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STEM CELL THERAPY

Presented by Mrs. S.Jeyalakshmi, M Sc (N), Asst. Professor


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STEM CELLS
Stem cells are the bodys master cells Primitive cells Stem cells has the ability to renew themselves through mitotic cell division and differentiating into a diverse range of specialized cell types.

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STEM CELLS
Rare Stem cells that are found in bone marrow, peripheral blood, and cord blood are called Hematopoietic Stem Cells These are building blocks of the blood and immune systems.
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Cell differentiation

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History of stem cells


Stem cells themselves have actually been around for almost as long as life has been on earth. In essence all life evolved from stem cells of some kind. Stem cell field research developed from studies in the 1960s by Canadian scientists Ernest A. McCulloch and James E. Till .
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Forty-four years later, they have been honoured with the 2005 Albert Lasker award for Basic Medical Research, an award often referred to as "America's Nobel."

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Drs. Ernest McCulloch (left) and James Till


(Irma Council for the Canadian Medical Hall of Fame)

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History of Human Stem Cell Research


In 1968, the first bone marrow transplant was successfully used in treatment of SCID Since the 1970s, bone marrow transplants have been used for treatment of immunodeficiencies and leukemias

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Bone Marrow Stem Cells

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History of Human Embryonic Cell Research


1954 John Enders received a Nobel prize in Medicine for growing polio virus in human embryonic kidney cells

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History of Human Embryonic Stem Cell Research


In 1998, James Thomson (University of WisconsinMadison) isolated cells from the inner cell mass of the early embryo, and developed the first human embryonic stem cell lines.  In 1998, John Gearhart (Johns Hopkins University) derived human embryonic germ cells from cells in fetal gonadal tissue (primordial germ cells).


Pluripotent stem cell lines were developed from both sources

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History of Somatic Cell Nuclear Transfer (Cloning)


1952 Briggs and King cloned tadpoles 1996 The first mammal cloned from adult cells was Dolly, the sheep.  1998 Mice cloned
 

1998 Cows cloned 2000 Pigs cloned


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History of Cloning
2001 Cat cloned
   

CC Carbon Copy

2002 Rabbits cloned 2003 Mule cloned 2004 Bull serial-cloned 2005 Dog cloned

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Kinds of Stem Cells


Stem cell type
Totipotent

Description

Examples

Cells from early Each cell can develop (1-3 days) into a new individual embryos Cells can form any (over 200) cell types Some cells of blastocyst (5 to 14 days)

Pluripotent

Multipotent

Cells differentiated, Fetal tissue, cord but can form a number blood, and adult of other tissues stem cells
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Types of Stem cells


1. Embryonic stem cells 2. Adult stem cells

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Embryonic stem cell


Derived from the inner cell mass Pluripotent Can develop into more than 200 different cells Differentiate into cells of the 3 germ cell layers Because of their capacity of unlimited expansion and pluripotency useful in regenerative medicine
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Two Sources of Embryonic Stem Cells


1. Excess fertilized eggs from IVF (in-vitro fertilization) clinics 2. Therapeutic cloning (somatic cell nuclear transfer)

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Excess fertilized eggs from IVF (in-vitro fertilization) clinics Tens of thousands of frozen embryos are routinely destroyed when couples finish their treatment. These surplus embryos can be used to produce stem cells. Regenerative medical research aims to develop these cells into new, healthy tissue to heal severe illnesses.
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Therapeutic cloning (somatic cell nuclear transfer)


The nucleus of a donated egg is removed and replaced with the nucleus of a mature, "somatic cell" (a skin cell, for example). No sperm is involved in this process, and no embryo is created to be implanted in a woman s womb. The resulting stem cells can potentially develop into specialized cells that are useful for treating severe illnesses.
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Tissue or adult stem cells


They produce cells specific to the tissue in which they are found They are relatively unspecialized However they are predetermined to give rise to specific cell types when they differentiate Eg: haematopoietic, bone marrow, neural

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Other types of stem cells


Umbilical cord blood stem cells
Cord blood that is taken from the umbilical cord after the baby is born contains stem cells. Cord blood stem cells can grow a complete immune system of blood cells.
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Induced pluripotent stem cells

Induced pluripotent stem cells are adult cells that have been genetically reprogrammed to an embryonic stem cell-like state

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Properties of Stem cells


Self renewal - the ability to go through numerous cycles of cell division while maintaining the undifferentiated state. Potency the capacity to differentiate into specialized cell types.

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Totipotent stem cells (Total)


Cells produced by the first few divisions of the cell . So can form any cell of the embryo as well as the placenta. Total potential to differentiate into any adult cell type Total potential to form specialized tissue needed for embryonic development
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Pluripotent (plural)
Potential to form most or all 210 differentiated adult cell types These cells differentiate into cells derived from the three germ cell layers. Eg: embryonic stem cell, embryonic germ cell and embryonic carcinoma cells.

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Multipotent (multiple)
Limited potential Forms only multiple adult cell types (These cells can produce cells of a closely related family of cells). Eg: haematopoeitic stem cells, neural and mesenchymal stem cells
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Unipotent these cells only produce one cell type., but have the property of self renewal which distinguishes them from the non stem cells.

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Resources of Stem cells


Umbilical Cord Bone Marrow Peripheral Blood Amniotic Fluid Adipose Tissue Embryonic

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Application of stem cells


A. Stem cell research:
1. It provides an ideal model for the study of development of organisms 2. It replaces damaged cells of the body 3. It also aids in drug discovery

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B. Regenerative medicine

and C. Therapeutic issues

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Therapeutic applications of embryonal stem cells ES cell


The potential to form 200 or more cells. Hence used in regenerative medicine in cases like cardiac failure, Parkinsons disease, diabetes. These cells are being coaxed to differentiate into cardiomyocytes, neural stem cells, insulin producing cell and even germ cells.
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Fetal stem cells


Hematopoietic stem cell:
- characterized by the presence of CD 34 Seen in the umbilical cord and fetal liver - Have a higher cloning efficiency and generates more progenitors than adult bone marrow. - They have a huge competitive engraftment advantage relative to the adult bone marrow. - Fetal liver is now used to treat fetuses having X-Linked SCID.
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Haematopoietic stem cells used in patients whose haematopoietic system has to be replaced They are used in 1.Providing a functional immune system in a person with SCID. 2.Replacing a defective blood system with a functional one who has non malignant genetic disorder like sickle cell anaemia and thallasemia. 3.Restoring the haematopoietic system in cancer patients after treatment.
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Other fetal cells are Mesenchymal stem cells-differentiate to bone, fat and cartilage like the adult counterpart. Neural stem cell- they differentiate into neurons, astrocytes and oligodendrocytes. They are the main source of cells for degenerative CNS injury for replacement. Eg: parkinsons disease
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Potential application of fetal stem cells


1. 2. 3. In the field of fetal medicine: Non invasive prenatal diagnosis Intrauterine stem cell transplantation Gene therapy

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Cord blood stem cells


Cord blood that is taken from the umbilical cord after the baby is born contains stem cells. Cord blood stem cells can grow a complete immune system of blood cells.

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Cord blood is rich in stem cells that are normal and free of malignancies. A typical cord blood collection has sufficient numbers of stem cells for engraftment in most recipients weighing up to 110 lb. Research for replicating stem cells, in vitro, is successfully being done to expand the volume.

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Umbilical cord blood stem cells


It has both mesenchymal blood cell and haematopoietic stem cells. 1st successful umbilical cord blood transplantation in 1989 in a patient with Fanconis anaemia.

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Cord Blood Stem Cells have untapped potential


Cord blood stem cells can be easily collected and stored Long-term cryopreservation has no adverse effect Clinical studies over the past 20 years demonstrate the efficacy and safety of cord blood stem cells Currently, cord blood-derived stem cells have clinically utility in more than 70 diseases Banking cells for future therapies has been validated by science Cord blood stem cells possess significant future potential through expansion, gene therapy, and cell-specific therapies
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Uses for cord blood stem cells


Nearly 40 years ago, the first bone marrow transplant offered new hope for patients with leukemia. Since 1990, stem cell transplants are more prevalent than bone marrow transplants because of ease of collection.
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Today, umbilical cord blood, with its high concentration of hematopoietic stem cells, brings these types of transplantations into the 21st century. Cord blood stem cells have been used to treat more than 45 malignant and genetic diseases. Leukemia is the most common.
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Potential future uses for stem cells


Current research shows great promise for the treatment of heart disease, liver disease, diabetes, stroke, multiple sclerosis, Alzheimers disease, Parkinsons disease, spinal cord injury, and systemic lupus.

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Stored cord blood stem cells from a child is the perfect match for that child. This allows for an autologous transplant if needed, with no risk of Graft-vs- Host Disease(GVHD). GVHD is where the body rejects the donors stem cells and may prevent engraftment from occurring. Cord blood stem cells are a close match for siblings or family members in case of need, with low risk of GVHD.
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Making a decision to collect your babys cord blood stem cells.


Yes, if there is a family history of malignant, benign or inherited disorders. Yes, even in the absence of health risk factors, as there are potential benefits to your family in the future. Yes, if the costs are affordable and this is something of value to you. Yes, it is the one chance to collect them.
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Collecting cord blood stem cells


This blood is collected by the physician after the baby is born and the cord is cut. It takes less than 5 minutes and there is no pain, harm or risk to mother or newborn. This cord blood containing the stem cells, is sent to a Cord Blood Bank either private or public where it is processed and the stem cells are preserved in liquid nitrogen.

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Haematopoeitic stem cells


Derived from bone marrow in adults and umbilical cord blood Option given to the parents regarding stem cell banking during antenatal visits 25% chance that sibling also can have a perfect match

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Blood is collected from umbilical cord immediately after delivery about 100-150cc The number of cells in 1 ml is 40,000 They are stored in blood banks at 196deg celsius in a state of suspended animation and restart their activity on thawing
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Advantages over bone marrow cells


1. 2. 3. 4. 5. 6. 7. 8. 9. High rate of engraftment More tolerant to tissue matches Less severe GVHD Rarely contaminated with latent virus Easy to collect, not painful Superior proliferative capacity Greater immunological naievity Unlimited supply Lower cost
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Ailments for which stem cells are being used now


Acute leukemias Chronic leukemias Myelodysplastic syndromes Marrow failure Myeloproliferative disorders Lymphoproliferative disorders
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Phagocyte disorders Inherited disorders like Lesch Nyhan syndrome, beta Thallesemia etc Inherited platelet abnormalities Inherited metabolic disorders like Mucopolysaccharidosis, Hurlers syndrome, Krabbe disease, Niemannpick disease etc

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Histocytic disorders Inherited erythrocyte abnormalities Inherited immune system disorders like ataxia telangectesia, DiGeorge syndrome, SCID etc Plasma cell disorder Malignancies like neuroblastoma, Ewing sarcoma, Renal cell CA etc
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Trials underway
Cardiac disease Diabetes Multiple Sclerosis Muscular Dystrophy Parkinsons disease Spinal cord injury Stroke
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Future stem cell application


Alzheimers Disease Lupus Rheumatoid arthritis

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Research is going on regarding the use of stem cells for male infertility in mouse However the progeny has severe abnormalities Also recent research suggests that oocyte can be generated from stem cells originating from Bone marrow- haematopoietic stem cells Ovarian surface cells
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Ethical issues Are we trying to play GOD? Is embryo a person? Will stem cell research encourage embryo destruction and abortions?
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Guidelines for stem cell research in India


Compulsory registration of the existing cell lines to be registered under specific apex bodies in the field Genetic research dealing with human egg or sperm and genetic engineering and then transfer of human blastocysts will not be allowed
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Research and therapy using fetal/placental stem cell will be allowed Termination of pregnancy cannot be sought for donating fetal tissue for therapeutic or financial benefits

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All the umbilical cord blood banks should be registered with Drug Controller General of India Research into human cloning is not to be done

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These guidelines are aimed to encourage development of sound research and therapy, prevent any misuse of human embryos and fetuses and protect patients from fraudulent treatments in the name of stem cell research.

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