Download - Stem cell therapy
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Stem cell therapy
Moderator Dr. Mohd. Tariq SalmanResident Dr. Karun Kumar (JR-II)
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Properties of stem cells
•If the cell is able to form all cell types of
the embryo & adult (Fertilized egg cell)
Totipotent stem cell
•Stem cell able to differentiate into all 3
germ layers Pluripotent stem cell
(Embryonic stem cell)
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•Multipotent stem cell Differentiate to
form cells of some but not all 3 germ
layers (Bone, cartilage, connective
tissue)
•Unipotent stem cell Able to form just
one other cell type (Spermatogonia)
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Types of stem cells
1. Embryonic stem cells Stem cells
harvested from a blastocyst
(pluripotent)
2. Adult (Somatic) stem cells Stem cells
harvested from tissues in an adult
body (multipotent)
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Haematopoietic stem cell
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Site of haematopoiesis
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Stem cell division
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On the road to stem cell therapy•Interest in human embryonic stem cells Shortage of donor organs•First-in-man studies aimed at reversing macular degeneration have already taken place in London, and around 25 patients have been included in the first phase 1 studies (safety and feasibility) worldwide.
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Stem cell timelineYear Discovery
1956 First successful bone marrow transplant
1981 Embryonic stem cells are isolated from mouse blastocysts (Martin Evans, UK)
1988 Haemopoietic stem cells from adult mice are purified and characterized
1997 Dolly the sheep (Ian Wilmut, Edinburgh)
1998 First human embryonic stem cells are isolated
2001 Mouse embryonic stem cells are created by nuclear transfer
2002 Pancreatic stem cells derived from mouse embryonic stem cells cure diabetes in mice
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Year Discovery
2004 Type of nerve cell lost in Parkinson’s disease is produced from human embryonic stem cells
2005 Human embryonic stem cells were shown to differentiate into active functioning nerve cells when placed in mouse brains
2005 Pancreatic cells were derived from adult stem cells
2006 Embryonic stem cells were derived from the morula of a mouse
2006 Embryonic stem cells were first grown without animal products in the culture
2010 Person with spinal injury first to receive medical treatment derived from human embryonic stem cells
2012 Human embryonic stem cells show promise in treating blindness
2013 Human embryonic stem cells produced from fetal cells using therapeutic cloning
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Year Discovery
2014 Charles Vacanti (Harvard Medical School) and Haruko Obokata (Riken Center for Developmental Biology) announced that any cell can potentially be rewound to a pre-embryonic state using a simple 30 minute technique
2014 Teams led by Dieter Egli of the New York Stem Cell Foundation and Young Gie Chung from CHA University in Seoul, South Korea, independently produce human embryonic stem cells from adult cells, using therapeutic cloning. Egli's team use skin cells from a woman with diabetes and demonstrate that the resulting stem cells can be turned into insulin-producing beta cells. In theory, the cells could be used to replace those lost to the disease.
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STAP Stimulus triggered acquisition of pluripotency
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Mouse embryo made with reprogrammed cells
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Stem cell research fraud (2014)
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Battle against baldness (CNBC 29th January, 2015)
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Battle against multiple sclerosis (29/1/15)
Dr. Mark Freedman of the Ottawa Hospital Research Institute is leading research to determine if a type of stem cell can help alleviate the symptoms of multiple sclerosis
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Professor Anthony Hollander, a cartilage tissue engineer, who cultured stem cells from ClaudiaCastillo to build a new windpipe (trachea) in year 2008
Claudia Castillo, who received a transplanted windpipe that was engineered from her ownstem cells
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Dr. De Luca with Claudio
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Type 1 Diabetes
•Abnormal activation of the immune system Destruction of the insulin-producing beta cells•Beta cells from pluripotent stem cells or adult progenitors in the pancreas Source of cells for treatment of diabetes
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Spinal cord injury
•Oligodendrocyte cells that produce myelin can be generated from stem cells; if these are injected into the site of the crush injury they could repair the myelin layer locally, and thus restore function and cure the paralysis
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Demyelinating diseases
•Fetal tissue can also be a source of myelinating cells and, although also controversial, various trials are ongoing
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Making the blind see•Problem with corneal transplants•Few human donors to meet clinical need•Unsuitable in destruction of limbus
•Alternative Cultivation of limbal cells
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Macular degeneration Retinitis pigmentosa
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Eye an ideal organ for stem cell transplant1. Immune-privileged site •Transplanted cells that are not HLA matched are not rejected •Immunosuppressive medication is not required
2. Eye is a “ closed” unit (any stem cells injected would find it difficult to misbehave and escape to other parts of the body)
3. We have two eyes, it may be possible to treat one eye without the risk of losing vision altogether
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•Human embryonic and pluripotent stem cells can easily differentiate into retinal pigment epithelial cells, the cells that need replacing
Cells are cultured & surgically inserted into the retina
↓Pick up signals from light & transmit
images to the brain
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Deafness•Inner ear hair cells can be generated from pluripotent stem cells, both from mice and humans•When the stem cell derived inner ear hair cells from mice are transplanted to the ears of mice in which deafness was induced by the same chemotherapy reagents as used to treat cancer, their hearing was restored
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Best stem cell for transplantation•Acute & life-threatening disease (MI) Allogenic & derived from
1. Living (bone marrow)2. Deceased (Insulin producing beta cells)
•Chronic disease Autologous stem cell transplantation
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Bone marrow transplantation by stem cell mobilizationStem cells are collected from blood after giving certain growth factors (e.g. GM-CSF) to the patients
↓These growth factors temporarily recruit stem cells from the bone marrow into the blood which are stored till needed
↓The patient is treated with cytostatic drugs (chemotherapy) or undergoes irradiation
↓
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The blood stem cells can subsequently be returned to the blood of the patient at any chosen time point through a simple intravenous infusion into the blood stream
↓They will find their own way back “home” to the bone marrow, where they will settle and start producing new blood cells, at no risk of rejection since they are the patient’s own cells
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Where to transplant stem cells1. Myocardial infarction New cardiac
cells have to be transplanted directly into the heart muscle
2. Kidney disease Replacing kidney cells with stem cell derivatives will need the transplanted cells to exert their function within the kidney itself
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3.Diabetes Any replacement beta cells, from stem cells or pancreas progenitors could be transplanted at another site in the body and not in pancreas. (The portal vein of the liver, to which the cells can be delivered simply under local anesthetic is being used as a transplantation site for beta cells from donors)
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4. Parkinson’s disease Challenge because the distance to which neuritis grow cannot be predicted. Dopaminergic nerve cells in the brain exert their effect through the neuritis (at a site distant from where the cell body “sits” in the brain)•In mice and rats the neurites from these neurons can easily grow out over that distance, but in the much larger human brain, this can be several centimeters and is very difficult.
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Cell types available for stem cell transplantation1. First isolated from large intestine of
mice•These cells self organize into “organoids” or “miniguts” •Use To treat intestinal conditions in which the intestinal epithelial layer is damaged (ulcers)
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2. Hematopoietic stem cells obtained from umbilical cord blood Enable reconstitution of the blood cell population of a patient after destructive chemotherapy •2 or more matched cord blood samples are required for one adult patient
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Intestinal organoids
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The future : Cerebral organoids
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Umbilical cord blood bank
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Transplantation of stem cells : Where we stand ?•Most commonly used experimental animals Mice because
1. There are many different strains of mice with mutations in their DNA that are similar to those causing human disease
2. Easy to handle 3. Inexpensive to keep
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Stem cells can differentiate in vitro to cells that resemble oligodendrocytes
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Clinical trials without patients ? (Organs-on-chips)
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Vision of the future Cancer metastasis on a chip
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Lung-on-a chip
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Applications of organs on a chip1. Drug toxicity screening (Heart and liver
most susceptible organs)2. Human disease models (Development of
novel drugs to treat the illness)3. Investigate routes for optimal drug uptake
in the body (Eg. To measure the rate of transport through the intestinal wall after oral intake)
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4. By capturing the genetic variation in the normal and sick human population, these models are expected to increase the speed and reduce costs of drug development. 5. Safe and effective drug development tuned to the specific genetic profile of the patient (Personalized medicine)
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Thank you