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Unit 3

Cell Renewal
Stem Cell and its characteristics

●Most fully differentiated cells in adult animals, however, are no longer


capable of cell division. Nonetheless, they can be replaced by the proliferation of a
subpopulation of less differentiated self-renewing cells called
stem cells
●Because they retain the
capacity to proliferate and replace differentiated cells throughout the lifetime of an animal,
stem cells play a critical role in the maintenance of most
tissues and organs.
●The key property of stem cells is that they divide to produce one daughter
cell that remains a stem cell and one that divides and differentiates (Figure
19.5). Stem cells typically give rise to rapidly proliferating cells (called transitamplifying cells)
that undergo several divisions before they differentiate,
so division of a stem cell leads to the production of multiple differentiated
cells
●Stem cells were first identified in the hematopoietic (blood-forming)
system by Ernest McCulloch and James Till in 1961 in experiments showing that single cells
derived from mouse bone marrow could proliferate
and give rise to multiple differentiated types of blood cells

All
these cells have limited life spans ranging from less than a day to a few
months, and all are derived from the same population of hematopoietic
stem cells. More than 100 billion blood cells are lost every day in humans,
and must be continually produced from hematopoietic stem cells in the bone marrow (Figure
19.6). Descendants of the hematopoietic stem cell
continue to proliferate and undergo several rounds of division as they
become committed to specific differentiation pathways, as determined
by growth factors that direct cell differentiation. Once they become fully
differentiated, blood cells cease proliferation, so the maintenance of differentiated blood cell
populations is dependent on continual division of
the self-renewing hematopoietic stem cell.

The intestine provides an excellent example of stem cells in the self-renewal


of an epithelial tissue. The intestine is lined by a single layer of epithelial cells
that are responsible for the digestion of food and absorption of nutrients

Stem cells are also responsible for continuous renewal of the skin and hair.
Like the lining of the intestine, the skin and hair are exposed to a harsh external
environment—including ultraviolet radiation from sunlight—and are continuously renewed
throughout life. The skin consists of three major cell lineages:
the epidermis, hair follicles, and sebaceous glands, which release oils that
lubricate the skin surface

Satellite cells
are located beneath the basal lamina of muscle fibers (Figure 19.9).
They are normally quiescent, arrested in the G0 phase of the cell cycle,
but are activated to proliferate in response to injury or exercise. Once
activated, the satellite cells give rise to progeny that undergo several
divisions and then differentiate and fuse to form new muscle fibers.
The continuing capacity of skeletal muscle to regenerate throughout
life is due to self-renewal of the satellite stem cell population.
●Stem cells have also been found in many other adult tissues, including
the brain and heart, and it is possible that most—if not all—tissues contain
stem cells with the potential of replacing cells that are lost during the
lifetime of the organism. It appears that stem cells reside within distinct
microenvironments, called niches, which provide the environmental
signals that maintain stem cells throughout life and control the balance
between their self-renewal and differentiation
Figure 19.9 Muscle satellite cells The stem cells of skeletal muscle are the satellite cells,
located beneath the basal lamina of muscle fibers.

Medical applications of adult stem cells

The ability of adult stem cells to repair damaged tissue clearly suggests their
potential utility in clinical medicine. If these stem cells could be isolated and
propagated in culture, they could in principle be used to replace damaged
tissue and treat a variety of disorders, such as diabetes or degenerative diseases like
muscular dystrophy, Parkinson’s, or Alzheimer’s

A well-established clinical application of adult stem cells is hematopoietic


stem cell transplantation (or bone marrow transplantation), which plays an
important role in the treatment of a variety of cancers. As discussed in Chapter
20, most cancers are treated by chemotherapy with drugs that kill rapidlydividing cells by
damaging DNA or inhibiting DNA replication. These drugs
do not act selectively against cancer cells and so are also toxic to those normal
tissues that are dependent on continual renewal by stem cells, such as blood,
skin, hair, and the intestinal epithelium. The hematopoietic stem cells are among
the most rapidly dividing cells of the body, so the toxic effects of anticancer
drugs on these cells frequently limit the effectiveness of chemotherapy in cancer
treatment. Hematopoietic stem cell transplantation provides an approach to
bypassing this toxicity, thereby allowing the use of higher drug doses to treat
the patient’s cancer more effectively. In this procedure, the patient is treated
with high doses of chemotherapy that would normally not be tolerated because
of toxic effects on the hematopoietic system (Figure 19.11)
Embryonic stem cells

●While adult stem cells are difficult to isolate and culture, it is relatively straightforward to
isolate and propagate the stem cells of early embryos (embryonic
stem cells). These cells can be grown indefinitely as pure stem cell populations
while maintaining the ability to give rise to all of the differentiated cell types
of adult organisms (pluripotency)

Somatic cell nuclear transfer


The isolation of human embryonic stem cells in 1998 followed the first
demonstration that the nucleus of an adult mammalian cell could give rise
to a viable cloned animal. In 1997 Ian Wilmut and his colleagues initiated
a new era of regenerative medicine with the cloning of Dolly the sheep
(Figure 19.14). Dolly arose from the nucleus of a mammary epithelial cell
that was transplanted into an unfertilized egg in place of the normal egg
nucleus—a process called somatic cell nuclear transfer.

Animal cloning by somatic cell nuclear


transfer, together with the properties of embryonic stem cells, opens the possibility of
therapeutic cloning (Figure
19.15). In therapeutic cloning, a nucleus from an adult human cell would be
transferred to an enucleated egg, which would then be used to produce an
early embryo in culture. Embryonic stem cells could then be cultured from
the cloned embryo and used to generate appropriate types of differentiated
cells for transplantation therapy. Human embryonic stem cells were first
produced by somatic cell nuclear transfer in 2013, supporting the possibility
of this approach. The major advantage provided by therapeutic cloning is
that the embryonic stem cells derived by this procedure would be genetically identical to the
recipient of the transplant, who was the donor of the
adult somatic cell nucleus. This bypasses the barrier of the immune system
in rejecting the transplanted tissue.

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