days after intravenous allogeneic mesenchymal stem cells infusion.

27. CASE SENARIO A 7-year-old patient with generalized junctional epidermolysis bullosa , non- Herlitz type, presented in July of 2015. Since birth, the patient had suffered from blistering o f the entire body with particular manifestations in the extremities, back and flanks. The patient was admitted to the burn unit due to an acute exacerbation and risk of sepsis. At the time of admission, approximately 60% of his total body surface area was affected by epidermal destruction and also showed bacterial infection with Staphylococcus aureus and Pseudomonas aeruginosa. During the hospitalization, the patient’s condition deteriorated severely resulting in a complete epidermal loss of 80% of the body surface area.

28. The plan was to obtain epidermis with highly potent epidermal stem cells from a small skin biopsy and transfect the cells by retroviral gene transfer of the intact LAMB3 sequence . Subsequently, expansion of transfected cells was done to create keratinocyte grafts with intact transfected epidermal stem cells for transplantation . These grafts were intended to cover the entire area of epidermal loss in a multi-step transplantation procedure. In February 2016, the patient could be discharged with a completely regenerated transgenic epidermis in the transplanted areas.

29. Immunofluorescence analysis demonstrated that the amount of the dermo-epidermal structural protein laminin-332, was equivalent to that of healthy skin

30. STEM CELL THERAPY IN WOUND HEALING Epidermal stem cells have the potential to regenerate the epidermis and differentiate into various cell types and tissue Mesenchymal stem cells have been shown to promote wound healing by decreasing inflammation, promoting angiogenesis and decreasing scarring

31. STEM CELL THERAPY IN VITILIGO Best results in Focal Segmental Localized Isolated On legs, feet, face & forearm

32. TECHNIQUES NCES ( NON CULTURED EPIDERMAL STEM CELLS) Dermabrader to scrape white skin patch Sprayed them with skin cells including melanocytes Repigmentation in 68% population NCORSHFS (AUTOLOGOUS NONCULTURED OUTER ROOT SHEET HAIR FOLLICLE CELL SUSPENSION) Digesting hair follicle with trypsin EDTA Equally effective as NCES

33. ( a) Segmental vitiligo of the face before melanocyte transplantation, (b) Repigmentation 6 months after melanocyte transplantation (good cosmetic result)

34. A patient with segmental vitiligo on the right arm; (b) Repigmentation after non-cultured cellular grafting 

35. STEM CELL THERAPY IN ALOPECIA Promising results in both androgenetic alopecia (AGA ) and alopecia areata (AA) PROCEDURE: Autologous adipose-derived stromal vascular cells isolated through lipoaspiration and injected into the scalp of 20 patients At three and six months of follow-up, they found statistically significant hair growth in all the patients.

36. Representative photographs of the AGA improvement after SVF treatment. Baseline (pre-injection) versus 6 months (post-injection) global photographs after treatment

37. STEM CELL THERAPY IN MERKEL CELL CARCINOMA Polychemotherapy with Autologous peripheral blood stem cell transplantation resulted in remission, though it lasted only six months

38. Step 1: Blood is taken from a vein in the patient’s arm and flows through an apheresis machine that removes the stem cells. The remaining blood is returned to a vein in the other arm. Step 2 : The patient receives chemotherapy to kill cancer cells. Healthy cells, including blood-forming cells, are also destroyed by the cancer treatment . Step 3 : After the patient completes chemotherapy or radiation therapy (not shown), the stem cells are given back to the patient to replace the blood-forming cells that were destroyed by the cancer treatment. The stem cells help the bone marrow recover and make healthy blood cells .

39. STEM CELL THERAPY IN ASTHETIC MEDICINE

40. STEM CELLS FOR FACE LIFTING Non-surgical facelift   is a three-step facial rejuvenation process. F irst step fat extraction through liposuction added benefit of contouring other parts of the body. S econd step harvested fat is purified down to the stem cells T hird step injection—where these refined cells will be inserted into the surgical site to improve your appearance and recovery.

41. STEM CELL ETHICS

42. THE ETHICAL DEBATE In favor of ESCR ESCR fulfills the ethical obligation to alleviate human suffering Since excess IVF embryos will be discarded anyway, isn’t it better that they be used in valuable research Therapeutic cloning produces cell in petri dishes not in pregnancy

43. DIFFICULTIES IN STEM CELL THERAPY Ethical considerations
Legal issues: The limitation is that, currently, the best available is only guidelines not laws
Possibility of graft rejection in allografting.
Tumorigenicity of pluripotent stem cells
Future research regarding ideal patient selection, timing of intervention, appropriate conditioning regimens, post-intervention care and cost effectiveness would help to optimize the results of stem cell therapy.