The stem cells are introduced inside the heart after an attack to reprimand the damaged tissues of the heart. The promise of repairing damaged hearts through regenerative therapy, i.e. infusing stem cells into the heart in the hope that these cells will replace the worn out or damaged tissue has yet to meet with the screening techniques of the clinical trial. The researchers and qualified medical professionals of Stanford University School of Medicine are trying to develop a highly sensitive visualization technique which may help in accelerating the dream of repairing the damaged heart's tissue with stem cells into realization.

Several trials have been performed on animals and humans in which stem cells were injected into the cardiac tissue to treat the acute heart attack or substantial heart failure but in vain. The results of the trials were inefficient for the approval of the therapy. The poor results are partly due to faulty initial placement. The ultrasound can be used to visualize the needle through which the stem cells are delivered into the heart. But once those cells leave the needle, their track is lost. As a result, we are still unaware about the fact that whether the stem cells actually get to the heart wall and if they did, did they stay there, or just get diffused away from the heart. The key problem still remains unanswered that if they got into the heart wall remained there then for how long these cells were alive and whether they replicate and develop into the heart tissue, thus, repairing the damaged heart tissue. If these key questions are solved, we can attain success in developing the regenerative therapy for the healthy life of our hearts.Even the initial positioning of the therapeutic stem cells is vague and unknown. There is no sign to distinguish these cells from other cells in the patient's body, so once released from the needle tip they can't be tracked afterward. If, in the coming weeks, the beating rhythm or pumping prowess of the heart has failed to improve after the infusion of stem cells into the heart, it is impossible for the doctors to detect the reason. This ambiguity, perpetuated by the absence of decent imaging tools, stifles researchers' ability to optimize their therapeutic approach.

All the scientists and researchers who wanted to hit the stem cells into the target site but have shot blindly would be much relieved now with the development of molecular imaging tool. With this new approach, for the first time ever, the researchers would be able to observe in real time the exact position of stem cells into the heart wall monitor their track for the whole journey. If the stem cells injected into the heart of a person is not showing any improvement, then this technique could help us in figuring out the problem and giving new approaches to make the therapy better. The new technology employs a trick that marks the stem cells so that they can be tracked by the standard ultrasound machine as they are squeezed out of the needle. This allows a more precise guidance to the spot where they are intended to go, and then they are monitored by magnetic-resonance imaging for judging their therapy.

To make this technology into a reality, the scientists designed and produced a specialized imaging agent in the form of nano-particles whose diameters clustered in the vicinity of just below one-third of a micron, less than one-three-thousandth the width of a human hair, or one-thirtieth the diameter of a red blood cell. The acoustical characteristics of the chief constituents of these nanoparticles, i.e. silica, helped them to be visualized by the ultrasound. They were also doped with the rare-earth element gadolinium, which is an MRI contrast agent. This designing and development was done at Stanford University. The group of discoverers showed that the mesenchymal stem cells, a class of stem cells often used in heart-regeneration research, were able to ingest and store the nanoparticles without losing any of their ability to survive, replicate and differentiate into the living heart cells. The mesenchymal stem cells can differentiate the beating heart cells. These cells can sometimes be harvested from the patients who is about to undergo the treatment. This could, in principle, alleviate concerns about the cells being rejected by a patient's immune system. Thus, the nanoparticles were impregnated with a fluorescent material, so the research team could determine which mesenchymal stem cells gobbled them up.

Upon infusing the imaging-agent-loaded stem cells from mice, pigs or humans into the hearts of healthy mice, the scientists were able to observe the cells via ultrasound after they left the needle tip and, therefore, better direct them to the targeted area of the heart wall. After certain period of time, the researchers could still get a strong MRI signal from the cells. Eventually, the continued division of the healthy infused stem cells diluted the signal to below the MRI detection limit.

The discovery of nanoparticles was proved to be worthy. Earlier there was some confusion about efficiency and efficacy of this technique. As the particles were really small (nano size), their signal strength were expected to be low. But once ingested, the particles clumped together inside the cells, reflecting ultrasound waves much more dramatically and providing a surprisingly strong signal as well. Using this nano particle, the doctors and investigators were able to detect as few as 70,000 of the stem cells by ultrasound and as few as 250,000 by MRI. But this number is very small in comparison to the tens or hundreds of millions of stem cells being infused into human hearts in clinical trials these days.

There was no sign of toxicity or behavioural differences observed in the mice receiving the agent-containing stem cells when compared with the control animals receiving stem cells without the agent. These nanoparticles are now approved by the U.S. Food and Drug Administration (FDA) for other applications as well. Even silicon is considered to be relatively non-toxic and are being in the clinics. Gadolinium, the rare earth element, which can be toxic at high doses, is clinically approved by the FDA in doses much greater than would be necessary for this new imaging procedure, even if hundreds of millions of stem cells were involved.

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Geetanjali Murari
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