Tag Archives: Yi Xuan

Treating traumatic muscle loss with tissue nanotransfection

A November 9, 2022 news item on ScienceDaily announces some work from Indiana University (US),

Technology developed by researchers at the Indiana University School of Medicine that can change skin tissue into blood vessels and nerve cells has also shown promise as a treatment for traumatic muscle loss.

Tissue nanotransfection is a minimally invasive nanochip device that can reprogram tissue function by applying a harmless electric spark to deliver specific genes in a fraction of a second.

A November 9, 2022 Indiana University news release (also on EurekAlert), which originated the news item, provides additional technical details, Note: Links have been removed,

A new study, published in Nature Partner Journals Regenerative Medicine, tested tissue nanotransfection-based gene therapy as a treatment, with the goal of delivering a gene known to be a major driver of muscle repair and regeneration. They found that muscle function improved when tissue nanotransfection was used as a therapy for seven days following volumetric muscle loss in rats. It is the first study to report that tissue nanotransfection technology can be used to generate muscle tissue and demonstrates its benefit in addressing volumetric muscle loss.

Volumetric muscle loss is the traumatic or surgical loss of skeletal muscle that results in compromised muscle strength and mobility. Incapable of regenerating the amount of lost tissue, the affected muscle undergoes substantial loss of function, thus compromising quality of life. A 20 percent loss in mass can result in an up to 90 percent loss in muscle function.

Current clinical treatments for volumetric muscle loss are physical therapy or autologous tissue transfer (using a person’s own tissue), the outcomes of which are promising but call for improved treatment regimens.

“We are encouraged that tissue nanotransfection is emerging as a versatile platform technology for gene delivery, gene editing and in vivo tissue reprogramming,” said Chandan Sen, director of the Indiana Center for Regenerative Medicine and Engineering, associate vice president for research and Distinguished Professor at the IU School of Medicine. “This work proves the potential of tissue nanotransfection in muscle tissue, opening up a new avenue of investigational pursuit that should help in addressing traumatic muscle loss. Importantly, it demonstrates the versatility of the tissue nanotransfection technology platform in regenerative medicine.”

Sen also leads the regenerative medicine and engineering scientific pillar of the IU Precision Health Initiative and is lead author on the new publication.

The Indiana Center for Regenerative Medicine and Engineering is home to the tissue nanotransfection technology for in vivo tissue reprogramming, gene delivery and gene editing. So far, tissue nanotransfection has also been achieved in blood vessel and nerve tissue. In addition, recent work has shown that topical tissue nanotransfection can achieve cell-specific gene editing of skin wound tissue to improve wound closure.

Here’s a link to and a citation for the paper,

Myogenic tissue nanotransfection improves muscle torque recovery following volumetric muscle loss by Andrew Clark, Subhadip Ghatak, Poornachander Reddy Guda, Mohamed S. El Masry, Yi Xuan, Amy Y. Sato, Teresita Bellido & Chandan K. Sen. npj Regenerative Medicine volume 7, Article number: 63 (2022) DOI: https://doi.org/10.1038/s41536-022-00259-y Published: 20 October 2022

This paper is open access.

This is a very nice image of a delighted Dr. Sen,

Caption Chandan Sen Credit: Photo by Liz Kaye, Indiana University

Tissue nanotransfection

I’m wondering how I missed the research from last year (2021) which foregrounds this latest work. Ah well. It happens. Making up for lost time, here’s a July 18, 2022 news item on phys.org about tissue nanotransfection, Note: Links have been removed,

The Indiana Center for Regenerative Medicine and Engineering (ICRME) at Indiana University School of Medicine is home to tissue nanotransfection (TNT) regenerative medicine technology that achieves functional tissue reprogramming in the live body. Last year, ICRME researchers published on how to manufacture the TNT 2.0 silicon chip hardware in Nature Protocol. Now, their research demonstrates for the first time that TNT can serve as a non-viral, topical gene-editing delivery device.

TNT is a minimally invasive device that can reprogram tissue function in the live body by applying pulses of harmless, electric sparks to deliver specific genes of interest to the skin.

“TNT-based delivery can achieve cell-specific gene editing,” said corresponding author Chandan K. Sen, Ph.D., the J. Stanley Battersby Chair and distinguished professor of surgery, director of the ICRME at IU School of Medicine and executive director of the Indiana University Health Comprehensive Wound Care Center. “Your skin has thousands of genes and in chronic wounds many key genes are silenced by DNA methylation. TNT-based gene editing technology can remove that barrier.”

A July 18, 2022 Indiana University School of Medicine news release (also on EurekAlert), which originated the news item, updates the information with some of the latest research, Note: Links have been removed,

In this study, genome-wide methylation was observed in the chronic wound tissue of patients. This was reproduced in an experimental murine model. TNT-based, cell-specific gene editing rescued wound healing. Results were published recently [July 12, 2022] in the Journal of Clinical Investigation.

Previous TNT application studies reported on the rescue of injured legs, diabetic neuropathy, crushed nerve and the stroke-affected brain. This is the first time promoter methylation of genes is recognized as a critical barrier to wound healing. In this study, ICRME investigators found that P53 methylation and gene silencing as a critical barrier to cutaneous wound epithelial-to-mesenchymal transition (EMT), a mechanism that is necessary to close skin wounds. TNT based non-viral keratinocyte-specific demethylation of P53 gene rescued EMT and achieved wound closure.

Chronic wounds can result in serious and sometimes life-threatening complications from an abundance of dying and necrotic tissue, such as cellulitis, lower-extremity amputation and sepsis. Treating chronic wounds is estimated to cost the United States health care system $28 billion annually, which amplifies the need to test novel treatments to prevent amputation, save lives and lower health care costs.

“Inspired by observations in chronic wound patients, this work has achieved an important milestone highlighting the need to de-silence genes at the wound-site,” said first author Kanhaiya Singh, PhD, assistant professor of surgery and an investigator at the ICRME.

Here are two links and citations. First, the earlier work,

Fabrication and use of silicon hollow-needle arrays to achieve tissue nanotransfection in mouse tissue in vivo by Yi Xuan, Subhadip Ghatak, Andrew Clark, Zhigang Li, Savita Khanna, Dongmin Pak, Mangilal Agarwal, Sashwati Roy, Peter Duda & Chandan K. Sen. Nature Protocols volume 16, pages 5707–5738 (2021) DOI: https://doi.org/10.1038/s41596-021-00631-0 Published: 26 November 2021 Issue Date: December 2021

This paper is behind a paywall.

Now, the latest work

Genome-wide DNA hypermethylation opposes healing in chronic wound patients by impairing epithelial-to-mesenchymal transition by Kanhaiya Singh, Yashika Rustagi, Ahmed S. Abouhashem, Saba Tabasum, Priyanka Verma, Edward Hernandez, Durba Pal, Dolly K. Khona, Sujit K. Mohanty, Manishekhar Kumar, Rajneesh Srivastava, Poornachander R Guda, Sumit S. Verma, Sanskruti Mahajan, Jackson A. Killian, Logan A. Walker, Subhadip Ghatak, Shomita S. Mathew-Steiner, Kristen Wanczyk, Sheng Liu, Jun Wan, Pearlly Yan, Ralf Bundschuh, Savita Khanna, Gayle M. Gordillo, Michael P. Murphy, Sashwati Roy, and Chandan K. Sen. J Clin Invest. DOI: https://doi.org/10.1172/JCI157279 Published: July 12, 2022 Version 1 (In-Press Preview) Version 2: J Clin Invest. 2022;132(17):e157279. https://doi.org/10.1172/JCI157279. Volume 132, Issue 17 Published September 1, 2022

This paper is open access.