stem cell therapy: what a

Stem cell therapy: what a cardiologist needs to know

Robert Roberts MDChief of CardiologyBaylor College of MedicineHouston, Texas

Piero Anversa MDDirector, Cardiovascular Research InstituteNew York Medical College Valhalla, New York

Seigo Izumo MDProfessor of MedicineHarvard Medical SchoolBoston, Massachusetts

Stem cell therapyThe basics

stem cells

are primitive cells

can renew themselves

can develop into different cell types

have the potential to become more differentiated cells

in vitro fertilized embryo

multiple embryos produced in vitrofor clinical purposes

donated surplus embryos used to culture embryonic stem cells

Source: University of Wisconsin

Stem cell therapyEmbryonic stem cells

derived from the early embryo

are totipotent (can differentiate into all cell types of all organs)

used to create gene knockout (KO) animal models for CVD study

KO mouse (©Taconic)

Stem cell therapy Adult stem cells

reside in adult tissue

are multipotent (differentiating capacity is more limited)

satellite cells in skeletal muscle regenerate muscle after injury

stem cells in bone marrow replenish blood cells and have potential to become cardiovascular cells

number of cells in the human body: 200 trillion

number of unique cell types all derived from an estimated 20–30 stem cells: 200

Stem cell therapyBody cells

plasticity of adult stem cells much greater than suspected

shown to generate cell lineages different from the organ they reside in

Stem cell therapy Plasticity

adult hematopoietic stem cells show potential to regenerate myocardium — both myocytes and coronary vessels

injection of this cell in the region bordering infarct in mice improved ventricle function

embryonic stem cells shown in vitro to differentiate into cardiomyocytes

Stem cell therapyNew myocardium

Orlic D, et al. Nature 2001;410(6829):701-705Kocher AA, et al. Nat Med 2001;7(4):430-436

“It is very clear that at this early stage there are some promising signs that some of the adult stem cells may in fact be able to turn into other cells with appropriate stimulation. Whether these cells will really become true functioning liver or brain cells on their own when they are put into a human being remains to be determined.”

Stem cell therapyPromising signs


Embryonic stem cells

can form any 1 of the 200 different cell types

obtained from 2 sources miscarried/aborted fetus unused fetus from in vitro fertilization

Adult stem cells

have a potential and have been successfully used in the treatment of leukemia

Stem cell therapySummary

different from stem cell research

prohibited in the US but approved in the UK

nucleus is taken out of one cell and transplanted into another

recipient cell then adopts the identity of the donor

Stem cell therapyCloning by nuclear transfer

Dolly, cloned by nuclear transfer(©Roslin Institute)

Stem cell therapyApplications of stem cells


“This is very early in the game, and if we had as many embryonic stem cells as we wanted tomorrow, there is a lot of research to be done in terms of what are the appropriate stimuli, what could turn these cells into liver or heart cells. Discovering what the particular stimuli are may take 2 or 3 years, even if stem cell research is approved and stem cells become available from embryonic form.”

embryonic stem cells could be used to grow cardiomyocites in vitro to be transplanted into MI patients

adult stem cells could generate cardiomyocytes in culture, or could be injected directly into the MI animal

cells home to area of damage and generate new myocardium, including electrically coupled myocytes and coronary arterials and vessels

Stem cell therapyCardiomyocytes

Piero Anversa MDDirector, Cardiovascular Research InstituteNew York Medical CollegeValhalla, New York

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“I think that there is a potential in the adult stem cell…. Bone marrow-derived stem cells have the capacity to go to areas of damage in the myocardium and generate new myocardium, composed of myocytes and vessels.”

Stem cell therapyA potential


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embryonic stem cells used as in vitro model

to study cardiac growth

to investigate adverse effects of drugs on cardiac development

Stem cell therapyIn vitro

“I think that it is actually good to have this controversy…this is a central issue that we cannot avoid.”



Stem cell therapyEthical debate

“It was always intended by the NIH that, if this research is going to be funded, a set of rules has to be established for investigators to follow.”


Stem cell therapyAdult stem cell research


“The question is, can we get what we want by just funding research in the adult stem cell?”

“There will be little ethical issue for the use of adult stem cells, in my opinion, particularly concerning those coming from bone marrow.”

how many adult stem cells lie in what organ is still unclear

how to locate adult stem cells in the heart is still unknown

more needs to be known about the characteristics of the cell surface

answers may lie in the study of embryonic stem cells

Stem cell therapyLocation


“We haven’t done any type of research to identify whether there are stem cells in the heart like there have found in the brain. I think the issue is more complex than just analyzing, identifying, characterizing, and understanding the biology of embryonic stem cells. We need to also look for stem cells in other organs which we always thought were not present. We might be surprised again, like we were a couple of years ago when we found out that neural stem cells do exist.”

Stem cell therapyComplex issue


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how to search for the adult stem cell begin with markers used to isolate hematopoietic

primitive bone marrow cells(c-kit, sca-1, mdr-1 etc)

several approaches can be used initially to see whether there is a population of primitive undifferentiated cells in the heart or the kidney, to see whether there is a potential for regeneration in these organs, and to try to interfere with disease processes

Stem cell therapySearch for stem cells


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until recently, the heart was assumed to be terminally differentiated

no previous search for stem cells

“Certainly that’s a line of research that should be pursued, and it is already showing some promising results.”

Stem cell therapyThe heart


study of stem cells in mice and other species may help identify human adult stem cells

taking advantage of evolutionary conservation in development, one can probably identify a number of markers for adult stem cells

“The availability of human stem cells will probably hasten the research.”

Stem cell therapyThe future


Stem cell therapyConclusions

many fundamental uses for stem cells

great potential for both embryonic and adult stem cell fields

every effort should be made to pursue adult stem cells, regardless of what the future holds for embryonic stem cell research

research with embryonic stem cells needs to be properly debated and formulated


stem cell therapy: what a

Technology

injury stem cells

basics stem cells

stem cell therapy body

stem cell therapy plasticity

plasticity of adult

fertilization adult

adult hematopoietic

embryonic stem cells