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Converting skin to blood vessels in a single touch

A breakthrough device converts skin to blood vessels by delivering new DNA or RNA into living skin cells, thus changing their function.


Researchers at The Ohio State University Wexner Medical Center and Ohio State's College of Engineering have developed new technology, Tissue Nanotransfection (TNT), which can regenerate any cell type (in their test case, skin cells) for treatment within a patient's own body. Their success with mice suggests the technology can be used to repair injured tissue or restore function in aging tissue, including organs, blood vessels and nerve cells, according to the researchers.
In lab tests, TNT was also shown to reprogram skin cells in a live mouse into nerve cells that were then injected into brain-injured mice to help them recover from stroke.

Results of their regenerative medicine study are published in the journal Nature Nanotechnology.
Researchers used mice and pigs in their experiments.

Working with mice to recover injured legs with damaged blood flow, the scientists reprogrammed mouse skin cells around the injury site to become vascular or blood vessel cells by administering their TNT or single touch technology. Within one week, active blood vessels appeared in the injured leg, by the second week leg blood vessel recovery saved the leg from amputation.

"By using our novel nanochip technology, injured or compromised organs can be replaced. We have shown that skin is a fertile land where we can grow the elements of any organ that is declining," said Dr. Chandan Sen, director of Ohio State's Center for Regenerative Medicine & Cell Based Therapies, who co-led the study with L. James Lee, professor of chemical and biomolecular engineering with Ohio State's College of Engineering in collaboration with Ohio State's Nanoscale Science and Engineering Center.
"This is difficult to imagine, but it is achievable, successfully working about 98 percent of the time. With this technology, we can convert skin cells into elements of any organ with just one touch. This process only takes less than a second and is non-invasive, and then you're off. The chip does not stay with you, and the reprogramming of the cell starts. Our technology keeps the cells in the body under immune surveillance, so immune suppression is not necessary,"

Chandan K. Sen, Department of Surgery, Ohio State University, Director, Center for Regenerative Medicine and Cell-Based Therapies, The Ohio State University, Columbus, Ohio, USA


TNT technology has two major components: First a nanotechnology-based chip designed to deliver cargo to adult cells in the live body. Second the design of specific biological cargo for cell conversion. This cargo, when delivered using the chip, converts an adult cell from one type to another, explains first author Daniel Gallego-Perez, an assistant professor of biomedical engineering and general surgery who also began his postdoctoral research in both Sen's and Lee's laboratories.
TNT doesn't require any laboratory-based procedures and may be implemented at the point of care. The procedure is also non-invasive. The cargo is delivered by zapping the device with a small electrical charge that's barely felt by the patient.

"The concept is very simple," Lee said. "As a matter of fact, we were even surprised how it worked so well. In my lab, we have ongoing research trying to understand the mechanism and do even better. So, this is the beginning, more to come."

Sen and his team plan to start clinical trials next year to test this technology in humans.

Abstract
Although cellular therapies represent a promising strategy for a number of conditions, current approaches face major translational hurdles, including limited cell sources and the need for cumbersome pre-processing steps (for example, isolation, induced pluripotency)1, 2, 3, 4, 5, 6. In vivo cell reprogramming has the potential to enable more-effective cell-based therapies by using readily available cell sources (for example, fibroblasts) and circumventing the need for ex vivo pre-processing7, 8. Existing reprogramming methodologies, however, are fraught with caveats, including a heavy reliance on viral transfection9, 10. Moreover, capsid size constraints and/or the stochastic nature of status quo approaches (viral and non-viral) pose additional limitations, thus highlighting the need for safer and more deterministic in vivo reprogramming methods11, 12. Here, we report a novel yet simple-to-implement non-viral approach to topically reprogram tissues through a nanochannelled device validated with well-established and newly developed reprogramming models of induced neurons and endothelium, respectively. We demonstrate the simplicity and utility of this approach by rescuing necrotizing tissues and whole limbs using two murine models of injury-induced ischaemia.

All authors: Daniel Gallego-Perez, Durba Pal, Subhadip Ghatak, Veysi Malkoc, Natalia Higuita-Castro, Surya Gnyawali, Lingqian Chang, Wei-Ching Liao, Junfeng Shi, Mithun Sinha, Kanhaiya Singh, Erin Steen, Alec Sunyecz, Richard Stewart, Jordan Moore, Thomas Ziebro, Robert G. Northcutt, Michael Homsy, Paul Bertani, Wu Lu, Sashwati Roy, Savita Khanna, Cameron Rink, Vishnu Baba Sundaresan, Jose J. Otero, L. James Lee and Chandan K. Sen

Keywords: Nanofabrication and nanopatterning Tissue engineering and regenerative medicine


Funding for this research was provided by Leslie and Abigail Wexner, Ohio State's Center for Regenerative Medicine and Cell-Based Therapies and Ohio State's Nanoscale Science and Engineering Center.

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Aug 14, 2017   Fetal Timeline   Maternal Timeline   News   News Archive




TOP - Missing blood vessels (circled in red) in injured mouse leg
BOTTOM - Blood vessels (circled in red) grow after TNT repair.
Image credit: Ohio State University, Wexner Medical Center



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