STEM CELL THERAPY. Dr.MANOJ

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1 STEM CELL THERAPY Dr.MANOJ

2 Stem cell treatments are a type of intervention strategy that introduces new adult stem cells into damaged tissue in order to treat disease or injury The ability of Stem Cells to self renew offers significant potential for generation of tissues that can potentially replace diseased and damaged areas in the body, with minimal risk of rejection and side effects.

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4 Medical researchers anticipate that adult and embryonic stem cells will soon be able to treat Cancer, Type 1 Diabetes Mellitus, Parkinson s disease, Huntington's disease, Celiac Disease, Cardiac Failure, Muscle Damage and Neurological Disorders.

5 Current Treatments Hematopoietic stem cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood. Traditionally these procedures have been reserved for patients with life threatening diseases.

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7 Indications Multiple Myeloma Leukemia Pediatric cases where the patient has an inborn defect such as severe combined immunodeficiency or congenital neutropenia Aplastic Anemia Sickle cell disease, Neuroblastoma, Lymphoma, Ewing's Sarcoma, Desmoplastic small round cell tumor, Chronic Granulomatous disease and Hodgkin's disease.

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9 Sources of Stem Cells Bone Marrow Peripheral blood stem cells Amniotic Fluid Umbilical Cord Blood

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11 Graft Types Autologous HSCT It requires the extraction of haematopoietic stem cells (HSC) from the patient and storage of the harvested cells in a freezer. The patient is then treated with high dose chemotherapy with or without radiotherapy with the intention of eradicating the patient's malignant cell population at the cost of partial or complete bone marrow ablation The patient's own stored stem cells are then returned to his/her body, where they replace destroyed tissue and resume the patient's normal blood cell production. Advantages: Lower risk of infection during the immune compromised portion of the treatment. Patients experiencing rejection (graft versus host disease) is very rare due to the donor and recipient being the same individual.

12 Allogeneic HSCT Graft Types Involves two people: the (healthy) donor and the (patient) recipient. Allogeneic HSC donors must have a tissue Human Leukocyte Antigen (HLA) type that matches the recipient. Even if there is a good match at these critical alleles, the recipient will require immunosuppressive medications to mitigate graftversus host disease. Allogeneic transplant donors may be related (usually a HLA matched sibling), syngeneic (a monozygotic or 'identical' twin of the patient necessarily extremely rare since few patients have an identical twin, but offering a source of perfectly HLA matched stem cells) or unrelated (donor who is not related and found to have very close degree of HLA matching). Allogeneic transplants are also performed using umbilical cord blood as the source of stem cells.

13 Complications Infection: Bone marrow transplantation usually requires that the recipient's own bone marrow be destroyed Myeloablation" Prior to "engraftment" patients may go for several weeks without appreciable numbers of white blood cells to help fight infection. This puts a patient at high risk of infections, sepsis and septic shock, despite prophylactic antibiotics. However, antiviral medications, such as Acyclovir and Valacyclovir, are quite effective in prevention of HSCT related outbreak of herpetic infection in seropositive patients. The immunosuppressive agents employed in Allogeneic transplants for the prevention or Treatment of graft versus host disease further increase the risk of opportunistic infection. Immunosuppressive drugs are given for a minimum of 6 months after a transplantation, Transplant patients lose their acquired immunity, for example immunity to childhood diseases such as measles or polio. For this reason transplant patients must be re vaccinated with childhood vaccines once they are off immunosuppressive medications.

14 Complications Veno Occlusive Disease: Severe liver injury can result from hepatic venoocclusive disease (VOD) clinically seen as Elevated levels of bilirubin, hepatomegaly and fluid retention. Severe cases of Sinusoidal Obstruction Syndrome are associated with a high mortality rate. Anticoagulants or defibrotide may be effective in reducing the severity of VOD but may also increase bleeding complications.

15 Complications Mucositis: The injury of the mucosal lining of the mouth and throat is a common regimen related toxicity following ablative HSCT regimens. It is very painful, and prevents eating and drinking. Mucositis is treated with pain medications plus intravenous infusions to prevent dehydration and malnutrition.

16 Complications Graft Vs. Host Disease It is an inflammatory disease that is unique to allogeneic transplantation. It is an attack of the "new" bone marrow's immune cells against the recipient's tissues. This can occur even if the donor and recipient are HLA identical because the immune system can still recognize other differences between their tissues. Because bone marrow transplantation is the only transplant procedure in which the transplanted cells must accept the body rather than the body accepting the new cells. Acute: Typically occurs in the first 3 months after transplantation and may involve the skin, intestine, or the liver.. High dose corticosteroids such as prednisone are a standard treatment Chronic: In addition to inflammation, chronic graft versus host disease may lead to the development of fibrosis, or scar tissue, similar to scleroderma. It may cause functional disability and require prolonged immunosuppressive therapy.

17 Complications Graft Vs. Tumor Effect: It is due to a therapeutic immune reaction of the grafted donor T lymphocytes against the diseased bone marrow of the recipient. Graft versus tumor effect (GVT) or "graft versus leukemia" effect is the beneficial aspect of the Graft versus Host phenomenon. This Graft versus tumor is mainly beneficial in diseases with slow progress, e.g. chronic leukemia, low grade lymphoma, and some cases multiple myeloma. If cancer relapses after HSCT, another transplant can be performed, infusing the patient with a greater quantity of donor white blood cells.

18 Prognosis for HCST It varies widely dependent upon disease type, stage, stem cell source, HLA matched status (for allogeneic HCST) and conditioning regimen. A transplant offers a chance for cure or long term remission if the inherent complications of graft versus host disease, immuno suppressive treatments and the spectrum of opportunistic infections can be survived. In recent years, survival rates have been gradually improving across almost all populations and subpopulations receiving transplants.

19 Potential Treatments Brain Damage: Stroke and traumatic brain injury lead to cell death, characterized by a loss of neurons and oligodendrocytes within the brain. Healthy adult brains contain neural stem cells which divide to maintain general stem cell numbers, or become progenitor cells. Stem cells may also be used to treat brain degeneration, such as in Parkinson's and Alzheimer's disease.

20 Potential Treatments Cancer: Stem cell therapies may serve as potential treatments for cancer as current cancer treatments are designed to kill cancer cells however The stem cells neither differentiated nor turned tumorigenic. Essentially, chemotherapy is used to completely destroy the patients own lymphocytes, and stem cells injected, eventually replacing the immune system of the patient with that of the healthy donor.

21 Conventional Vs. Stem Cell Therapy for Cancer

22 Potential Treatments Spinal Cord Injury: Multipotent isolated adult stem cells from umbilical cord blood were injected into the damaged part of the spinal cord of a patient suffering from a spinal cord injury and following the procedure, she could walk on her own, without difficulty. The observed recovery was associated with differentiation of transplanted cells into new neurons and oligodendrocytes the latter of which forms the myelin sheath around axons of the central nervous system, thus insulating neural impulses and facilitating communication with the brain.

23 Potential Treatments Heart Damage: Several clinical trials targeting heart disease have shown that adult stem cell therapy is safe, effective, and equally efficient in treating old and recent infarcts Stem cell therapy for treatment of myocardial infarction usually makes use of autologous bone marrow stem cells Possible mechanisms of recovery include: Generation of heart muscle cells Stimulation of growth of new blood vessels to repopulate damaged heart tissue Secretion of growth factors

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26 Potential Treatments Haematopoiesis: The immune system is vulnerable to degradation upon the pathogenesis of disease, and because of the critical role that it plays in overall defense, its degradation is often fatal to the organism. Fully mature human red blood cells may be generated ex vivo by hematopoietic stem cells (HSCs), which are precursors of red blood cells. In this process, HSCs are grown together with stromal cells, creating an environment that mimics the conditions of bone marrow, the natural site of red blood cell growth.

27 Potential Treatments Baldness: Act by activating already existing stem cells on the scalp. Later treatments may be able to simply signal follicle stem cells to give off chemical signals to nearby follicle cells which have shrunk during the aging process, which in turn respond to these signals by regenerating and once again making healthy hair.

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29 Potential Treatments Missing teeth: Stem cells taken from the patient could be coaxed in the lab into turning into a tooth bud which, when implanted in the gums, will give rise to a new tooth, and would be expected to grow within two months. It will fuse with the jawbone and release chemicals that encourage nerves and blood vessels to connect with it.

30 Potential Treatments Deafness: Success case reports by re growing cochlea hair cells with the use of embryonic stem cells to correct deafness. Blindness and Vision impairment: Sheets of retinal cells used are harvested from aborted fetuses. When these sheets are transplanted over the damaged cornea, the stem cells stimulate renewed repair, eventually restore vision. The first successful human transplant was a cornea transplant. The absence of blood vessels within the cornea makes this area a relatively easy target for transplantation. The majority of corneal transplants carried out today are due to a degenerative disease called keratoconus.

31 Potential Treatments Diabetes: Diabetes patients lose the function of insulin producing beta cells within the pancreas. Human embryonic stem cells may be grown in cell culture and stimulated to form insulin producing cells that can be transplanted into the patient. However, clinical success is highly dependent on the development of the following procedures: Transplanted cells should proliferate Transplanted cells should differentiate in a site specific manner Transplanted cells should survive in the recipient (prevention of transplant rejection) Transplanted cells should integrate within the targeted tissue Transplanted cells should integrate into the host circuitry and restore function

32 Potential Treatments Orthopaedics: The focus in the literature for musculoskeletal care appears to be on mesenchymal stem cells. A published safety study conducted in a group of 227 patients over a 3 4 year period shows adequate safety and minimal complications associated with mesenchymal cell transplantation.

33 Potential Treatments Wound healing: Stem cells can also be used to stimulate the growth of human tissues. In an adult, wounded tissue is most often replaced by scar tissue, which is characterized in the skin by disorganized collagen structure, loss of hair follicles and irregular vascular structure. In the case of wounded fetal tissue, however, wounded tissue is replaced with normal tissue through the activity of stem cells. A possible method for tissue regeneration in adults is to place adult stem cell "seeds" inside a tissue bed "soil" in a wound bed and allow the stem cells to stimulate differentiation in the tissue bed cells. This method elicits a regenerative response more similar to fetal wound healing than adult scar tissue formation. Researchers are still investigating different aspects of the "soil" tissue that are conducive to regeneration.

34 Potential Treatments Infertility: Culture of human embryonic stem cells in mitotically inactivated porcine ovarian fibroblasts (POF) causes differentiation into germ cells (precursor cells of oocytes and spermatozoa), as evidenced by gene expression analysis. Human embryonic stem cells have been stimulated to form Spermatozoon like cells, yet still slightly damaged or malformed. It could potentially treat azoospermia.

35 Potential Treatments Cosmetic Surgery : Stem cell rich fat can be used to enhance and treat the eyes, forehead, temples, cheeks, laugh lines, frown lines, jowls, jaw line, chin, hands, buttocks, labia majora, calves, cellulite dimples and scar reduction. Adult stem cells, which are derived from the fat, are able to differentiate and become unique tissue types including: fat, bone, muscle, cartilage and nerve covering. They are activated when there is an inflammatory response to an injury or procedure Adult stem cells will divide and grow; they then take the form of the surrounding tissue.

36 Advantages to stem cell enhanced reconstruction over the older methods: May be done under local anesthesia No cutting or stitches Your own natural fat and stem cells Minimal risk of complications Minimal recovery time Natural looking results Helps to correct defect by filling and restoring symmetry Helps improve appearance of skin Regenerates and heals tissues Improves blood flow to the area Softens scars Long lasting results No foreign materials At a fraction of the cost of older methods

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38 Thank You