Oncology 8
HC 4
8.1
We as humans arise from a clump of cells, or rather embryonic stem cells, located in the
inner cell mass arisen from a fertilized egg. These gradually become more specialized and
differentiate towards a particular function and cell type, whereby in the end each contribute
to the functioning of the entire organism. The regulation of a particular subset of genes,
defines the (future) cell type – every cell has the same genome, but every cell is different in
morphology and function due to differential expression.
Stem cells have the ability to self-replicate for indefinite periods throughout the life of an
organism, self-renewal. Moreover, they can do so and differentiate into many different cell
types, depending thus on the signals – they are pluripotent. Signals as in lineage-specific
transcription factors and epigenetic mechanisms (DNA methylation, histone modification,
etc.). The epigenetic changes are reversible, and the reversal thereof potentially can
reprogram a differentiated cell to become a stem cell again. Whenever a stem cell divides
and differentiates, it does as asymmetrically, so that from one stem cell, a new daughter
stem cell and a terminally differentiated cell arises; so, the stem cell population does not
decrease.
Stem cells are subdivided based on the extent of their ability to become differentiated cells.
There are totipotent stem cells, which can create any type of cell necessary for embryonic
development (including extraembryonic membranes). Pluripotent cells can develop into any
cell originating from one of the germ layers. Multipotent cells give rise to cells that have a
function originating from one specific germ layer. Furthermore, there is a distinction
between embryonic and adult stem cells. Embryonic ones are derived from the inner cell
mass and are pluripotent. Adult cells are involved in the continuous regeneration of tissues
during the lifetime, to replace dying cells – hence they are believed to reside in every tissue.
So, there are hematopoietic stem cells, intestinal stem cells, etc. The use of stem cells has
been proven to be useful to treat diseases, as this means there is no need of another donor,
and thus no autoimmunity; treating skin injuries and bone marrow transplantations use
stem cells.
Especially the pluripotent stem cells are interesting to use as therapy. They are harvested
from fertilized embryos, but due to ethical concerns, new techniques have been developed.
One is nuclear transfer, whereby an enucleated egg cell is ‘mixed’ with the nucleus of
another egg cell, and then transplanted into a surrogate. This technique gave rise to the
cloned sheep, Dolly. Research showed that cytoplasmic factors of a recipient enucleated cell
are able to reprogram the differentiation status as defined by the donor nucleus of another
cell. Another way of harvesting stem cells is through induction of pluripotent stem cells from
mouse embryonic and adult fibroblast cultures. If fibroblasts are exposed to specific factors,
introduced by retroviruses, it can transform into a pluripotent stem cell – it is
reprogrammed.
In the end, there ought to be a balance between stem cell renewal and differentiation,
whereby a disbalance in favor of self-renewal is a hallmark of cancer. Tumor cells actually
mimic stem cells to this extent, and cancer stem cells thus acquire self-renewal.
Stem cells are characterized by their ability to self-renew and their ability to give rise to
committed progenitors of differentiated cells – two features they share with cancer stem
HC 4
8.1
We as humans arise from a clump of cells, or rather embryonic stem cells, located in the
inner cell mass arisen from a fertilized egg. These gradually become more specialized and
differentiate towards a particular function and cell type, whereby in the end each contribute
to the functioning of the entire organism. The regulation of a particular subset of genes,
defines the (future) cell type – every cell has the same genome, but every cell is different in
morphology and function due to differential expression.
Stem cells have the ability to self-replicate for indefinite periods throughout the life of an
organism, self-renewal. Moreover, they can do so and differentiate into many different cell
types, depending thus on the signals – they are pluripotent. Signals as in lineage-specific
transcription factors and epigenetic mechanisms (DNA methylation, histone modification,
etc.). The epigenetic changes are reversible, and the reversal thereof potentially can
reprogram a differentiated cell to become a stem cell again. Whenever a stem cell divides
and differentiates, it does as asymmetrically, so that from one stem cell, a new daughter
stem cell and a terminally differentiated cell arises; so, the stem cell population does not
decrease.
Stem cells are subdivided based on the extent of their ability to become differentiated cells.
There are totipotent stem cells, which can create any type of cell necessary for embryonic
development (including extraembryonic membranes). Pluripotent cells can develop into any
cell originating from one of the germ layers. Multipotent cells give rise to cells that have a
function originating from one specific germ layer. Furthermore, there is a distinction
between embryonic and adult stem cells. Embryonic ones are derived from the inner cell
mass and are pluripotent. Adult cells are involved in the continuous regeneration of tissues
during the lifetime, to replace dying cells – hence they are believed to reside in every tissue.
So, there are hematopoietic stem cells, intestinal stem cells, etc. The use of stem cells has
been proven to be useful to treat diseases, as this means there is no need of another donor,
and thus no autoimmunity; treating skin injuries and bone marrow transplantations use
stem cells.
Especially the pluripotent stem cells are interesting to use as therapy. They are harvested
from fertilized embryos, but due to ethical concerns, new techniques have been developed.
One is nuclear transfer, whereby an enucleated egg cell is ‘mixed’ with the nucleus of
another egg cell, and then transplanted into a surrogate. This technique gave rise to the
cloned sheep, Dolly. Research showed that cytoplasmic factors of a recipient enucleated cell
are able to reprogram the differentiation status as defined by the donor nucleus of another
cell. Another way of harvesting stem cells is through induction of pluripotent stem cells from
mouse embryonic and adult fibroblast cultures. If fibroblasts are exposed to specific factors,
introduced by retroviruses, it can transform into a pluripotent stem cell – it is
reprogrammed.
In the end, there ought to be a balance between stem cell renewal and differentiation,
whereby a disbalance in favor of self-renewal is a hallmark of cancer. Tumor cells actually
mimic stem cells to this extent, and cancer stem cells thus acquire self-renewal.
Stem cells are characterized by their ability to self-renew and their ability to give rise to
committed progenitors of differentiated cells – two features they share with cancer stem
