Stem Cells

Zahraa A. Watad
zahraawatad@gmail.com
Dubai, UAE
Outline

Introduction

Classification Of Stem Cells

Types of Stem Cells and Sources

History of Stem Cells

Techniques to produce Stem Cells

Challenges

Applications of Stem Cells

Future Prespectives
 Introduction

Stem Cells are defined as precursor cells that have the

capacity to self-renew and to generate multiple mature cell
types.

Self-renewal refers to the ability of a stem cell to divide and

make identical copies of itself to assure that the stem cell
population is not depleted.

Stem cells may be slow to divide and are mostly thought to be

quiescent in the body, preserving their potential until needed.

Differentiation is the process whereby stem cells transform

into more specialized cell types and can perform new
functions
through the expression of new genes, mRNA, and proteins.
Classification of Stem Cells
 Classification of Stem Cells

The number of cell types a stem cell can differentiate into is determined by its potency:

Totipotent stem cells have the ability to form

an entire organism. The fertilized oocyte and the
cells after the first cleavage divisions are considered
to be totipotent.

Pluripotent stem cells are able to form all three germ

layers including germ cells,
Cells of the Inner Cell Mass (ICM) of the blastocyst are
pluripotent.
When these cells are brought into culture,
they are called Embryonic Stem Cells.
 Classification of Stem Cells

The number of cell types a stem cell can differentiate into is determined by its potency:

Multipotency means the ability to form multiple cell types.

MSCs can differentiate into cells that form bone, cartilage, and fat.

Oligopotent stem cells can differentiate into two or more lineages,

for example, neural stem cells that can form a
subset of neurons in the brain.

Unipotency is the ability to form cells of a single lineage,

for example, spermatogonial stem cells.
Typpes of Stem Cells
 Types of Stem Cells | Embryonic Stem Cells

1- EMBRYONIC STEM CELLS

Source: Blastocyst

Embryo is the organism from the time of implantation in the uterus until the end of the second month of
gestation. Embryonic stem cells (ESCs), however, refer to a much more restricted period, resulting from
the isolation and cultivation of cells from the blastocyst, which forms at approximately 5 days after
fertilization.
 Types of Stem Cells | Embryonic Stem Cells

EMBRYONIC STEM CELLS CHARACTERISTICS:

- Pluripotent
- Immortal in culture
- They maintain a normal chromosomal composition.
- They are known to express surface markers such as CD9, CD24,
and alkaline phosphatase, and several genes involved with pluripotency,
including Oct-4, Rex-1, SOX-2, Nanog, LIN28, Thy-1, and SSEA-3 and -4.
- Expression of high levels of telomerase
 Types of Stem Cells | Embryonic Stem Cells

Embryonic Stem Cells in RESEARCH:

In 1998, the first human ESC line was generated.

ESC research focuses mainly on two issues,

1- How to better maintain the cells in long-term culture, without significant modifications of their genetic
composition.

2-How to differentiate the cells into the many mature cell types

A technical challenge is to control the differentiation process

 Types of Stem Cells | Induced Pluripotent
Cells
2- Induced Pluripotent Stem Cells ( IPSC)

Source: Adult Mature Cells.

- Direct reprogramming of adult cells to induced pluripotent stem cells.

- iPS cells are produced by treating mature cells, such as fibroblasts,

with genes that ‘dedifferentiate’ them to a pluripotent stage, similar to an
embryonic stem cell.

-Viral vectors, such as retroviruses, are generally used for gene transfer

-Expression of specific genes and proteins, chromatin methylation patterns,

culture kinetic, in vitro differentiation patterns, and teratoma formation
 Types of Stem Cells | Adult Stem Cells

3- ADULT STEM CELLS

Source: Somatic Stem Cells.

Include : Hematopoietic, Epithelial, Muscular, and Neural stem

cells

- Rare, quiescent cells with a more limited self-renewal

and differentiation capacity.

- All tissues have their own compartment of stem cells.

- They are responsible for replenishing cells that die within a

given organ, either due to physiological (wear and tear) or
pathological processes.
 Types of Stem Cells | Mesenchymal Stem
Cells
4- MESENCHYMAL STEM CELLS ( MSCS)

Source: Bone Marrow & Adipose Tissue

-Are multipotent stromal cells that can differentiate into a

variety of lineages.

- MSCs are attractive for clinical therapy because of the

following characteristic;

• Easy in vitro expansion

• Ability to differentiate into a variety of tissues
• Provision of trophic support
• Modulation of immune responses
Stem Cells in Research
 Stem Cells in Research.

From Discovery to clinical trials

Techniques
 Techniques to Produce Stem Cells

1- Cell Reprogramming.

Treating Human Adult Fibroblasts with 4 genes; Oct3/4, Sox2, Klf4, and c-Myc to reprogram to
Induced Pluripotent Stem Cells.

PSCs cells have been generated also from other cell types including adult hepatocytes, gastric
epithelial cells, and mesenchymal cells
 Techniques to Produce Stem Cells | iPSCs

These discoveries have generated an unprecedented deal of interest toward stem cell research, mostly for these
reasons:

iPSCs generation does not require the use (and disruption) of

embryos

In-vitro Expansion

iPSCs can be patient customized.

 Techniques to Produce Stem Cells | iPSCs

Challenges to be addressed:

The possible incomplete reprogramming

The safety of the reprogramming process,

The epigenetic differences between ES and IPS cells

The need of efficient methods to induce the differentiation

of IPS (or ES) cells into the desired cell type
 Techniques to Produce Stem Cells

2- Therapeutic Cloning (somatic cell nuclear transfer)

 is a technique to create versatile stem cells independent

of fertilized eggs. 

In this technique, the nucleus is removed from an unfertilized egg.

This nucleus contains the genetic material.
The nucleus is also removed from the cell of a donor.

This donor nucleus is then injected into the egg, replacing the nucleus
that was removed, in a process called Nuclear Transfer. The egg is
allowed to divide and soon forms a blastocyst.
This process creates a line of stem cells that is genetically
identical to the donor's cells — in essence, a clone.
 Techniques to Produce Stem Cells

3- IVF ( In-Vitro Fertilization)

This technique is used to produce Embryonic Stem Cells.

Allow the fertilized egg to grow in the lab, until the embryo is formed, a screening is done to use the healthy
embryo in treatment of infertility and the rest of the eggs are used to produce Embryonic Stem Cells.

- Ethical Concerns
Challenges
 Challenges

• Further optimization of their expansion and differentiation into function cell types is required.

• Current methods for deriving these cell lines and maintaining them in culture is time-consuming, labor-
intensive, and their chemically defined media is expensive.

• Avoiding the use of animal product as feeder cells

• Immune rejection

• Purification of differentiated cell types

• Political and Ethical Concerns

Applications
 Applications

• Human ES and iPS cells can be used as a model system to study human embryonic development
and differentiation

• Study the development and characteristics of these diseases in vitro.

• Pluripotent stem cell lines could be a useful resource for preclinical stem cell research and developing ES
and IPS cell-based transplantation therapies.

• Stem cells as a target for pharmacological testing

• Regenerative Medicine
Future Perspectives
 Future perspectives

• Translational Research

The importance of translational research lies in it’s a role as a filter to ensure that only safe and effective
therapies reach the clinic

• Clinical Trials

There are more than 3,000 trials involving the use of adult stem cells registered in WHO international
clinical trials registry
 References.

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4485209/

• https://www.nature.com/articles/cdd201014

• https://www.mayoclinic.org/tests-procedures/bone-marrow-transplant/in-depth/stem-cells/art-20048117

• https://www.sciencelearn.org.nz/resources/1965-stem-cells

• https://learn.genetics.utah.edu/content/stemcells/quickref

• Biology of stem cells: an overview

• Current state of stem cell-based therapies: an overview

• Stem cells: past, present, and future