Thursday, 21 March 2013

New method for monitoring injected stem cells

Researchers from the Stanford University Medical Centre have developed a new, highly sensitive imaging technique for delivering and monitoring stem cells, with the utmost precision, into the heart. The study has implications in the field of heart tissue regeneration while experimentation on humans is expected within the next 3-5 years.

According to Sam Gambhir, senior author, the previously published literature suggests that heart stem cell infusions to damaged hearts generally yield poor results. However, he says that this is probably the result of faulty initial placement.

"You can use ultrasound to visualise the needle through which you deliver stem cells to the heart. But once those cells leave the needle, you've lost track of them." said Sam Gambhir.

Still, after the injection the fate of stem cells remains largely unknown. Did they pass the heart wall? Did they stay in the injection-location or did they scattered throughout the heart? Did the differentiate into new heart cells? For how long did they survive?

Gambhir says that their technique will help doctors get answers to such questions, as their method not only allows the precise real-time injection of stem cells but also future monitoring.


Image showing the anatomy of human heart
Anatomy of a human heart


"If you inject stem cells into a person and don't see improvement, this technique could help you figure out why and tweak your approach to make the therapy better."

The newly developed technique allows stem cell tracking by marking the cells with a silica-based nanoparticle. Specifically, the nanoparticle can be used for:
  • Cell sorting 
  • Real-time guided cell implantation using ultrasound
  • High-resolution, long-term monitoring with the help of MRI 

During the study it was found that the nanoparticles increased the ultrasound and MRI contrast of human mesenchymal stem cells (hMSCs) by 700% and 200% respectively when compared to unlabelled cells whereas in animals it allowed cell imaging for 13 days following implantation.

The particles have a diameter of less than one-third of a micron (which is equal to one millionth of a meter) or simply put,  less than one-three-thousandth the width of a human hair. The researchers say that the particles are stored and ingested within the MSCs without affecting their capacity to multiply and differentiate into other cells.


A single iPSCs derived heart cell beating


Experiments on mice revealed no toxicity signs with both the control group and the one receiving the MSCs with the ingested nanoparticles behaving similarly. The researchers tried many different types of stem cells including ones taken from mice, human and pigs. 

Jesse Jokerst, chief author, says that they initially were very sceptical. "Because the particles were so small, we weren't expecting much signal strength.But once ingested, the particles clumped together inside the cells, reflecting ultrasound waves much more dramatically and providing a surprisingly strong signal".

According to Gambhir, a stem cell-based treatment for repairing hearts would cost an extra $2,500 if it also included their method. A cost however that would be more than justifiable as it would greatly increases the chances of success.

The scientists believe that their method could be used for delivering stem cells to other organs as well, e.g. the liver.

"This ultrasound-guided cell delivery and multimodal optical/ultrasound/MRI intracardiac cell-tracking platform could improve cell therapy in the clinic by minimising mis-delivery or implantation into fibrotic tissue." extract from the study.


Reference
Jokerst, J., Khademi, C., & Gambhir, S. (2013). Intracellular Aggregation of Multimodal Silica Nanoparticles for Ultrasound-Guided Stem Cell Implantation Science Translational Medicine, 5 (177), 177-177 DOI: 10.1126/scitranslmed.3005228

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