College aantekeningen
Aantekeningen colleges 1-12 | 8WC00 Regeneration
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Aantekeningen colleges 1-12
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Aantekeningen college 1Introduction
Regenerative medicine is the biological capacity of tissue to regenerate itself.
This study is focussed on cells, tissues and organs and how they grow,
differentiate, remodel and repair.
There are three types of transplantation:
- Autotransplantation → tissue coming from patient’s body
- Xenotransplantation → non-living tissue coming from
laboratory
- Paratransplantation → tissue coming from different animal
Some animals have much stronger regenerating capabilities than others.
These animals are very interesting for research, in order to try and
understand what is happening inside their bodies.
Processes and mechanisms of growth
Definition growth
Growth is simply said, the increase in size of a tissue. The two main components that contribute to
tissue growth are cells and the ECM.
Cells contribute to growth in two ways:
- Cell size increase
- Cell number increase
The ECM contributes to growth by reorganisation and increase of density.
Processes of growth
Cells:
- Cell proliferation → rapid increase in numbers
- Cell death → caused by apoptosis
- Senescence/growth arrest → the condition of
deterioration with age, where cells are dysfunctional
but not dead yet
The Extracellular matrix:
- is a mesh of filamentous (glyco) proteins and
polysaccharides
- separates and encloses tissues and organs
- provides roads for cell migration
- regulates cell signaling
- is unique for different places
Connective tissues
,All connective tissues have a different tissue architecture. During ECM growth, this architecture must
be maintained. But in some diseases, this architecture changes like progeria where the shape of the
nucleus is distorted.
There are three main types of connective tissue:
- Loose connective tissue acts as padding under the skin (and elsewhere).
- Bone and cartilage are connective tissues made up of cells in a hard or stiff ECM.
- Blood is a connective tissue made up of cells in a liquid matrix.
Growth phases
In life, there are four phases of growth:
- Embryonic growth → massive
proliferation and differentiation
of cells until birth.
- Postnatal growth → further
development and
differentiation of cells until
adulthood. Pituitary gland only
increases size 5-10x, whereas
muscles increase size 30-40x.
- Homeostasis → maintenance of
all tissues until fifties.
homeostasis (and injury recovery) is made possible by tissue turnover, the
combination of apoptosis and proliferation.
- Aging → loss of tissue (function) until death due to lowering of turnover rate and
thus loss of regenerative capacity. also, the production and organisations of the
ECM are changed. E.g. less collagen fibers are produced within the skin, therefore
it becomes wrinkly.
Stem cells
Stem cells are the true building blocks for cell growth
and postnatal growth and homeostasis. The four
places where somatic stem cells occur are:
- Blood vessels
- Adipose tissue
- Bone marrow
These stem cells are very important for regenerative
medicine, for they’re easy to isolate, propagate and
have a high regenerative potential.
Usually, whenever cells have differentiated, they’re
not able to proliferate anymore. The only exception
to this rule are the differentiated cells within the liver
which are able to proliferate.
The number of stem cells within the body must be
controlled heavily, for a shortage of them will lead to
a loss of regenerative potential, but an increase (due to e.g. mutations)
will most likely lead to cancer.
Stem cells are surrounded by niches of other cells that help the stem
cells work properly. These niches contain:
- a specific location
, - supporting cells that protect from e.g. inflammation
- a specific chemical environment
- a specific mechanical environment
Maintaining stem cell integrity
In order to make sure, very few mutations take place within stem cells, the following mechanisms
arise.
- Asymmetric cell division
Since the stem cell population must be maintained small. Asymmetric cell division is used to ensure
that only one of the daughter cells stays a stem cell and the other cell becomes a committed transit
amplifying daughter cell. The environment determines the fate of the daughter cells.
- Immortal strand
Due to the asymmetric cell division, the old DNA strands are used after the division. This means that
the DNA of only one of the daughter cells has the original DNA strand.
- Prevention of aneuploidy
Aneuploidy will often result in developmental disorders, of which many are fatal. The main mechanism
that prevents this are dysfunctional mitotic checkpoints. These make sure that during cytokinesis, all
chromosome pairs are properly attached to the kinetochores.
In short, the stem cell integrity is maintained through:
- small population
- asymmetric cell division
- immortal strand
- control of cytokinesis
Difference between embryonic stem cells, adult stem cells and induced pluripotent stem cells
The main difference between embryonic and adult stem cells is that embryonic stem cells are
pluripotent and adult stem cells are multipotent. An iPC is synthetically created from a somatic cell.
Cell death
Difference between apoptosis and necrosis:
Apoptosis
Regulated cell death
No inflammation
Degradation and reuse of material
Phagocytosis of dead cell
Necrosis
Burst of cell
Release of cell components
Inflammation
Morphogenesis
, Apoptosis is a very important part of morphogenesis. For example when forming the digits, the
interstitial material must be removed by important apoptotic proteins such as Casp9.
Tissue renewal and regeneration
In most cases, differentiated cells aren’t able to proliferate any longer. Therefore, in order to contribute
to growth, these cells help to synthesise the ECM they’re embedded in. Cells have a limited capacity
to grow, since it’s energetically unfavorable to have the cell grow too large.
The turnover rate of the different organs is very different. Here
are some turnover rates of tissues:
- The GI tract renew within a week
- Blood cells renew within 90 days
- Liver renews within 2-3 years
- Lungs and pancreas renew within 4 years
- Heart renews within 15-20 years
- Brain renews within 20-30 years
Control of growth at the tissue level
Growth happens only on demand to for example injuries. This
demand is given by different stimuli:
- Contact inhibition
- Hormonal stimuli
- Neuronal stimuli
- Availability of nutrients
There are different parameters that will regulate the
ability to of cell proliferation:
- Ex- and intrinsic factors
- Availability of nutrients
- Signals from other cells
- Cell cycle control mechanisms
- Cell aging
- Nutrients, stress, mechanics, architecture
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