Stem Cells

Advertisements of umbilical cord banking have been surfacing for many years now. To quieten my curious mind with the many doubts I had about this therapy and its importance, I spoke to PhD students working in the Vascular Biology lab of Principle Investigator Prof. Maneesha Inamdar in Jawaharlal Nehru Centre for Advanced Scientific Research. Here are excerpts from my discussion with them on their research.

In layman's terms, what are stem cells and why are they important?

Deeti Shetty: 

Stem cells are of different types based on their potency. Pluripotent cells are cells which are most primitive; they give rise to an organism. Interest was born in Embryonic Stem Cells (ESC) because from these cells you can give rise to all cell types in your body. They self-renew & they can also differentiate into various types. We study the transition of embryonic stem cells to adult cells & also how these cells are formed.

And what are the medical applications of stem cells?

Adult stem cells are used for bone marrow replacement therapy in cancer. In leukemia and blood cancer, they irradiate your bone completely, to kill the cancerous cells. Using molecular biology and genetic engineering, you can make corrections in genetic code (gene sequence defect) in the desired cells. The corrected gene can then be put into the body & in case of mice, it has led to cure. Efficiency can be improved by providing growth factors like cytokines so you get more of the desired cell type in culture. Applications have come into place but there are a lot of risks, like at places which do not have the capacity to purify the cells. Now after the differentiation, you do not want additional stem cells as that itself can cause a tumor. So you should be very careful with the facilities you visit to carry out these processes & check whether they have an established protocol. It is an expensive process especially in cases of donor dependency. Criteria of a donor include willingness to donate, match of blood group and antigen recognition. 

Can it be artificially generated?

Yes, it can. You can modulate a given cell type. Research is on to make adult cells, like differentiated skin cells, stem cell like. This process is called re-programming or de-differentiation. Pluripotent cells are generated in this process. Suppose an adult's parent had not preserved the umbilical cord or say you have no clue as to what this person’s history is. Nothing else is available so it has to be derived from your body. Conversion of a specific cell to induced pluripotent cells and further to desired cells takes days. In this duration, a person in emergency might collapse. So we're trying to find ways of shortening this duration. There is nano-technology where in beads are employed to carry proteins or growth factors to guide it to the correct place using antibodies. These beads open to deliver factors which promote cell growth.

How do you choose your model systems?

Simi Muraleedharan: 

I am trying to understand the function of a protein in kidney cells & then relate it to the cardiovascular diseases or the development of cardiovascular system. The protein I am working on is required for the cardiovascular development. Blood vessels develop with the help of this protein. Since we can’t work on humans, we have model systems which have the advantage of short life span and ease of genetic manipulation. I am working on mouse & then will be able to relate it to human kidney. Fruit flies have small kidney like organs, so even in them we can find these proteins. We are doing basic research. If we have to target this molecule for treatment purpose, we need to first understand how this protein functions. That is the phase I am in.

What is the significance of this research to society?

Praveen W:

I am currently working on stem cell biology, my area being re-programming. Stem cells are the cells which have the capacity to differentiate into different kinds of cells. The work I do is haemopoetic development which is differentiation of the stem cell into blood lineage cell. We want to see which genes can affect haematopoiesis, which is the formation of blood cells in the body. My tool to study this aspect is mouse embryonic stem cell. The significance of this research to general public is that we report genes having a role in leukemia or other blood related malignancies, so we can devise small molecule through which these malignancies can be controlled or regulated. Our lab also works on identifying novel ways to be able to generate induced pluripotent stem cell’s efficiency. We are at a phase of basic research. It'll take a long time to bring this out to general public.

Are there any shortcomings or side effects?

Disadvantages come when applications are carried out without proper knowledge. There are cases where renowned hospitals use these under developed techniques & patients end up with another set of problems. In labs, we can experiment, where in the outcome is expected & sometimes out of our expectations. But before moving to complex organisms like human beings, there are many factors to consider that cannot be replicated in the lab. So for clinical usage, expected outcomes should be validated in animal models before application. These precede pre-clinical trials on humans. There is always a probability for randomness though, as each patient is different genetically. 

There are cases when patients have suffered wrong treatment and were administered with adult stem cells of one organ for treatment of another anticipating trans-differentiation which failed. One should understand limits of using stem cells from one tissue to another. Therapeutic complications of using one healthy donor’s stem cells in another patient involve rejection of cells by immune system (which is the same as in case of organ transplant operations). The HLA antigen is different for each individual & immune rejection depends on that. In umbilical cord stem cells, immune rejection is avoided as I am not using someone else’s cells. Thus banking these cells with credible stem cell banks (Government approved and affiliated with hospital and research institutions) is a good way to have a stem cell resource at the time of need during accidental emergencies.