Stem Cell Therapy

STEM CELL STEM CELL THERAPYTHERAPY

PRESENTED PRESENTED BYBY

DR.GANGA.TDR.GANGA.TJSSMC.JSSMC.

MYSOREMYSORE..

Stem cellsStem cells RareRare

Primitive cellsPrimitive cells

Defined by their capacity to Defined by their capacity to self renew as well as self renew as well as differentiate into one or differentiate into one or more mature cell typesmore mature cell types..

Two broad types seen:Two broad types seen:

A – embryonic stem cellsA – embryonic stem cells

B – adult stem cellsB – adult stem cells

Embyronic stem cellEmbyronic stem cell Derived from the inner cell massDerived from the inner cell mass PluripotentPluripotent Can develop into more than 200 Can develop into more than 200

different cellsdifferent cells Differentiate into cells of the 3 Differentiate into cells of the 3

germ cell layersgerm cell layers Because of their capacity of Because of their capacity of

unlimited expansion and unlimited expansion and pluripotency – useful in pluripotency – useful in regenerative medicine regenerative medicine

Tissue or adult stem Tissue or adult stem cellscells

They produce cells specific to the They produce cells specific to the tissue in which they are foundtissue in which they are found

They are relatively unspecializedThey are relatively unspecialized However they are predetermined However they are predetermined

to give rise to specific cell types to give rise to specific cell types when they differentiatewhen they differentiate

Eg: haematopoietic, bone marrow, Eg: haematopoietic, bone marrow, neuralneural

PropertiesProperties Self renewalSelf renewal - the ability to go - the ability to go

through numerous cycles of through numerous cycles of cell division while maintaining cell division while maintaining the undifferentiated state.the undifferentiated state.

PotencyPotency – the capacity to – the capacity to differentiate into specialized differentiate into specialized cell types.cell types.

Totipotent stem cellsTotipotent stem cells - -cells produced by the first cells produced by the first few divisions of the cell . few divisions of the cell . So can form any cell of the So can form any cell of the embryo as well as the embryo as well as the placenta.placenta.

PluripotentPluripotent – these cells – these cells differentiate into cells differentiate into cells derived from the three derived from the three germ cell layers.germ cell layers.

Eg: embryonic stem cell, Eg: embryonic stem cell, embryonic germ cell and embryonic germ cell and embryonic carcinoma cells. embryonic carcinoma cells.

MultipotentMultipotent – these cells can – these cells can produce cells of a closely produce cells of a closely related family of cells.related family of cells.

Eg: haematopoeitic stem Eg: haematopoeitic stem cells, neural and cells, neural and mesenchymal stem cellsmesenchymal stem cells

UnipotentUnipotent – these cells – these cells only produce one cell only produce one cell type., but have the type., but have the property of self renewal property of self renewal which distinguishes them which distinguishes them from the non stem cells. from the non stem cells.

Application of stem Application of stem cellscells

Stem cell research:Stem cell research:

1. It provides an ideal model for 1. It provides an ideal model for the study of development of the study of development of organismsorganisms

2. It replaces damaged cells of 2. It replaces damaged cells of the bodythe body

3. It also aids in drug discovery3. It also aids in drug discovery

Regenerative medicine andTherapeutic issues

Therapeutic Therapeutic applications of applications of

embryonal stem cells –embryonal stem cells –ES cellES cell

The potential to form 200 or more The potential to form 200 or more cells.cells.

Hence used in regenerative Hence used in regenerative medicine in cases like cardiac medicine in cases like cardiac failure, Parkinsons disease, failure, Parkinsons disease, diabetes.diabetes.

These cells are being coaxed to These cells are being coaxed to differentiate into cardiomyocytes, differentiate into cardiomyocytes, neural stem cells, insulin neural stem cells, insulin producing cell and even germ cells.producing cell and even germ cells.

Safety concernSafety concern Potential to form Potential to form

teratomas after teratomas after transplantationtransplantation

Hence to produce pure Hence to produce pure differentiated cells.differentiated cells.

Risk of transfer of Risk of transfer of xenopathogensxenopathogens

Immunological Immunological barriersbarriers

Rejection-Rejection- mediated by class 1 MHC and by antigen presenting cells harbouring the class 2 MHC antigen

Can be overcome by generating large MHC homozygous ES cell banks, and the production of patient specific ES cell via Somatic Cell Nuclear Transfer.

ES cells are used as ES cells are used as models for developmental models for developmental biology like early biology like early embryonic differentiation embryonic differentiation and understanding the and understanding the pathogenesis of specific pathogenesis of specific genetic diseases.genetic diseases.

Stem cells and Stem cells and diseasesdiseases

The best studied stem cells are The best studied stem cells are the haematopoietic and the the haematopoietic and the male germ cells.male germ cells.

Some of the prominent Some of the prominent diseases treated include diseases treated include leukemia, anaemia, thallesemia leukemia, anaemia, thallesemia and myelodysplastic syndrome.and myelodysplastic syndrome.

Allogenic BMT is another well Allogenic BMT is another well known procedure done.known procedure done.

Fetal stem cellsFetal stem cells Haematopoietic stem cell: charecterised 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.

Haematopoietic stem cells used in Haematopoietic stem cells used in patients whose haematopoietic patients whose haematopoietic system has to be replacedsystem has to be replaced

They are used in They are used in 1.Providing a functional immune 1.Providing a functional immune

system in a person with SCID.system in a person with SCID.2.Replacing a defective blood system 2.Replacing a defective blood system

with a functional one who has non with a functional one who has non malignant genetic disorder like malignant genetic disorder like sickle cell anaemia and sickle cell anaemia and thallasemia. thallasemia.

3.Restoring the haematopoietic 3.Restoring the haematopoietic system in cancer patients after system in cancer patients after treatment.treatment.

Transplantation can be Transplantation can be

1.1. AutologousAutologous

2.2. SyngeneicSyngeneic

3.3. AllogenicAllogenic

GVHD is least when there is GVHD is least when there is genetic identity.genetic identity.

Other fetal cells are Other fetal cells are Mesenchymal stem cells-Mesenchymal stem cells-

differentiate to bone, fat and differentiate to bone, fat and cartilage like the adult counterpart.cartilage like the adult counterpart.

Neural stem cell-Neural stem cell- they differentiate they differentiate into neurons, astrocytes and into neurons, astrocytes and oligodendrocytes. They are the main oligodendrocytes. They are the main source of cells for degenerative CNS source of cells for degenerative CNS injury for replacement.injury for replacement.

Eg: parkinson’s disease Eg: parkinson’s disease

Potential application Potential application of fetal stem cellsof fetal stem cells

In the field of fetal medicine:

1. Non invasive prenatal diagnosis

2. Intrauterine stem cell transplantation

3. Gene therapy

Umbilical cord blood Umbilical cord blood stem cellsstem cells

It has both mesenchymal It has both mesenchymal blood cell and blood cell and haematopoietic stem cells.haematopoietic stem cells.

11stst successful umbilical successful umbilical cord blood transplantation cord blood transplantation in 1989 in a patient with in 1989 in a patient with Fanconi’s anaemia.Fanconi’s anaemia.

Haematopoeitic Haematopoeitic stem cellsstem cells

Derived from bone marrow in Derived from bone marrow in adults and umbilical cord adults and umbilical cord bloodblood

Option given to the parents Option given to the parents regarding stem cell banking regarding stem cell banking during antenatal visitsduring antenatal visits

25% chance that sibling also 25% chance that sibling also can have a perfect matchcan have a perfect match

Blood is collected Blood is collected from umb cord from umb cord immediately after immediately after delivery about delivery about 100-150cc100-150cc

The number of The number of cells in 1 ml is cells in 1 ml is 40,00040,000

They are stored in They are stored in blood banks at blood banks at -196deg -196deg celsius in a state celsius in a state of suspended of suspended animation and animation and restart their restart their activity on thawingactivity on thawing

Advantages over bone Advantages over bone marrow cellsmarrow cells

1.1. High rate of engraftmentHigh rate of engraftment2.2. More tolerant to tissue matchesMore tolerant to tissue matches3.3. Less severe GVHDLess severe GVHD4.4. Rarely contaminated with latent Rarely contaminated with latent

virusvirus5.5. Easy to collect, not painfulEasy to collect, not painful6.6. Superior proliferative capacitySuperior proliferative capacity7.7. Greater immunological naievityGreater immunological naievity8.8. Unlimited supplyUnlimited supply9.9. Lower costLower cost

Ailments for which Ailments for which stem cells are being stem cells are being

used nowused now Acute leukemiasAcute leukemias Chronic Chronic

leukemias leukemias Myelodysplastic Myelodysplastic

syndromessyndromes Marrow failureMarrow failure MyeloproliferatiMyeloproliferati

ve disordersve disorders LymphoproliferaLymphoprolifera

tive disorderstive disorders

Phagocyte disordersPhagocyte disorders Inherited disorders like Inherited disorders like

Lesch Nyhan syndrome, beta Lesch Nyhan syndrome, beta Thallesemia etcThallesemia etc

Inherited platelet Inherited platelet abnormalities abnormalities

Inherited metabolic disorders Inherited metabolic disorders like Mucopolysaccharidosis, like Mucopolysaccharidosis, Hurler’s syndrome, Krabbe Hurler’s syndrome, Krabbe disease, Niemann- pick disease, Niemann- pick disease etcdisease etc

Histocytic disordersHistocytic disorders Inherited erythrocyte Inherited erythrocyte

abnormalitiesabnormalities Inherited immune system Inherited immune system

disorders like ataxia disorders like ataxia telangectesia, DiGeorge telangectesia, DiGeorge syndrome, SCID etcsyndrome, SCID etc

Plasma cell disorderPlasma cell disorder Malignancies like neuroblastoma, Malignancies like neuroblastoma,

Ewing sarcoma, Renal cell CA etcEwing sarcoma, Renal cell CA etc

Trials underwayTrials underway Cardiac diseaseCardiac disease DiabetesDiabetes Multiple SclerosisMultiple Sclerosis Muscular DystrophyMuscular Dystrophy Parkinson’s diseaseParkinson’s disease Spinal cord injurySpinal cord injury StrokeStroke

Future stem cell Future stem cell applicationapplication

Alzheimer’s DiseaseAlzheimer’s Disease LupusLupus Rheumatoid arthritisRheumatoid arthritis

Research is going on Research is going on regarding the use of stem regarding the use of stem cells for male infertility in cells for male infertility in mousemouse

However the progeny has However the progeny has severe abnormalitiessevere abnormalities

Also recentAlso recent research research suggests that oocyte can suggests that oocyte can be generated from stem be generated from stem cells originating from cells originating from

1.1. Bone marrow- Bone marrow- haematopoietic stem cellshaematopoietic stem cells

2.2. Ovarian surface cellsOvarian surface cells

Ethical issuesEthical issuesAre we trying to play Are we trying to play

GOD?GOD? Is embryo a person?Is embryo a person?Will stem cell research Will stem cell research

encourage embryo encourage embryo destruction and abortions?destruction and abortions?

Guidelines for stem Guidelines for stem cell research in Indiacell research in India

Compulsory registration of the Compulsory registration of the existing cell lines to be existing cell lines to be registered under specific apex registered under specific apex bodies in the fieldbodies in the field

Genetic research dealing with Genetic research dealing with human egg or sperm and genetic human egg or sperm and genetic engineering and then transfer of engineering and then transfer of human blastocysts will not be human blastocysts will not be allowedallowed

Research and therapy Research and therapy using fetal/placental stem using fetal/placental stem cell will be allowedcell will be allowed

Termination of pregnancy Termination of pregnancy cannot be sought for cannot be sought for donating fetal tissue for donating fetal tissue for therapeutic or financial therapeutic or financial benefits benefits

All the umbilical cord All the umbilical cord blood banks should be blood banks should be registered with Drug registered with Drug Controller General of Controller General of IndiaIndia

Research into human Research into human cloning is not to be donecloning is not to be done

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