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BASIC BIOLOGY OF STEM
CELLS
STEM CELL – DEFINITION
Stem cells are undifferentiated mass of cells that has the
ability to continuously divide and differentiate (develop)
into various other kind(s) of cells/tissues.
The human body has a variety of 220 different cells types.
Stem cells are master cells that act as foundation cells for
every organ, tissue and cell in the body..
They are considered as a blank microchip that can be
programmed to perform particular tasks. They serve as a
repair machine for the body.
STEM CELL CHARACTERISTICS
‘Blank cells’ (unspecialized)
Capable of dividing and renewing themselves for
long periods of time (proliferation and renewal)
Have the potential to give rise to specialized cell
types (differentiation)
CLASSIFICATION OF STEM CELLS BASED ON POTENCY
Stem cells can be classified into four broad categories, based on their ability to
differentiate
Totipotent stem cells are found only in early embryos. Each cell can form a
complete organism (1-3 days) .
Pluripotent stem cells exist in the undifferentiated inner cell mass of the
blastocyst (5 to 14 days) and can form any of the over 200 different cell types
found in the body. stem cells can form most or all cell types in the adult
Multipotent stem cells are derived from fetal tissue, cord blood, and adult stem
cells. These cells are differentiated, but can form a number of other tissues. stem
cells can form multiple types of cells and tissue types
Unipotent are able to contribute to only one mature cell type but have the
property of self-renewal which distinguishes them from non-stem cells
A life story…
TOTIPOTENCY
Pluripotent stem cells – more potential to become any type of cell
Multipotent stem cells –
limited in what the cells can
become
The classical definition of a stem cell requires that it possess
two properties:
Self-renewal: the ability to go through numerous cycles of cell
division while maintaining the undifferentiated state.
Potency: the capacity to differentiate into specialized cell
types. In the strictest sense, this requires stem cells to be
either totipotent or pluripotent—to be able to give rise to any
mature cell type, although multipotent or unipotent progenitor
cells are sometimes referred to as stem cells. Apart from this it
is said that stem cell function is regulated in a feed back
mechanism.
SELF-RENEWAL
Two mechanisms exist to ensure that a stem cell population is
maintained:
Obligatory asymmetric replication: a stem cell divides into one
mother cell that is identical to the original stem cell, and
another daughter cell that is differentiated
Stochastic differentiation: when one stem cell develops into two
differentiated daughter cells, another stem cell undergoes
mitosis and produces two stem cells identical to the original.
Potency definitions
Stem cell differentiation and proliferation
1: symmetric stem cell division;
2: asymmetric stem cell division;
3: progenitor division;
4: terminal differentiation
A: stem cell;
B: progenitor cell;
C: differentiated cell;
Difference between stem cell and progenitor cell
Embryonic stem cells
•five to six-day-old embryo
•Tabula rasa
Embryonic germ cells
•derived from the part of a human embryo or fetus that will ultimately
produce eggs or sperm (gametes).
Adult stem cells
•undifferentiated cells found among specialized or differentiated cells in a
tissue or organ after birth
•appear to have a more restricted ability to produce different cell types and
to self-renew.
Further classification
Embryonic stem cells
• Cells found early (less than 2 wks.) in the development of an embryo
• Embryonic stem cells are the most versatile because they can become
any cell in the body including fetal stem cells and adult stem cells.
• Embryonic stem (ES) cells are taken from inside the blastocyst, a very
early stage embryo. The blastocyst is a ball of about 50-100 cells and
it is not yet implanted in the womb. It is made up of an outer layer of
cells, a fluid-filled space and a group of cells called the inner cell
mass. ES cells are found in the inner cell mass.
ISOLATION OF HUMAN EMBRYONIC STEM CELLS
In vitro fertilization technique
Cleavage 8 cell stage
Blastocyst Blastocyst inner cell mass
Stages of embryogenesis
Embryonic germ cells
Human embryonic germ cell (EG cells) normally develop into eggs
and sperm. They are derived from a specific part of the embryo
called the gonad ridge, and are isolated from fetuses older than 8
weeks of development.
One advantage of embryonic germ cells cells is that they do not
appear to generate tumors when transferred into the body, as
embryonic stem cells do.
One of the greatest issues facing researchers is that the derivation
of EG cells results from the destruction of a foetus. EG cells are
isolated from terminated pregnancies and no embryos or foetuses
are created for research purposes.
ADULT STEM CELLS Adult stem cells are found in the human body and in
umbilical cord blood.
The most well known source of adult stem cells in the body is
bone marrow but they are also found in many organs and
tissues; even in the blood.
Adult stem cells are more specialized since they are assigned
to a specific cell family such as blood cells, nerve cells, etc.
Recently, it was discovered that an adult stem cell from one
tissue may act as a stem cell for another tissue, i.e. blood to
neural
Adult Stem Cells An undifferentiated cells found
among specialized or
differentiated cells in a tissue
or organ after birth
Also Known as Wharton‟s Jelly
Adult stem cells of infant origin
Less invasive than bone marrow
Greater compatibility
Less expensive
Umbilical cord stem cells
Umbilical cord stem cells
Three important functions:
1.Plasticity: Potential to change into other
cell types like nerve cells
2.Homing: To travel to the site of tissue
damage
3.Engraftment: To unite with other tissues
HEMATOPOIETIC STEM CELLS
Hematopoietic stem cells are those cells from where all blood cells originate.
Discovery of hematopoietic stem cells in cord blood was made in the year 1974.
In the year 1982 Broxmeyer suggested umbilical cord blood contained significant amount of hematopoietic stem cells suitable for transplantation
Pluripotent :- red cells, white cells and platelets
High proliferative capacity : 1 cell in a million
Sources of hematopoietic stem cells in human
1. Umbilical Cord blood.
2. Peripheral blood.
3. Bone marrow
Mesenchymal Stem Cells
Mesenchymal stem cells (MSCs), also called bone marrow
stromal cells, are multipotent stem cells that differentiate into
a variety of cell types, including:
−osteoblasts(bone cells)
−chondrocytes(cartilage cells)
−adipocytes(fat cells).
Human MSCs are of interest in clinical applications due to:
−Capacity for homing and engraftment
−Wide-range differentiation potential
−Immunosuppressive attributes
Potential MSC Therapies:
−Graft versus Host Disease
−Crohn’s Disease
−Bone Defects/ Genetic Disease
−HSC Transplantation
−Cardiac repair
−Trachea repair
Induced pluripotent stem cells (iPSCs)
adult cells that have been genetically reprogrammed to an embryonic stem cell–like state by being forced to express genes and factors important for maintaining the defining properties of embryonic stem cells
Why the Controversy Over Stem cells?
•Embryonic Stem cells are derived from extra blastocysts
that would otherwise be discarded following IVF.
•Extracting stem cells destroys the developing blastocyst
(embryo).
-Questions for Consideration-
•Is an embryo a person?
•Is it morally acceptable to use embryos for research?
•When do we become “human beings?”
Reference
“STEM CELLS” by C.S.Potten