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