Download adult stem cells

The Living World
Fifth Edition
George B. Johnson
Jonathan B. Losos
Chapter 16
The Revolution in Cell Technology
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
16.1 Proving That Reproductive
Cloning is Possible
• Hans Spemann proposed in 1938 that cloning might be
possible by removing the nucleus from an egg cell and
replacing with a nucleus from another cell
• early attempts in cloning were unsuccessful unless the
transplanted nucleus was from a very early stage of
development
• the theory of irreversible determination suggested that
animal cells become irreversibly committed after the first
cell divisions
Figure 16.1 A cloning experiment.
16.1 Proving That Reproductive
Cloning is Possible
• geneticists working in Scotland made a key
breakthrough in animal cloning
 Keith Campbell suggested they conduct nuclear
transfers between a donor and recipient cell that were
at identical stages of the cell cycle
 the cells were starved so that they were at the
beginning of the cell cycle at the G1 checkpoint
 Neil First in 1994 and Campbell and Ian Wilmut in
1995 successfully cloned farm animals from
advanced embryos using this method
16.1 Proving That Reproductive
Cloning is Possible
• Wilmut progressed with the method to transfer
successfully a nucleus from an adult cell into an
enucleated egg
 Wilmut used an adult sheep’s mammary gland as the nuclear
donor
 both the donor mammary cells and the enucleated eggs were
first starved and a brief electrical shock allowed the contents to
fuse together
 the resulting embryos developed into blastulae and were
implanted into a surrogate mother
 “Dolly” the cloned lamb was born on July 5, 1996
Figure 16.2 Wilmut’s animal cloning
experiment.
Figure 16.3 A parade of cloned
critters.
16.3 Problems with Reproductive
Cloning
• many problems have been encountered with
reproductive cloning since Dolly
 most transplanted cloned embryos die late in
pregnancy
• large offspring syndrome describes the oversized condition
of many of these transplants
 among surviving cloned offspring, their development
into adults goes unexpectedly haywire
• most do not survive to live a normal life span
• for example, Dolly died prematurely in 2002
16.3 Problems with Reproductive
Cloning
• reprogramming by parent males and females of
the sperm and eggs may affect cloning success
 genomic imprinting involves chemical changes to
DNA that alters when genes are expressed without
changing the sequences
• genes can be locked on or off
• normal animal development depends on precise genomic
imprinting
16.3 Problems with Reproductive
Cloning
• genomic imprinting occurs at different stages
 gametic imprinting
• takes place in adult reproductive tissue
• requires months for sperm and years for eggs
 zygotic imprinting
• the egg cell cytoplasm acts to reprogram the DNA introduced
by the sperm
• donor DNA to be cloned may be less efficient at doing this
reprogramming
Figure 16.4 Two forms of genomic
imprinting.
16.4 Embryonic Stem Cells
• embryonic stem cells are totipotent
 this means that they have the ability to form
any body tissue, and even an adult animal
• later in development the embryonic stem
cells differentiate into adult stem cells
 these cells produce only one kind of tissue
 the genes needed to produce other types of
tissues are turned off
Figure 16.5 Human embryonic
stem cells (x20).
16.4 Embryonic Stem Cells
• embryonic stem cells offer the possibility
of restoring damaged tissues
 embryonic stem cells grown in culture could
be induced to form any type of tissue in the
body
 this healthy tissue can be injected into a
patient where it will grow and replace
damaged tissue
Figure 16.6 Using embryonic stem
cells to restore damaged tissue.
16.5 Therapeutic Cloning
• the possibility for immune rejection of transplanted stem cells must
be addressed in order to make stem cell therapy work
• in therapeutic cloning, DNA from adult cells are used to create an
embryo from an individual
 stem cells are then harvested from the embryo, which is subsequently
destroyed
 the tissue developed from these stem cells can be injected into the
damaged host
 there is no issue of immunological tolerance because the donor and
recipient of the stem cell therapy are the same individual
Figure 16.8 How human embryos might
be used for therapeutic cloning.
16.6 Grappling with the Ethics of
Stem Cell Research
• the use of embryonic stem cells raises a number
of important ethical concerns, including
 should human embryos be destroyed?
 how can the potential for future abuse be avoided?
 are there alternative sources to using embryonic stem
cells?
16.7 Initial Attempts at Gene
Therapy
• gene transfer therapy involves
transferring healthy versions of a gene into
cells that lack them
 while the research is promising, problems
remain in finding an appropriate vector for
gene transfer
• adenovirus vector was used to piggyback healthy
genes but was both subject to immune attack and
prone to introduce mutations that lead to cancer
Figure 16.7 Initial Attempts at Gene
Therapy.
16.8 More Promising Vectors
• adeno-associated virus (AAV) is a more
promising choice for vector
 this parvovirus needs adenovirus to replicate
but is a good gene carrier once its two genes
are removed
 it infects easily but, when the AAV genes are
removed, does not produce an immune
response or introduce cancerous mutations
Figure 16.10 Using gene therapy to cure a
retinal degenerative disease in dogs.
16.9 Ethical Issues Raised by
Gene Therapy
• ethicists prefer the term gene intervention in
lieu of gene therapy to describe any procedure
that deliberately alters a person’s genes
• it is important to consider the permanence of
these changes
 changes to somatic tissue are not inherited
 changes to germ-line tissues are inherited
16.9 Ethical Issues Raised by
Gene Therapy
• beneficence principle
 ethicists use this to weigh the risks versus the
benefits when making decisions about
potential therapy
• respect-for-persons principle
 ethicists respect the right of persons affected
by the procedure to make their own informed
decisions
Inquiry & Analysis
• Judging by visual
similarity, which adult
dog is the closer
relative of Snuppy?
• What evidence would
you accept that
Snuppy is indeed a
clone?
Photo of Snuppy, with his Clone
Dad and Surrogate Mom