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Transcript
Stem Cells:
Scientific Potential
and Alternatives
Glenn Sauer, Ph.D.
Biology Department
Fairfield University
Scientific
Principles
What are stem cells?
 How are they used?
 What is the potential
for therapeutic
applications?


More information:
 www.nih.gov
Review of Terminology
DNA - deoxyribonucleic acid, makes up genes
 Gene - functional unit of heredity, a segment of
DNA located at a specific site on a chromosome;
genes direct the formation of proteins.
 Nucleus - a membrane bound structure in the cell
which contains the chromosomes.
 Cell - the basic unit of life, all living organisms are
made up of cells



somatic cell - a cell of the body (220 types in humans)
germ cell - an egg or sperm
Differentiation of Human Tissues
Early embryonic
cells unspecialized
 Three primary
tissue layers:





Ectoderm
Mesoderm
Endoderm
All tissues develop
from here
Adult Stem Cells
Stem cells = cells that have
the ability to divide for
indefinite periods and give
rise to specialized cells
Progenitor cells = partially
specialized cells that can
give rise to particular cell
types
Stem Cells of the Bone Marrow
The Problem of Cell Potency
Unipotent - cell divides to produce same cell type;
most cells
 Multipotent - can give rise to some cell types; adult
stem cells
 Pluripotent - able to give rise to most cell types;
embryonic, very small number of adult stem cells
 Totipotent - unlimited cabability; can give rise to all
cell types; only in early embryos

Early Embryological Development
Derivation of Human Pluripotent
Stem Cells
John Gearhart (1998) - embryonic germ (EG) cells
cultured from gonadal ridge of 5- to 9-week old
fetal tissue obtained from elective abortions.
Proc. Natl. Acad. Sci. USA 95: 13726-13731.
 James Thomson (1998) - embryonic stem (ES)
cells derived from inner cell mass of blastocysts
created through in vitro fertilization procedures
and donated for research purposes.
Science 282: 1145-1147.

Derivation of hES Cells
“Excess” frozen blastocysts
donated from fertility clinics
 Inner cell mass (embryo)
separated from trophoblast
(placenta)
 Cells dissociated and cultured
in laboratory
 Can be made to differentiate
using chemical signals

Applications of Pluripotent Stem Cells

Basic research in human development


Drug development


“decision-making genes” (birth defects, cancer)
human cell lines for all cell types
Cell therapies

replacement tissue for degenerative conditions
(Parkinson’s and Alzheimer’s disease, diabetes,
heart disease, stroke, arthritis)
Example: Diabetes
Insufficient insulin
production in pancreas
 Insulin needed for
glucose uptake
 “Islet-like” cells derived
from stem cells
produce insulin
 Eliminates need for
insulin injections

Scientific Challenges Remaining
Understanding of cellular events that
lead to differentiation and specialization
 Immunologic rejection - Can stem cells
be modified to minimize tissue
incompatibility?
 Time of development and expense of
treatments

Rejection: Possible Solutions
Genetic
engineering
 Somatic cell
nuclear transfer
(SCNT)


develops into a
blastocyst


Dolly the sheep
cloning (banned
by Congress)
The Controversy

Tremendous potential
scientific community
 medical profession
 patient advocates


Religious/ethical
conflict
human dignity
 abortion issue

When does “Human” Life Begin?
Genetic view - at conception (fertilization)
 Embryologic view - after 14 days when each
embryo can produce only one individual
 Mental activity view - after 25 weeks when
the human-specific EEG can be measured
(death is defined as the loss of EEG)
 Birthday view - life begins when infant is
“metabolically” independent of mother

The Bush Decision - Aug 9, 2001
“We must proceed with great care” - limited
approval for ongoing research.
Fully funded: adult stem cells, umbilical cord
 Restricted: embryonic (existing cell lines only)



64 existing lines
 20 in United States
 Sweden, India, Australia, Israel
Unfunded: new donor embryos, cloned embryos
Total federal funding for 2001:
$ 250 M
Reaction to Bush Decision

Scientists




Conservative Christians



some $$ better than none
64 cell lines not enough
concerns about control
relief that more research is
not allowed
broken campaign promise
Patient Advocates


cautious optimism
emotional pleas for more $$
Religions Ponder the Issue
Roman Catholic, Evangelical Christians opposed since stem cells are derived from
the destruction of embryos
 Most groups do not have official positions
 Most common positions:

Judaism - supportive since it serves a common
good (fighting disease)
 Muslim - abortion is wrong but life begins when
fertilized egg touches womb
 Presbyterian, UCC - “generally supportive”

State Response
California voters approve Proposition 71
which provides $3 Billion for stem cell
research (2004)
 Other states approve similar measures

(Connecticut, Florida, Illinois, Massachusetts,
Missouri, New Hampshire, New York,
Pennsylvania, Texas, Washington, Wisconsin)
Stem Cell Research Enhancement Act

Would allow use of surplus in vitro fertilization
embryos with donor permission (2005)



Passed House of Representatives (238-194) and
Senate (63-37)
Vetoed by George Bush (2006)
Stem Cell Therapeutic and Research Act of
2005 (enacted)

Provides funds for adult stem cell therapies and
umbilical cord stem cells
Current Situation
Barack Obama executive order allows
research with new stem cell lines (2009)
 BUT Dickey Amendment to 1995
Appropriations Bill bans funds for human
cloning or any research that voluntarily
destroys embryos.
 RESULT  Research Labs using state
funds to create stem cell lines and federal
funds to work with the cells

Alternatives to hES Cells

Umbilical cord blood
Contains hematopoietic and mesenchymal
stem cells (lower potency than hES)
 Patient specific
 Cord blood banks

$2000 collection and $125/year storage fees
 Some public banks for donated cells

Alternatives to hES Cells

Induced Pluripotent Stem Cells (iPS)
Alternatives to hES Cells

Induced Pluripotent Stem Cells (iPS)
Uses Oct4, Sox2, Klf4 and c-Myc genes
 Show higher potency than cord cells
 Low efficiency (recent improvements)
 Other problems

Abnormal aging
 Tumor production
 Incomplete reprogramming

Alternatives to hES Cells

Direct Cell Reprogramming - 2011

Turns one cell directly into another

(ex. Skin cell  Neuron)
Uses mRNA, no viral vector
 Eliminates need for stem cells
 Potential and problems are uncertain

Autologous Stem Cell Therapies
Self-donation of mesenchymal stem cells
 Injected (with or without chemical
treatment) into injury site
 Not FDA approved

Clinical trials underway (heart attack, spinal
cord injury, etc.)
 Many Americans seek overseas options

No proven effectiveness
 Costly
 High pressure sales tactics

Questions?



The United States has been criticized by some for being too
restrictive to stem cell-based research and therapies.
Should U.S. laws be relaxed to be more accommodating to
those wishing treatment?
A recent study by Duke University predicted that by the year
2050, regenerative procedures based on stem cell and other
biotechnologies could extend an average human life span by
up to 100 years. Is this a desirable goal?
Many biotechnologies are vastly expensive, yet much of the
basic research supporting these developments is paid for by
taxpayers. Who should benefit?