adult stem cell and its transdifferentiation

7/28/2019 Adult Stem Cell and Its Transdifferentiation

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Dr .Jayachandran.V P.G-2 nd year


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7/21/2013Dr. Hariom Yadav

Importance of Stem Cell Research


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1998 - Researchers first extract stem cells from humanembryos

1999 - First Successful human transplant of insulin-makingcells from cadavers

2001 - President Bush restricts federal funding for embryonic stem-cell research

2002 - Juvenile Diabetes Research FoundationInternational creates $20 million fund-raising effortto support stem-cell research

2002 - California ok stem cell research2004 - Harvard researchers grow stem cells from embryos

using private funding2004 - Ballot measure for $3 Billion bond for stem cells

Stem Cell History


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A cell that has the ability to continuously divide and differentiate (develop) into

various other kind(s) of cells/tissues


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Blank cells (unspecialized)

Capable of dividing and renewing themselves for long periods of tim(proliferation and renewal)

Have the potential to give rise to specialized cell types (differentiatio


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Cell CommitmentCells make Decisions Decisions determine cells

fateThought to be irreversible


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By two mechanisms:(A)obligatory asymmetric replication

Each stem cell division,

One of the daughter cells retains its self-renewing capacityOther enters a differentiation pathway,

(b)stochastic differentiation,Stem cell population is maintained by the balance between stem cell dThat generate either two self-renewing stem cells or two cells that wildifferentiate


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Two identical daughters Self-renewal Differentiate

Somatic Cell Stem Cell


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Embryonic Stem CellsBlastocyst inner cell massEpiblast Embryonic/fetal germ cells

Fetal (some consider adult) Stem Cells Umbilical Cord Blood (UCB) SCs Amniotic Fluid Stem Cells


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Totipotent stem cells- can form the extraembryonic tissues of thembryo and all cells of organism. e.g Zygote

Pluripotent stem cells- can form all the cell types of the adult organism. e.g. embryonic stem cells from inner cell mass

Multipotentstem cells- have the ability to form all the differentcell types of a given tissue. In some cases, a tissue contain few or one differentiated lineage and the stem cells that mthe lineage are described asoligopotent or unipotent respectively.e.g. Adult stem cells or progenitor cells.


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What are stem cells?


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Adult stem cells Embryonic stem cells Typically reside in or near their tissue

Are capable of giving rise to functional cells in their tissue (but not other tissue types)

Are typically found only in tissuesthat undergo regular turnover.

Decrease in both number and activity as one ages.

Created from inner cell mass cells thexist only in very early embry

Are capable of giving rise to all ofcell types in the body including no

regenerative

Can be divided many times (possindefinitely) in culture to make m

cells.


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Zygote Morula Blastocyst


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Trophoectoderm (placenta and amnion)

Inner cell mass(all tissues in the body)

1/100 inch


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Ectoderm

Outer surface

Skin

CNS

Neuron

Neural Crest

Melanocyte

Mesoderm Endoderm

Dorsal

Notochord

Paraxial

Bone tissue

Intermediate

Tubule cell of the kidney

Lateral

Red Blood Cell

Blood vessels

Heart

Head

Facial Muscle

Digestive Tube

Pancreatic Cell

Pharynx

Thyriod Cell

Respiratory Tube

Alveolar Cell

Germ Cells

Germ Cells

Sperm and Egg


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Time of Gestation After Birth

Endoderm

Mesoderm

Ectoderm

Germ

SpermOr Eggs

Skin

Brain

Heart

Blood

Gut

InnerCellMass


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Endoderm

Mesoderm

Ectoderm

Germ

SpermOr Eggs

Skin

Brain

Heart

Blood

Gut

Scientists have figured out how to make inner cell mass cells self-renew in plastic dishes.

A few hundred cellsfrom one embryo can be grown into at least 1.3 1031cells creating a stem cell line.

Embryonic Stem Cell


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Eggs collected for in-vitro fertility treatment cannot be easily frozen and stored. Early embryos created after the combination of sperm and eggs can be frozen.

An excess of embryos are created as the process of egg collection is painf

dangerous and expensive. For most couples, more embryos are created than are needed to have a desired number of children.


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Patient-Specific Stem Cells

Unfertilized egg Fusion with patientscell

Fertilized egg equivalent

Blastocyst


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Derived from 4-5 day old embryos (Prior to implantation in uterus)

Indefinite proliferative capacity (immortal) making a stem cell line

Can become any cell type in the body

The only cells that definitely can become heart muscle cells and other clinimportant cell types.

Allows experiments that would be otherwise impossible.


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1 Heart Disease

2 Cancer

3 Stroke

4 Chronic Lung Diseases

5 Accidents

6 Diabetes Mellitus7 Influenza and Pneumonia

8 Alzheimers Disease

9 Kidney Disease

10 Sepsis

11 Suicide

12 Chronic Liver Disease

13 Homicide

14 High Blood Pressure

15 Lung Inflammation after Aspiration CDC NCHS

Leading Causes of Death in the US (2001)


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Undifferentiated CellsFound throughout the body after embryonic development Multiply by cell division to replenish dying cells

Regenerate Damaged Tissues.


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HematopoieticMammaryMesenchymalNeural

EndothelialOlfactoryNeural crestTesticular


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A hierarchy of stem cellsSelf maintenanceProliferation,clonogenicity and genomic integrity

Adult stem cell identity Molecular control of stem cell behaviour


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Basis for generating tissue for transplantation

Differentiate into cell types in organs / tissues other than those ex from the cells predicted lineage


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Three types of stem cell originate in bone marrow:

1. Hematopoietic Stem Cell 2. Stromal Cells 3. Endothelial Progenitor Cells


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Endothelial Progenitor Cells

Skeletal Muscle Stem Cells

Epithelial Cell Precursors in the Skin and Digestive System

Stem Cells in the Pancreas and Liver


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stemcells.nih.gov/.../images/figure2_lg.jpg


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The therapies require a stem cell source of the specific lineage and hor culturing them up to the numbers required is a challenge.


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Process of creating living, functional tissues to repair or replace tissue function lost due to age, disease, damage, or congenital defects

It helps to produce extended healthy longevity,


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Leukemia results when white blood cells made in bone marrow begiand function abnormally

One way to do this is through chemotherapy

When chemotherapy cannot solve the problem, doctors turn to marrow transplants.


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A degenerative disorder of thecentral nervous system

Sufferers lack a sufficient amount of a brain chemical

called dopamine

The cure of this disease is to multiply cells that releasedopamine
http://en.wikipedia.org/wiki/Central_nervous_systemhttp://www.physorg.com/tags/brain+chemical/http://www.physorg.com/tags/brain+chemical/http://www.physorg.com/tags/brain+chemical/http://www.physorg.com/tags/brain+chemical/http://en.wikipedia.org/wiki/Central_nervous_systemhttp://en.wikipedia.org/wiki/Central_nervous_systemhttp://en.wikipedia.org/wiki/Central_nervous_systemhttp://en.wikipedia.org/wiki/Central_nervous_systemhttp://en.wikipedia.org/wiki/Central_nervous_system


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There is insulin independence for Type 1 diabetes patients

A study showed patients receiving injections with adult stem cells w

to go as long as four years without having to rely on insulin shots.


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Cardiologists and heart surgeons worldwidecurrently use VesCell adult stem cell therapy to treat patients suffering from coronary artery disease, cardiomyopathy, and congestive heart failure.


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Bone Marrow taken from the hip 6 weeksof cultivating the adult stem cells toincrease total to 100 million. Adult Stem Cells injected at injury site(C3-C4) in a surgical procedure


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The genetic defect results in red uced rate of synthesis of one of the glochains that make uphemoglobin

Hematopoietic stem cell transplantation (HSCT) is the only capproach
http://en.wikipedia.org/wiki/Hemoglobinhttp://en.wikipedia.org/wiki/Hemoglobinhttp://en.wikipedia.org/wiki/Hemoglobin


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Cancer stem cell s (CSCs) are cancer cells(found within tumors or hematological cancers) that possess ch aracteristicsassociated with normal stem cells, specifically the ability to give rise to all cell types found in a particular cancer sample

Lisa Ray to undergo stem cell transplant for blood cancer
http://en.wikipedia.org/wiki/Tumorhttp://en.wikipedia.org/wiki/Hematological_cancerhttp://en.wikipedia.org/wiki/Hematological_cancerhttp://en.wikipedia.org/wiki/Hematological_cancerhttp://en.wikipedia.org/wiki/Hematological_cancerhttp://en.wikipedia.org/wiki/Tumorhttp://en.wikipedia.org/wiki/Hematological_cancerhttp://en.wikipedia.org/wiki/Hematological_cancerhttp://en.wikipedia.org/wiki/Stem_cellhttp://en.wikipedia.org/wiki/Stem_cellhttp://en.wikipedia.org/wiki/Stem_cellhttp://en.wikipedia.org/wiki/Stem_cellhttp://en.wikipedia.org/wiki/Stem_cellhttp://en.wikipedia.org/wiki/Hematological_cancerhttp://en.wikipedia.org/wiki/Hematological_cancerhttp://en.wikipedia.org/wiki/Hematological_cancerhttp://en.wikipedia.org/wiki/Tumorhttp://en.wikipedia.org/wiki/Cancer


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Easy to obtain Potentially limitless in supply Patients can use their own stem cells for treatment and therapy

Adult stem cells are politically neutral Not offensive to any major interest group nor do they generate contro


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The isolation of some types of ASC, for example the isolation of nfrom a patient's brain, would be impracticalWhere a person suffers from a genetic disorder or some types of cancisolated from that individual will retain the damaging genetic alteunderlying the disease and so be of little therapeutic valueUnambiguous identification is difficultMaintenance in culture is difficult


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The range of commitment options available to a cell

Totipotent

Pluripotent

Multipotent

Oligopotent

Unipotent

Potency


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DOLLY 1997

Decisions not irreversible


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?


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start with cancer cell

Breast cancer Leukemia

Lymphoma Melanoma

Pluripotent Stem Cells

Melanoma Tetraploid Complementation

E9.5


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Avoid ethical issuesEgg donation Matched stem cells

Develop cell-based disease modelsUnderstand the science

Parthenogenesis8-cell Blastomere Altered Nuclear Transfer

Molecular Reprogramming


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Asexual Reproduction Normal in Reptiles; Not seen in MammalsTrick human eggs to undergo in the lab

Immunologically matched to egg donor Universal Donor? Not ViableNo Potential Human Being


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PGD - Preimplantation GeneticDiagnosis

1 of 8 cells removed ACT cultured embryonic stem cell line from one cell


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Idea suggested by Presidents Council on Bioethics Apply a genetic trick in the somatic cell nucleusBlastocyst generated is not viable

No Potential Human BeingProof-of-Principle demonstrated in mice by scientists at MITs Whitehead Institute


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Potency

Goal: Manipulate a somatic cells potency

Totipotent

Pluripotent

Multipotent

Oligopotent

Unipotent

somatic cell


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Cell Fusion

Cell Extract

Cell Explantation

Add Four Factors

pluripotent

pluripotent

+ 4 Factors

pluripotent

x pluripotent


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AFSSCNT

Cancer cells ANT

BlastomereParthenogenesisMolecular Reprogramming

Cell Fusion Cell Extract Cell Explantation Defined Factors


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adult stem cell and its transdifferentiation

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