Altruistic Stem Cell Behavior May Indicate Cancer Link: Study by Bikul Das and Team

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Dr. Bikul Das

A new study conducted by Dr. Bikul Das and his team at the Stanford University School of Medicine has shown that embryonic stem cells exhibit altruistic behavior which may have a link to cancer, reports the Science Daily. In the new study, human embryonic stem cells (hESC), in times of stress have been found to produce molecules that help neighboring cells survive. This is the first time that altruistic behavior is being reported and described at the cellular level in mammals, says Dr. Bikul Das, MBBS, PhD.

Altruism is a known concept in bacterial populations and this behavior helps them to survive and grow together as a colony. However, altruism has not been previously observed or studied at the cellular level in mammalian cells. Even though, altruism is considered a ‘virtue’, in this paper Dr. Das studies altruistic hESCs which tend to accumulate mutations and hence may give rise to cancers. Let us see how this unique study proceeded…

Background and beginning…

Dr. Das was researching about how the hESC react in low oxygen levels…akin to the environment in a cancerous tumor. hESC have the ability to differentiate into various cell types and Dr. Das found that in low oxygen environments with only 1/10^th % of oxygen, hESC produced free radicals that caused internal cell damage. 90% of the hESCs differentiated into other cell types or died while 10% of the hESCs retained their ability to differentiate…in other words…they retained their stemness. Thus, Dr. Das went on to explore why 10% of the cells were able to retain their stemness and what set them apart.

Studying hESC…

Dr. Das and his team decided to identify and segregate these hESC based on the molecules they produced. They found that:

Half of the 10% of hESCs that survived low oxygen environment and retained their stemness contained high levels of HIF2-alpha – a protein that turns up the production of antioxidant molecules, and low levels of p53 – a protein that induces cell death in the event of too much DNA damage.
These levels could keep the stem cells alive and undifferentiated.
The other half of hESC showed normal levels of HIF2-alpha and p53. There was no explanation as to how these cells remained alive without differentiation, unless they were being helped by other cells.
Dr. Das and his team began to suspect altruism among hESCs.

Testing theory of Altruism in hESC

Das and team at University of Toronto began work…

They soaked hESC with high levels of HIF2-alpha and low levels of p53 in a culture medium for 24 hours.
They removed the cells from the medium.
Now, they added the hESC with medium levels of HIF2-alpha and p53.
They found that the cells remained alive and retained their stemness.
Hence, there was something in the medium that kept them from differentiating.
This molecule was found to be antioxidant, GULTATHIONE.

Dr. Das and his team went on to find that the level of p53 fluctuates in a set pattern in the stem cells during stress.

Discovery and Significance

Human embryonic cells under stress exhibit high levels of HIF2-alpha and p53 normally, hence most of them either die or differentiate. The study is unique since it shows the existence of altruistic cells among the hESC which exhibit low levels of p53 and this keeps the cells from differentiating or dying. The discovery has two significances:

The stem cells with low p53 have a disadvantage in that they tend to accumulate mutations. Cells with mutations can become cancerous.
The understanding of p53 fluctuations in stem cells can benefit scientists who use engineered stem cells for treating diseases. These stem cells need to be able to retain their stemness to be effective.

Dr. Das and his team are continuing to study the concept of altruism in mesenchymal and blood stem cells.

The study has since been published in the journal, Stem Cells.