Researchers at Johns Hopkins have devised a way to detect whether cells previously transplanted into a living animal are alive or dead, an innovation they say is likely to speed the development of cell replacement therapies for conditions such as liver failure and type 1 diabetes.
Nanosensors (green spheres) are composed of fat and L-arginine molecules, as well as separate indicator molecules that give off MRI-detectable and light signals when cells are alive. Nanosensors are enclosed in a hydrogel membrane along with liver cells (pink). Nutrients and other relatively small molecules (red) are able to travel across the hydrogel membrane to and from the bloodstream.
Credit: Sayo Studios
As reported in the March issue of Nature Materials, the study used nanoscale pH sensors and magnetic resonance imaging (MRI) machines to tell if liver cells injected into mice survived over time.
"This technology has the potential to turn the human body into less of a black box and tell us if transplanted cells are still alive," says Mike McMahon, Ph.D., an associate professor of radiology at the Johns Hopkins University School of Medicine who oversaw the study. "That information will be invaluable in fine-tuning therapies."
Regenerative medicine advances depend on reliable means of replacing damaged or missing cells, such as injecting pancreatic cells in people with diabetes whose own cells don't make enough insulin. To protect the transplanted cells from the immune system, while allowing the free flow of nutrients and insulin between the cells and the body, they can be encased in squishy hydrogel membranes before transplantation. But, explains McMahon, "once you put the cells in, you really have no idea how long they survive." Such transplanted cells eventually stop working in most patients, who must resume taking insulin. At that point, physicians can only assume that cells have died, but they don't know when or why, says McMahon.
With that problem in mind, McMahon's group, which specializes in methods of detecting chemical changes, collaborated with the research group headed by Jeff Bulte, Ph.D., the director of cellular imaging at Hopkins' Institute for Cell Engineering. Bulte's group devises ways of tracking implanted cells through the body using MRI. Led by research fellow Kannie Chan, Ph.D., the team devised an extremely tiny, or nanoscale, sensor filled with L-arginine, a nutritional supplement that responds chemically to small changes in acidity (pH) caused by the death of nearby cells. Changes in the acidity would in turn set off changes in sensor molecules embedded in the thin layer of fat that makes up the outside of the nanoparticle, giving off a signal that could be detected by MRI.
To test how these nanosensors would work in a living body, the team loaded them into hydrogel spheres along with liver cells — a potential therapy for patients with liver failure — and another sensor that gives off bioluminescent light only while the cells are alive. The spheres were injected just under the skin of mice. As confirmed by the light signal, the MRI accurately detected where the cells were in the body and what proportion were still alive. (Such light indicators cannot be used to track cells in humans because our bodies are too large for visible signals to get through, but these indicators allowed the team to check whether the MRI nanosensors were working properly in the mice.)
"It was exciting to see that this works so well in a living body," Chan says. The team hopes that because the components of the system — hydrogel membrane, fat molecules, and L-arginine — are safe for humans, adapting their discovery for clinical use will prove relatively straightforward. "This should take a lot of the guesswork out of cell transplantation by letting doctors see whether the cells survive, and if not, when they die," Chan says. "That way they may be able to figure out what's killing the cells, and how to prevent it."
Potential applications of the sensors are not limited to cells inside hydrogel capsules, Bulte notes. "These nanoparticles would work outside capsules, and they could be paired with many different kinds of cells. For example, they may be used to see whether tumor cells are dying in response to chemotherapy," he says.
Other authors on the paper were Guanshu Liu, Xiaolei Song, Heechul Kim, Tao Yu, Dian R. Arifin, Assaf A. Gilad, Justin Hanes, Piotr Walczak and Peter C. M. van Zijl, all of the Johns Hopkins University School of Medicine.
The study was funded by the National Institute of Biomedical Imaging and Bioengineering (grant numbers R01 EB012590, EB015031, EB015032 and EB007825).
The paper can be found here: http://www.nature.com/nmat/journal/vaop/ncurrent/abs/nmat3525.html.
Further reading:New Technique Developed for Tracking Cells in the Body: http://www.hopkinsmedicine.org/news/media/releases/New_Technique_Developed
_for_Tracking_Cells_in_the_BodyTracking the Elusive Stem Cell: http://www.hopkinsmedicine.org/stem_cell_research/keeping_track/tracking_
the_elusive_stem_cell.htmlJeff Bulte on Tracking Cells Through the Body: http://www.hopkinsmedicine.org/institute_cell_engineering/experts/meet_
scientists/jeff_bulte.htmlHopkins Imaging Scientist Earns New NIH 'Eureka' Grant for Exceptional, Unconventional Research: http://www.hopkinsmedicine.org/news/media/releases/hopkins_imaging_scientist
Shawna Williams | EurekAlert!
Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View
22.06.2018 | University of Sussex
New cellular pathway helps explain how inflammation leads to artery disease
22.06.2018 | Cedars-Sinai Medical Center
In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.
Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...
Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...
Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.
Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...
The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.
Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.
An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.
Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...
13.06.2018 | Event News
08.06.2018 | Event News
05.06.2018 | Event News
22.06.2018 | Materials Sciences
22.06.2018 | Earth Sciences
22.06.2018 | Life Sciences