STEMCELL TRANSPLANTATIO

8/8/2019 STEMCELL TRANSPLANTATIO

1/30

Stem Cell TransplantationStem Cell Transplantation

Helps Patients with Type IHelps Patients with Type I

DiabetesDiabetes


2/30

Presented to you byPresented to you by

Group 4Group 4nn Belarmino, Asther May O.Belarmino, Asther May O.

nn Capaque, Rosa MaeCapaque, Rosa Mae

nn De la Piedra, Jo Ann G.De la Piedra, Jo Ann G.

nn Demao, Jamallodin S.Demao, Jamallodin S.

nn Esplana, Christian M.Esplana, Christian M.

nn Evangelista, Christine Iris C.Evangelista, Christine Iris C.

nn Muga, ChristineMuga, Christine

nn Sanchez, Marianne A.Sanchez, Marianne A.

nn

Viagedor, Jerpon P. Viagedor, Jerpon P.nn Villarin, Nadine Z. Villarin, Nadine Z.

nn Ytem, Jennifer J. Ytem, Jennifer J.


3/30

Type I DiabetesType I Diabetes

nnThis is also known as childhood juvenile orThis is also known as childhood juvenile or

insulin dependent diabetesinsulin dependent diabetes

nnItIts an autoimmune disease that results ins an autoimmune disease that results inthe permanent destruction of insulinthe permanent destruction of insulin

producing beta cells in the pancreasproducing beta cells in the pancreas

nnDetermined by glucose tolerance testDetermined by glucose tolerance test

nnManagement is through insulinManagement is through insulin

replacement therapyreplacement therapy


4/30


5/30

Normal PancreasNormal Pancreas


6/30

Diabetic PancreasDiabetic Pancreas


7/30


8/30

Comparison between type I andComparison between type I and

type II Diabetestype II Diabetes

Usually presentUsually presentPresentPresentHLAHLA

Very strong Very strongModerateModerateGenetic PredispositionGenetic Predisposition

8080--90% of diagnosed90% of diagnosed

diabeticsdiabetics

1010--20% of diagnosed20% of diagnosed

diabeticsdiabetics

PrevalencePrevalence

ObeseObeseFrequently emaciatedFrequently emaciatedPhysique during onsetPhysique during onset

Usually after age 35Usually after age 35(gradual)(gradual)

During puberty orDuring puberty orchildhoodchildhood

Age of Onset Age of Onset

NIDDM, adult onsetNIDDM, adult onsetIDDM, JODIDDM, JODSynonymSynonym

Type II DMType II DMType I DMType I DM


9/30

Stem cellsStem cells

Stem cells differ from other kinds of cells in theStem cells differ from other kinds of cells in the

body. All stem cellsbody. All stem cellsregardless of their sourceregardless of their source

have three general properties:have three general properties:

--they are unspecializedthey are unspecialized

--they are capable of dividing and renewingthey are capable of dividing and renewingthemselves for long periodsthemselves for long periods

--they can give rise to specialized cell typesthey can give rise to specialized cell types


10/30

nn Stem cells are unspecialized.Stem cells are unspecialized.

nn Stem cells are capable of dividing and renewingStem cells are capable of dividing and renewing

themselves for long periodsthemselves for long periods. Unlike muscle cells, blood. Unlike muscle cells, bloodcells, or nerve cellscells, or nerve cellswhich do not normally replicatewhich do not normally replicatethemselvesthemselvesstem cells may replicate many times. Whenstem cells may replicate many times. Whencells replicate themselves many times over it is calledcells replicate themselves many times over it is calledproliferation. A starting population of stem cells thatproliferation. A starting population of stem cells thatproliferates for many months in the laboratory can yieldproliferates for many months in the laboratory can yield

millions of cells. If the resulting cells continue to bemillions of cells. If the resulting cells continue to beunspecialized, like the parent stem cells, the cells areunspecialized, like the parent stem cells, the cells aresaid to be capable of longsaid to be capable of long--term selfterm self--renewal.renewal.


11/30

Adult stem cells Adult stem cells

nn Adult stem cells: Adult stem cells:

nn typically generate the cell types of thetypically generate the cell types of thetissue in which they residetissue in which they reside

exex-- A blood A blood--forming adult stem cell in theforming adult stem cell in thebone marrow, for example, normally givesbone marrow, for example, normally gives

rise to the many types of blood cells suchrise to the many types of blood cells suchas red blood cells, white blood cells andas red blood cells, white blood cells andplatelets.platelets.


12/30

nn adult stem cells have been identified in manyadult stem cells have been identified in many

organs and tissues.organs and tissues.

nn One important point to understand about adultOne important point to understand about adultstem cells is that there are a very small numberstem cells is that there are a very small number

of stem cells in each tissue. Stem cells areof stem cells in each tissue. Stem cells arethought to reside in a specific area of eachthought to reside in a specific area of eachtissue where they may remain quiescent (nontissue where they may remain quiescent (non--dividing) for many years until they are activateddividing) for many years until they are activatedby disease or tissue injury.by disease or tissue injury.

nn The adult tissues reported to contain stem cellsThe adult tissues reported to contain stem cellsinclude brain, bone marrow, peripheral blood,include brain, bone marrow, peripheral blood,blood vessels, skeletal muscle, skin and liver.blood vessels, skeletal muscle, skin and liver.


13/30

nn Scientists in many laboratories are trying to findScientists in many laboratories are trying to find

ways to grow adult stem cells inways to grow adult stem cells in cell culturecell culture andand

manipulate them to generate specific cell typesmanipulate them to generate specific cell types

so they can be used to treat injury or disease.so they can be used to treat injury or disease.nn Some examples of potential treatments includeSome examples of potential treatments include

replacing the dopaminereplacing the dopamine--producing cells in theproducing cells in the

brains of Parkinson's patients, developingbrains of Parkinson's patients, developing

insulininsulin--producing cells for type I diabetes andproducing cells for type I diabetes andrepairing damaged heart muscle following arepairing damaged heart muscle following a

heart attack with cardiac muscle cells.heart attack with cardiac muscle cells.


14/30

Embryonic stem cellsEmbryonic stem cells

nn Embryonic stem cellsEmbryonic stem cells::

nn derived from embryos.derived from embryos.

(Specifically, embryonic stem cells are derived(Specifically, embryonic stem cells are derived

from embryos that develop from eggs that havefrom embryos that develop from eggs that have

been fertilizedbeen fertilizedin vitroin vitroin anin anin vitroin vitrofertilizationfertilization

clinicclinicand then donated for research purposesand then donated for research purposes

with informed consent of the donors)with informed consent of the donors)They areThey are

not derived from eggs fertilized in anot derived from eggs fertilized in a

woman's body.woman's body.


15/30

nn TheThe embryosembryos from whichfrom which human embryonichuman embryonicstem cellsstem cells are derived are typically four or fiveare derived are typically four or five

days old and are a hollow microscopic ball ofdays old and are a hollow microscopic ball of

cells called thecells called the blastocystblastocyst..

nn The blastocyst includes three structures: theThe blastocyst includes three structures: thetrophoblasttrophoblast, which is the layer of cells that, which is the layer of cells that

surrounds the blastocyst thesurrounds the blastocyst the blastocoelblastocoel, which, which

is the hollow cavity inside the blastocyst andis the hollow cavity inside the blastocyst and

thethe inner cell massinner cell mass, which is a group of, which is a group ofapproximately 30 cells at one end of theapproximately 30 cells at one end of the

blastocoelblastocoel


16/30

Cultivating stem cellsCultivating stem cells

nn Growing cells in the laboratory is known asGrowing cells in the laboratory is known as cell culturecell culture..

nn Human embryonic stem cells are isolated by transferringHuman embryonic stem cells are isolated by transferringthethe inner cell massinner cell mass into a plastic laboratory culture dishinto a plastic laboratory culture dishthat contains a nutrient broth known asthat contains a nutrient broth known as culture mediumculture medium..

nn The cells divide and spread over the surface of the dish.The cells divide and spread over the surface of the dish.The inner surface of the culture dish is typically coatedThe inner surface of the culture dish is typically coatedwith mouse embryonic skin cells that have been treatedwith mouse embryonic skin cells that have been treatedso they will not divide. This coating layer of cells is calledso they will not divide. This coating layer of cells is calledaa feeder layerfeeder layer. The reason for having the mouse cells in. The reason for having the mouse cells in

the bottom of the culture dish is to give the inner cellthe bottom of the culture dish is to give the inner cellmass cells a sticky surface to which they can attach.mass cells a sticky surface to which they can attach.


17/30

nn Also, the feeder cells release nutrients into the culture Also, the feeder cells release nutrients into the culturemedium. Recently, scientists have begun to devise waysmedium. Recently, scientists have begun to devise waysof growing embryonic stem cells without the mouseof growing embryonic stem cells without the mousefeeder cells. This is a significant scientific advancementfeeder cells. This is a significant scientific advancement

because of the risk that viruses or other macromoleculesbecause of the risk that viruses or other macromoleculesin the mouse cells may be transmitted to the humanin the mouse cells may be transmitted to the humancells.cells.

nn Over the course of several days, the cells of the innerOver the course of several days, the cells of the innercell mass proliferate and begin to crowd the culture dish.cell mass proliferate and begin to crowd the culture dish.When this occurs, they are removed gently and platedWhen this occurs, they are removed gently and plated

into several fresh culture dishes.into several fresh culture dishes.nn The process of replating the cells is repeated many timesThe process of replating the cells is repeated many times

and for many months, and is calledand for many months, and is called subculturingsubculturing..


18/30

nn Each cycle of subculturing the cells is referred to as aEach cycle of subculturing the cells is referred to as apassagepassage. After six months or more, the original 30 cells. After six months or more, the original 30 cellsof the inner cell mass yield millions of embryonic stemof the inner cell mass yield millions of embryonic stemcells.cells.

nn Embryonic stem cells that have proliferated in cellEmbryonic stem cells that have proliferated in cellculture for six or more months without differentiating,culture for six or more months without differentiating,areare pluripotentpluripotent, and appear genetically normal are, and appear genetically normal arereferred to as anreferred to as an embryonic stem cell lineembryonic stem cell line..

nn Once cell lines are established, or even before thatOnce cell lines are established, or even before that

stage, batches of them can be frozen and shipped tostage, batches of them can be frozen and shipped toother laboratories for further culture andother laboratories for further culture andexperimentation.experimentation.


19/30

Tests used to identify Adult stemTests used to identify Adult stem

cellscellsnn (1) labeling the cells in a living tissue with molecular(1) labeling the cells in a living tissue with molecular

markers and then determining the specialized cell typesmarkers and then determining the specialized cell typesthey generatethey generate

nn (2) removing the cells from a living animal, labeling(2) removing the cells from a living animal, labelingthem in cell culture, and transplanting them back intothem in cell culture, and transplanting them back intoanother animal to determine whether the cellsanother animal to determine whether the cellsrepopulate their tissue of origin andrepopulate their tissue of origin and

nn (3) isolating the cells, growing them in cell culture, and(3) isolating the cells, growing them in cell culture, andmanipulating them, often by adding growth factors ormanipulating them, often by adding growth factors or

introducing newintroducing new genesgenes, to determine what differentiated, to determine what differentiatedcells types they can become.cells types they can become.


20/30

a single adult stem cell should be able to generate a linea single adult stem cell should be able to generate a lineof genetically identical cellsof genetically identical cellsknown as aknown as a cloneclonewhichwhichthen gives rise to all the appropriate differentiated cellthen gives rise to all the appropriate differentiated celltypes of the tissue.types of the tissue.

Scientists tend to show either that a stem cell can giveScientists tend to show either that a stem cell can give

rise to a clone of cells in cell culture, or that a purifiedrise to a clone of cells in cell culture, or that a purifiedpopulation of candidate stem cells can repopulate thepopulation of candidate stem cells can repopulate thetissue after transplant into an animal.tissue after transplant into an animal.

Recently, by infecting adult stem cells with a virus thatRecently, by infecting adult stem cells with a virus that

gives a unique identifier to each individual cell, scientistsgives a unique identifier to each individual cell, scientistshave been able to demonstrate that individual adulthave been able to demonstrate that individual adultstem cell clones have the ability to repopulate injuredstem cell clones have the ability to repopulate injuredtissues in a living animal.tissues in a living animal.


21/30

Hematopoietic and stromal stemHematopoietic and stromal stem

cell differentiationcell differentiation


22/30

scientists have reported that adult stemscientists have reported that adult stem

cells occur in many tissues and that theycells occur in many tissues and that they

enter normalenter normal

differentiationdifferentiation

pathways topathways to

form the specialized cell types of theform the specialized cell types of the

tissue in which they reside. Adult stemtissue in which they reside. Adult stem

cells may also exhibit the ability to formcells may also exhibit the ability to form

specialized cell types of other tissues,specialized cell types of other tissues,which is known aswhich is known astransdifferentiationtransdifferentiation

ororplasticityplasticity


23/30

nnThe most important potential applicationThe most important potential applicationof human stem cells is the generation ofof human stem cells is the generation ofcells and tissues that could be used forcells and tissues that could be used for

cellcell--based therapiesbased therapies..nnToday, donated organs and tissues areToday, donated organs and tissues are

often used to replace ailing or destroyedoften used to replace ailing or destroyedtissue, but the need for transplantabletissue, but the need for transplantabletissues and organs far outweighs thetissues and organs far outweighs theavailable supply.available supply.


24/30

nnStem cells, directed to differentiate intoStem cells, directed to differentiate into

specific cell types, offer the possibility of aspecific cell types, offer the possibility of a

renewable source of replacement cells andrenewable source of replacement cells and

tissues to treat diseases includingtissues to treat diseases including

Parkinson's and Alzheimer's diseases,Parkinson's and Alzheimer's diseases,

spinal cord injury, stroke, burns, heartspinal cord injury, stroke, burns, heart

disease, diabetes, osteoarthritis, anddisease, diabetes, osteoarthritis, andrheumatoid arthritis.rheumatoid arthritis.


25/30


26/30

Autologous Hematopoetic Stem Cell Autologous Hematopoetic Stem Cell

Transplantation in NewlyTransplantation in NewlyDiagnosed Type I Diabetes MellitusDiagnosed Type I Diabetes Mellitus

Journal of American Medical Association,Journal of American Medical Association,

April 11, 2007 April 11, 2007

Author: Julio C. Voltarelli, MD, PhD, et al. Author: Julio C. Voltarelli, MD, PhD, et al.


27/30

Objective: To determine the safety andObjective: To determine the safety and

metabolic effects of high dosemetabolic effects of high dose

immunosuppression followed byimmunosuppression followed by

autologous hematopoeitic stem cellautologous hematopoeitic stem cell

transplantation in newly diagnosed type Itransplantation in newly diagnosed type I

DM.DM.


28/30

Setting and Participants:Setting and Participants:

nnBone Marrow Transplantation Unit of theBone Marrow Transplantation Unit of theSchool of Medicine of Ribeirao Preto, BrazilSchool of Medicine of Ribeirao Preto, Brazil

nn15 patients with type I DM, aged 1415 patients with type I DM, aged 14--3131

years oldyears old


29/30

ResultsResults

nn14 patients became insulin14 patients became insulin--free (1 for 35free (1 for 35

months, 4 for at least 21 months, 7 for atmonths, 4 for at least 21 months, 7 for atleast 6 months and two with late responseleast 6 months and two with late response

were insulinwere insulin--free for 1 and 5 months,free for 1 and 5 months,

respectively).respectively).

nn1 patient resumed insulin use 1 year after1 patient resumed insulin use 1 year afterAHSTAHST


30/30

ConclusionConclusion

nnHigh dose immunosuppression and AHSTHigh dose immunosuppression and AHSTwere performed with acceptable toxicity inwere performed with acceptable toxicity ina small number of patients with newlya small number of patients with newlydiagnosed Type I DM. With AHST, betadiagnosed Type I DM. With AHST, betacell function was increased in all but 1cell function was increased in all but 1patient and induced prolonged insulinpatient and induced prolonged insulinindependence in the majority of theindependence in the majority of thepatientspatients

Documents

STEMCELL TRANSPLANTATIO