Stem Cell Therapy in Asthma

8/14/2019 Stem Cell Therapy in Asthma

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Fawzia aboaliProf. of allergy &immunology

Ain shams faculty of medicine


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Stem CellsStem Cells :: What are Stem Cells?What are Stem Cells?

Stem cells are unspecialized cellsStem cells are unspecialized cellscapable of multiplying and formingcapable of multiplying and formingmany different kinds of tissuemany different kinds of tissue

through cellular generation andthrough cellular generation anddifferentiation.differentiation.


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STEM CELLS HAVE 3 BASICSTEM CELLS HAVE 3 BASIC

PROPERTIESPROPERTIES

11 22

33

D1 D2........ D

n

CAPABLE OFCAPABLE OF

SELF-RENEWALSELF-RENEWAL

UNDIFFERENTIATEDUNDIFFERENTIATED

AND ABLE TO DIVIDEAND ABLE TO DIVIDE

INDEFINITELYINDEFINITELY

CAPABLE OF DIFFERENTIATION INTOCAPABLE OF DIFFERENTIATION INTO

DIFFERENT CELL TYPESDIFFERENT CELL TYPES

Adapted from Caltech 2000Adapted from Caltech 2000


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Where are stem cells found?1. Embryos (ESC)2. Adult Stem Cells (ASC)...


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Embryonic Stem Cells (ESCs)Embryonic Stem Cells (ESCs)

August 9, 2001 - President Bush restricted

federal funding of human embryonic stemcell research .

Science and Politics of ESCsresearch


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Former First Lady NancyFormer First Lady NancyReagan has been privatelyReagan has been privatelylobbying in favour of federallobbying in favour of federalfinancing for embryonicfinancing for embryonicstem cell research.stem cell research.

Mrs Reagan is said to believeMrs Reagan is said to believe

that the research could leadthat the research could leadto a cure for Alzheimer'sto a cure for Alzheimer'sdisease, which has afflicteddisease, which has afflicted

her husband, former USher husband, former USPresident Ronald Reagan.President Ronald Reagan.


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2001 .3/2009/ 9

President Barack Obama announced

Monday that he will allow federal financing

of medical research using stem cells from

discarded human embryos,March,8,2009


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Adult Stem Cells (ASC)

Umbilical Cords Adult tissue such as: neural (brain)

blood

adipose (fat) nose (olfactory cells) bone marrow

mammary gland


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STEM CELL THERAPIES TODAYSTEM CELL THERAPIES TODAY

These include:These include: Adult Stem Cell Transplant: Bone MarrowAdult Stem Cell Transplant: Bone Marrow

Stem CellsStem Cells

Adult Stem Cell Transplant: PeripheralAdult Stem Cell Transplant: PeripheralBlood Stem CellsBlood Stem Cells

Umbilical Cord Blood Stem CellUmbilical Cord Blood Stem Cell

TransplantTransplant


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What is stem cell transplant?What is stem cell transplant?

A stem cell transplant is the infusionA stem cell transplant is the infusionof healthy cells to replace orof healthy cells to replace orregenerate diseased or damaged ones.regenerate diseased or damaged ones.


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Asthma & COPDAsthma & COPD


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Allergies and respiratory conditions suchAllergies and respiratory conditions such

as asthma &COPD are a prevalentas asthma &COPD are a prevalentproblem allover the world.problem allover the world.

In children these problems are especiallyIn children these problems are especially

destructive. Their small, developingdestructive. Their small, developingbodies aren't always strong enough tobodies aren't always strong enough todeal with the damage caused by allergiesdeal with the damage caused by allergies

Stem cell transplant provides hopes forStem cell transplant provides hopes forthose ,and for cases with severe COPD.those ,and for cases with severe COPD.


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Stem cells can be helpful through,Stem cells can be helpful through,ridding the body of allergiesridding the body of allergies and at theand at the

same time ,same time ,repair lung injury.repair lung injury.


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How can stem cell therapies treatHow can stem cell therapies treat

allergies?allergies? Stem cells are the building blocks for everyStem cells are the building blocks for every

cell in the body.cell in the body.

Stem cell transplants are a kind ofStem cell transplants are a kind ofimmune therapy that transfers cells insteadimmune therapy that transfers cells insteadof antibodies.of antibodies.

Recent studies showed markedRecent studies showed markedimprovement of allergy after marrowimprovement of allergy after marrowtransplantstransplants


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Healthy stem cells are transplanted to theHealthy stem cells are transplanted to the

affected areas of the body-in this case, theaffected areas of the body-in this case, theimmune system.immune system.

Once there, they receive messages fromOnce there, they receive messages from

the cells around them and begin to takethe cells around them and begin to takeon the function of those cells (T&B cells).on the function of those cells (T&B cells). They literally become immune systemThey literally become immune system

cells.cells. They are designed to heal and rebuild,They are designed to heal and rebuild,

and they strengthen the immune systemand they strengthen the immune system

through regeneration.through regeneration.


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They do this by mimicking the functionThey do this by mimicking the functionof whatever cells they're sent to heal andof whatever cells they're sent to heal and

create newer, healthier cells that performcreate newer, healthier cells that performproperly.properly.

the discovery of blood stem cells in bonethe discovery of blood stem cells in bonemarrow revealed the secret of rebuildingmarrow revealed the secret of rebuildingthe immune system via bone marrowthe immune system via bone marrow

transplants.transplants.


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Technique:Technique:

After stem cells derived from umbilicalAfter stem cells derived from umbilical

cord blood, injected into the patientscord blood, injected into the patientsblood, they migrate to the bone marrow,blood, they migrate to the bone marrow,where they mature into blood cells,where they mature into blood cells,

including all the different cells of theincluding all the different cells of theimmune system.immune system.

This is a complex process involving, theThis is a complex process involving, the

action of cytokines, which regulatesaction of cytokines, which regulatesdistinct steps in the life of stem cells anddistinct steps in the life of stem cells andtheir immune descendents.their immune descendents.


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Repair of lung injuryRepair of lung injury


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Stem cell therapy to repair lung injury:Stem cell therapy to repair lung injury:

asthma & COPD are responsible for lungasthma & COPD are responsible for lunginjuries and airway remodeling which areinjuries and airway remodeling which are

leading causes of morbidity and mortalityleading causes of morbidity and mortality

worldwide.worldwide. The use of adultThe use of adult stemstemcellcells to help withs to help with

lung regeneration andlung regeneration and

repair could be arepair could be anewer technology in clinical andnewer technology in clinical andregenerativeregenerativemedicine.medicine.


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NormalNormal repair of the airway involvesrepair of the airway involvesregeneration of the airway epitheliumregeneration of the airway epitheliumby stem cells in both the proximalby stem cells in both the proximalairway and distal airspace, whereasairway and distal airspace, whereasaberrant repair may result from stemaberrant repair may result from stemcells that lead to fibrosis and airwaycells that lead to fibrosis and airwayremodeling.remodeling.


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These stem cells are resident in specificThese stem cells are resident in specificprotected niches in the lung, or they canprotected niches in the lung, or they canbe mobilized from the bone marrow andbe mobilized from the bone marrow andrecruited from the circulation in therecruited from the circulation in thesetting of severe injury.setting of severe injury.

Stem cell transplant technology , couldStem cell transplant technology , couldovercome the problem of aberrant repair.overcome the problem of aberrant repair.


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Technique:Technique: stem cells are grown in culture withstem cells are grown in culture with

special nutrients and growth factors tospecial nutrients and growth factors toprogram them to become pulmonary stemprogram them to become pulmonary stemcells.cells.

This culture method usually requiresThis culture method usually requiresabout three weeks in time.about three weeks in time. Patients are given progenitor cells,Patients are given progenitor cells,

pulmonary stem cells and human stem cellpulmonary stem cells and human stem cellgrowth factors intravenously.growth factors intravenously.


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Post stem therapy program medicationsPost stem therapy program medicationsare then given to the patient to be takenare then given to the patient to be taken

for six months.for six months. In a recent study, 3 male patients sufferingIn a recent study, 3 male patients suffering

from severe chronic obstructivefrom severe chronic obstructive

pulmonary disease (COPD) werepulmonary disease (COPD) weresubmitted to autologous adult stem cellsubmitted to autologous adult stem cellimplant . After 30 days of the procedureimplant . After 30 days of the procedure

all the patients showed improvedall the patients showed improvedpulmonary functions.pulmonary functions.


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Sources of Stem Cells for Lung Repair,Sources of Stem Cells for Lung Repair,

Regeneration, and RemodelingRegeneration, and Remodeling

n Endogenous Lung Stem CellsEndogenous Lung Stem Cells

ProgenitorProgenitor cellcells that participate in the maintenances that participate in the maintenance

and repairand repairof injuredof injured lunglungepithelium have beenepithelium have beendescribed for tracheobronchial,described for tracheobronchial,bronchiolar, andbronchiolar, andalveolar compartments .alveolar compartments .

n Specialized Cells Derived from Embryonic andSpecialized Cells Derived from Embryonic andadult Stem Cellsadult Stem CellsDifferentiating cultures of embryonic &adult stemDifferentiating cultures of embryonic &adult stemcells have been proposedcells have been proposedas an alternative source ofas an alternative source of

lung stemlung stem

cells.cells.

F t N d d A ti i t d Diffi ltiFuture Needs and Antici

pated Difficulties


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Future Needs and Anticipated DifficultiesFuture Needs and Anticipated Difficulties How are stem cells maintained within the lung?How are stem cells maintained within the lung?

How is the stem cell impacted by changes inHow is the stem cell impacted by changes in

the cytokine andthe cytokine andgrowth factor condition of the chronically diseasedgrowth factor condition of the chronically diseased lung?lung?

Basic studies areBasic studies areneeded to develop and optimize methods forneeded to develop and optimize methods for

the isolation, purification and validation of lung stem cells.the isolation, purification and validation of lung stem cells.

How might cell-based therapeutic interventions beHow might cell-based therapeutic interventions beconsideredconsideredin light of known differences between airwayin light of known differences between airway

regions &region-specific stemregions &region-specific stemcells?cells?

How might the beneficial effects of engraftingHow might the beneficial effects of engraftingcells becells becontroledcontroledwhile avoiding the potential harmful effects?while avoiding the potential harmful effects?


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Therefore, lungTherefore, lung stemstemcellcell biology maybiology mayprovide novel approachesprovide novel approachesto therapy andto therapy andcould represent a great promise for thecould represent a great promise for thefuturefutureof molecular medicine. In fact,of molecular medicine. In fact,several diseases can be slowedseveral diseases can be slowedor evenor evenblocked byblocked by stemstemcellcell transplantation.transplantation.

R fR f


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References:References:

n Brigitte N. GompertsBrigitte N. Gomperts11 and Robert M. Strieterand Robert M. Strieter::: Stem Cells: Stem Cells

and Chronic Lung Disease :Annual Review of Medicine,2007and Chronic Lung Disease :Annual Review of Medicine,2007Vol. 58: 285-298,Vol. 58: 285-298,

n LoebingerMRLoebingerMR,,AguilarSAguilarS,,JanesSMJanesSMTherapeutic potential ofTherapeutic potential ofstem cells in lung disease: progress and pitfalls.stem cells in lung disease: progress and pitfalls. Clin SciClin Sci

(Lond). 2008 Jan;114(2):99-108.(Lond). 2008 Jan;114(2):99-108.

n Dario Siniscalco,Review: Stem cell therapy: the greatDario Siniscalco,Review: Stem cell therapy: the great

promise in lung disease,promise in lung disease, Therapeutic Advances inTherapeutic Advances in

Respiratory Disease, (2008) Vol. 2, No. 3, 173-177Respiratory Disease, (2008) Vol. 2, No. 3, 173-177n Isabel P NeuringerIsabel P Neuringer11 andand Scott H RandellScott H Randell22 Stem cells andStem cells and

repair of lung injuriesrepair of lung injuries Respiratory ResearchRespiratory Research 2004,2004, 5:5:66

PICASS
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Loebinger%20MR%22[Author]&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlushttp://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Loebinger%20MR%22[Author]&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlushttp://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Aguilar%20S%22[Author]&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlushttp://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Aguilar%20S%22[Author]&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlushttp://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Janes%20SM%22[Author]&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlushttp://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Janes%20SM%22[Author]&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlushttp://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Janes%20SM%22[Author]&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlushttp://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Janes%20SM%22[Author]&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlushttp://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Janes%20SM%22[Author]&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlushttp://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Aguilar%20S%22[Author]&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlushttp://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Loebinger%20MR%22[Author]&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus


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Stem Cell Therapy in Asthma