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Pressure & Practice

The bone marrow transplant has been used as a cancer therapy for over 50 years. It is designed to replace a patient’s defective stem cell population with a healthy donor pool. Three steps must occur. First, you need to condition the host and eliminate all of his/her current stem cells. This is done with either high dose chemotherapy or total body irradiation. Next, you must ‘rescue’ the host by giving them healthy stem cells. These can be autologous (harvested from the host prior to conditioning, if they are healthy) or allogeneic (from a matched donor). Finally, you need to ensure that the stem cells engraft – that they home to the host’s bone marrow and begin producing healthy blood cells.

Hematology researchers have adapted the transplant for animal studies. Highly sophisticated mouse models exist that allow researchers to study the development and biology of stem cells. Models that allow you to distinguish and track host cells vs. donor cells. Models that express specific mutations that mimic human diseases. Models that have allowed researchers to probe the very origin of stem cells and seek ways of generating them in a culture dish. Many cancer therapies have been developed and countless lives saved from this pioneering work.

However, the actual transplant procedure is technically challenging. The first step – conditioning with total body irradiation – will destroy the mouse’s immune system. If healthy stem cells are not provided within a narrow time window, these irradiated mice will develop infections, anaemia, and will die. The challenge is that the healthy stem cells must be given to the mouse by an intravenous route. This is done by a tail vein injection: using a 30 gauge needle – the smallest we have in our lab –you try to hit the tiny, minuscule, impossibly, freakishly small vein that runs the length of the mouse’ tail.

Did I mention that if you miss the vein, the mouse will not get stem cells, will develop infections, and will die?

Did I mention that with each attempt to prick the vein, you increase the likelihood that the vein will spasm and close off?

Did I mention that each prick increases the possibility of infection?

Did I mention that I am performing my first transplantation experiment tomorrow?

Talk about a high pressure situation.

This is not a procedure to be done haphazardly. You need a great mentor (thanks Momoko!) to teach you the tricks: keep the tail as parallel to the needle as possible, use a durable but minimal mouse restraint, heat up the mouse to engorge its vein. Success takes some skill but more so it takes patience and practice and more practice. So over the past week, I have been practicing my tail vein injections on non-irradiated wild type mice. I’ve tracked my progress. How do you think I’ve done? Should I be worried for tomorrow? Should the mice be worried?

 

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The views expressed in this content represent the perspective and opinions of the author and may or may not represent the position of Indiana University School of Medicine.
Author

Stefan Tarnawsky

MS4 MD/PhD Student. Going into Internal Medicine; interested in Heme/Onc. Bread baker, bonsai artist, aspiring astronomer.