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Homing Stem Cell Missile Treatments

Another month, another paper

This month’s paper is about stem cells: those unique cells within the body which have the capacity to assume different roles. While people have talked at lengths about the potential for stem cells to function as therapies, one thing holding them back (with the main exception being bone marrow cells) is that its very difficult to get stem cells to exactly where they need to be.

With bone marrow transplants, hematopoietic stem cells naturally “home” (like a missile) to where they need to be (in the blood-making areas of the body). But with other types of stem cells, that is not so readily true, making it difficult or impossible to use the bloodstream as a means of administering stem cell therapies. Of course, you could try to inject, say, heart muscle stem cells directly into the heart, but that’s not only risky/difficult, its also artificial enough that you’re not necessarily providing the heart muscle stem cells with the right triggers/indicators to push them towards becoming normal, functioning heart tissue.

Researchers at Brigham & Women’s Hospital and Mass General Hospital published an interesting approach to this problem in the journal Blood (yes, that’s the real name). They used a unique feature of white blood cells that I blogged about very briefly before called leukocyte extravasation, which lets white blood cells leave the bloodstream towards areas of inflammation.

InflamResponse1

The process is described in the image above, but it basically involves the sugars on the white blood cell’s surface, called Sialyl Lewis X (SLeX), sticking to the walls of blood vessels near sites of tissue damage. This causes the white blood cell to start rolling (rather than flowing through the blood) which then triggers other chemical and physical changes which ultimately leads to the white blood cell sticking to the blood vessel walls and moving through.

imageThe researchers “borrowed” this ability of white blood cells for their mesenchymal stem cells. The researchers took mesenchymal stem cells from a donor mouse and chemically coated them with SLeX – the hope being that the stem cells would start rolling anytime they were in the bloodstream and near a site of inflammation/tissue damage. After verifying that these coated cells still functioned (they could still become different types of cells, etc), they then injected them into mice (who received injections in their ears with a substance called LPS to simulate inflammation) and used video microscopes to measure the speed of different mesenchymal stem cells in the bloodstream. In Figures 2A and 2B to the left, the mesenchymal stem cell coated in SLeX is shown in green and a control mesenchymal stem cell is shown in red. What you’re seeing is the same spot in the ear of a mouse under inflammation with the camera rolling at 30 frames per second. As you can see, the red cell (the untreated) moves much faster than the green – in the same number of frames, its already left the vessel area! That, and a number of other measurements, made the researchers conclude that their SLeX coat actually got their mesenchymal stem cells to slow down near points of inflammation.

But, does this slowdown correspond with the mesenchymal stem cells exiting the bloodstream? Unfortunately, the researchers didn’t provide any good pictures, but they did count the number of different types of cells that they observed in the tissue. When it came to ears with inflammation (what Figure 4A below refers to as “LPS ear”), the researchers saw an average of 48 SLeX-coated mesenchymal stem cells versus 31 uncoated mesenchymal stem cells within their microscopic field of view (~50% higher). When it came to the control (the “saline ear”), the researchers saw 31 SLeX-coated mesenchymal stem cells versus 29 uncoated (~7% higher). Conclusion: yes, coating mesenchymal stem cells with SLeX and introducing them into the bloodstream lets them “home” to areas of tissue damage/inflammation.

image

As you can imagine, this is pretty cool – a simple chemical treatment could help us turn non-bone-marrow-stem cells into treatments you might receive via IV someday!

But, despite the cool finding, there were a number of improvements that this paper needs. Granted, I received it pre-print (so I’m sure there are some more edits that need to happen), but my main concerns are around the quality of the figures presented. Without any clear time indicators or pictures, its hard to know what exactly the researchers are seeing. Furthermore, its difficult to see for sure whether or not the treatment did anything to the underlying stem cell function. The supplemental figures of the paper are only the first step in, to me, what needs to be a long and deep investigation into whether or not those cells do what they’re supposed to – otherwise, this method of administering stem cell therapies is dead in the water.

(Figures from paper) (Image credit: Leukocyte Extravasation)

Paper: Sarkar et al., “Engineered Cell Homing.” Blood. 27 Oct 2011 (online print). doi:10.1182/blood-2010-10-311464

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