How are stem cells used for longevity, regenerative medicine, disease therapy? How were stem cells discovered and first used? Learn more!

1. The DNA Universe

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The beginnings of stem cell therapy
Eurofins Genomics - The DNA Universe
The Axolotl and starfish are known for extraordinary ability to regrow limbs,
organs and even parts of the brain and heart.
The secret of this ability: unique cells that are capable of de-differentiating
(from muscle or skin cells) back into stem cells.
These stem cells are then able to proliferate and re-differentiate to give
rise to any other cell type.

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Stem cell therapy – A matter of the heart
Case study:
Dave Randle, 49 years old, had a heart attack in March 2016:
Suffered from heart failure with dyspnea
(breathing difficulties due to fluid build-up in the lungs).
Had dimnished abilities to exert any effort.
Stem cell therapy:
Stem cells were infused into his heart to
restore the function of the damaged tissues.
Results:
Improvement of condition within weeks of
treatment.
Mr. Randle went back to performing everyday
activities.

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Eurofins Genomics - The DNA Universe
Stem cell therapy – The beginning
1958
French oncologist, Georges Mathé, performed first
stem cell transplantation:
Bone marrow grafts for six nuclear researchers
who were exposed to radiation.
1960s
Ernest McCulloch and James Till discovered haematopoietic
stem cells (HSCs):
They demonstrated the role of HSCs in blood cell
formation in mice.
HSCs were shown to self-renew, one of the defining
features of stem cells.
1963
Georges Marthé cured a case of leukaemia using
bone marrow transplantation.

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Stem cell therapy – The beginning
Depiction of haematopoiesis.

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Embryonic stem cells
Embryonic stem cells (EST)
are pluripotent.
Can give rise to any
type of cell in the body.
Have not undergone any
stage of differentiation.
Formed in the blastocyst.
Depiction of embryonic stem cell differentiation.
Human embryonic stem cells.

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Eurofins Genomics - The DNA Universe
Adult stem cells
Adult stem cells are more specialised than embryonic stem cells.
Can be found in different organs throughout the body, where they divide
and further differentiate to replenish lost cells.
Are multipotent and can only differentiate into specific cell types;
e.g. neural stem cells can only differentiate into glial and neuronal cells.
Another type of adult stem cells:
Mesenchymal stem cells (mesenchymal stromal cells)
Can differentiate into a variety of cell types.
Can be induced to differentiate into neuronal precursors and mature
neurons – potential treatment of central nervous system disease.
Can modulate innate immune response and provide trophic support.

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Induced pluripotent stem cells
Induced pluripotent stem cells (iPSCs) are somatic cells:
Can be converted into stem cells through introduction of specific genes,
e.g. Myc, Oct3/4, Sox2 and Klf4 that encode Yamanaka factors
(transcription factors).
Are converted into pluripotent stem cells.
Yamanaka factors:
Discovered by Dr. Shin’ya Yamanaka in 2006.
Remove the identity of a cell (de-specialisation).
Revert the cell back to its embryonic state.
Exposing cells to lower doses of Yamanaka factors
for a shorter time resulted in age reversal without
subsequent loss of cell identity.
Yamanaka factors were
discovered by Dr. Shinya
Yamanaka in 2006

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Induced pluripotent stem cells
Depiction of generating induced
pluripotent stem cells.

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Induced pluripotent stem cells
iPSCs carry the patient’s DNA.
Therefore, low risk of immune system reaction or rejection.
Avoiding controversy of using embryos for therapeutic purposes.
Advantages of iPSCs:
Stem cells derived from iPSCs of a patient with Huntington's Disease (immunostaining
for different stem cell markers).

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The fate of stem cells
Stem cells do not differentiate or divide e.g. haemopoietic cells waiting for
stimuli.
Stem cells divide to give rise to exactly identical daughter cells - daughter
cells contribute to stem cell pool.
Stem cells divide into two cells - one is identical to the parent stem cell,
other is a more differentiated cell called a progenitor.
Stem cells divide to give rise to two more differentiated daughter cells with
loss in the stem cell pool.
Quiescence:
Symmetric self-renewal:
Asymmetric self-renewal:
Symmetric division without self-renewal

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Eurofins Genomics - The DNA Universe
Induced pluripotent stem cells
Depiction of the fate
of stem cells.

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The binnings of stem cell therapy
The journey of stem cell therapy started with a bone marrow transplant
over 60 years ago.
It has flourished throughout the years and is used as therapeutic approach
for many incurable diseases, e.g. multiple sclerosis.
Longevity-associated genes
Mechanisms of tumourigenesis
Regenerative medicine
Stem cells are used for research on:
Summary:

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