A team of researchers from the School of Medicine has created a novel way to image stem cells for transplantation therapies.
The inability to track stem cells after they have been implanted into the body has been a major stumbling block to advancing the medical use of the promising cells.
The problem is simple: How do you know whether the stem cells you have transplanted have actually gone where they were supposed to? If a scientist generates pancreatic cells to treat diabetes, for example, how can she be sure those cells end up in the pancreas?
Live imaging techniques to resolve this dilemma have been unsuccesful to date.
The new technique comes from the laboratories of Martin Pomper and Linzhao Cheng, both professors at the School of Medicine, and is published in Cell Research. It represents a collaborative effort between teams at the Institute for Cell Engineering and the radiology department.
The researchers used two imaging techniques to look at stem cells and how they respond to implantation.
The first is bioluminescent imaging, which uses a super-sensitive camera to measure light emitted in different colors from a specific chemical reaction. Cells can be engineered to express a specific bioluminescent protein that allows visual tracking.
The second is positron emission tomography (PET), which uses the decay of radioactive compounds to monitor the location of chemicals. If cells are treated with these radioactive compounds before injection, they can be traced throughout the body.
Both of these techniques are well-established for use in the medical and scientific communities, making it even easier to incorporate them into future clinical work with stem cells.
This study is known as a "proof-of-principle" study, in which the researchers prove that a concept is feasible and could be used in the future. It has not been tested in humans and is not at the point of clinical trials.
In this study, the researchers used embryonic stem cells to track the formation of teratomas, a conglomeration of many different cell types in a cluster of cells in mice.
The formation of teratomas is actually one of the gold-standard tests for identifying embryonic stem cells. The researchers wanted to see if they could easily and reliably identify stem cells in the body after they had been implanted.
The goal of the study was not to use the stem cells to cure any diseases, but to track them instead. Later this technique could be applied in a therapeutic setting.
Tracking cells is crucial because after implantation, the stem cells will need to be imaged so a physician can observe how the cells are doing inside the body of the patient.
With this in mind, the team altered the embryonic stem cells by adding the bioluminescent gene into one set of embryonic stem cells, and the Herpes Simplex Virus thymidine kinase gene into another set.
The bioluminescent gene, which is found in fireflies, produces a protein that reacts with a certain type of pigment to release light.
Thymidine kinase reacts with radiolabeled compounds to release positrons, charged particles that are picked up by the PET scans. The researchers found that both bioluminescence imaging and PET scans can "see" the stem cells as they proliferate and grow over time. They are also able to track the cell movement in the body.
Also, these methods allow scientists to see the cells before there is even detectable growth, since it usually takes many months for stems cells to form a palpable tumor - a big step forward for stem cells being used in the clinic.
Instead of having to take painful and potentially harmful biopsies, the patients can be imaged harmlessly and repeatedly to monitor the distribution of transplanted stem cells in the body.
With these advances, the hope is that stem cells will reach the clinic sooner and be able to pass Food and Drug Administration approval more rapidly.
