The Faces of Regeneration

Chandan Sen, PhD, who came to IU in August after 18 years at The Ohio State University, is best known for conceiving a technology with the potential to regenerate flesh, restore nerves and regrow organs–all by reprogramming skin cells. It employs a nanochip the size of a dime, perched delicately atop the skin, topped with a drop of genetic material and activated by a split-second jolt of electricity. Sen’s research team has dubbed the process “tissue nanotransfection.” He often refers to it by its abbreviation–TNT. And its implications for the future of health care may just be that explosive. In animals, Sen, a physiologist, has cultivated new blood vessels from skin cells that have returned vitality to injured limbs. TNT has restored function to brains addled by stroke. It has created pancreas-like cells that produce insulin. TNT has even shown direct potential as a tumor therapy—by reprogramming tumor cells so that they shrink. The first applications to reach humans could be to ensure blood flows properly to skin grafts or in helping save limbs otherwise doomed to amputation. But Sen’s work raises other possibilities—that scientists could one day grow new organs to replace old ones. Or, outlandish as it may seem, rescue limbs for soldiers suffering from the devastating injuries of war.

Anantha Shekhar, MD, PhD, who oversees research at IU School of Medicine and helped lure Sen from Ohio State, acknowledges the sci-fi nature of Sen’s work. So does Gayle Gordillo, MD, a plastic surgeon who was Sen’s clinical co-investigator at Ohio State for the last 18 years. Her move to IU precipitated Sen’s.

Yet if Sen’s work sounds like the germ of an H.G. Wells novel, it’s also worth noting it has been published—after rigorous scrutiny—in journals such as Nature Nanotechnology. The National Institutes of Health is in process of awarding grants to fund it. A company based in Hong Kong has licensed it. The government of India wants to host the first human trials. And it was recognized with a silver medal for medical innovations by the prestigious Edison Awards.

IU believes in it enough to pledge $20 million over the next five years to establish a new Indiana Center for Regenerative Medicine and Engineering, with Sen as its inaugural director. IU’s commitment includes bringing Sen, Gordillo and 30-plus scientists and staff here—essentially transplanting the second largest research team at Ohio State to IU.

“I think that’s one of our high risk, high reward kind of bets,” said Shekhar, associate vice president of research for university clinical affairs at IU School of Medicine. “We think that’s an area—tissue engineering, tissue modification, regenerative medicine—that has been a promise for many years. But I think we are at the level of technology where it can now potentially take off.”
Shekhar likens the move toward regenerative medicine to IU’s push, a decade ago, into Alzheimer’s disease research. At the time, he said, Alzheimer’s research seemed like a dead end street. Now, it seems poised for breakthroughs, with IU as a key research hub in the field.

TNT involves a nanochip the size of a dime perched delicately atop the skin, the application of a drop of genetic material and a split-second jolt of electricity.

IN SIMPLEST TERMS, regenerative medicine is a discipline that aims to repair or replace tissues and organs damaged by age, disease or trauma. Interest in this emerging field is growing. Sen’s team brought with it more than $10 million in research grants from Ohio State. Since their arrival, IU has already landed a pair of National Institutes of Health grants seeking to reduce the number of amputations in diabetic patients. NIH has designated IU one of six members of the National Diabetes Foot Consortium, ensuring IU remains at the forefront of wound care research.

IU researchers have been at work in regenerative medicine for some time. Various projects are trying to use stem cells to improve blood flow, repair damaged heart muscle and rebuild structures of the inner ear. There’s an effort underway to modify pig livers for human transplantation. All of this will now be coordinated—and hopefully, boosted—by the Indiana Center for Regenerative Medicine and Engineering.

Sen’s charge is to coalesce the regenerative medicine efforts at IU and build coalitions with industry and other Indiana universities. Sen says this will be crucial since not all of the necessary pieces of the regenerative medicine puzzle exist within the state of Indiana.

Purdue University has the capability to manufacture Sen’s nanochip. It also has some of the “ultraclean” rooms necessary for its production. Sen has also begun reaching out to businesses with unique assets, and many seem eager to help. He says there are professors in Bloomington, and at Notre Dame, who have major contributions to offer, too. But he says more talented researchers are needed.

Usually science takes little baby steps—one on top of the other—but occasionally you get a big jump. And this tissue nanotransfection is a big jump.

“All these remarkable industry and academic assets in regenerative medicine may emerge as a compelling national force if we can synergize them and bring them into one Indiana force,” Sen said.

“All that matters is that as a team we deliver life-changing solutions to our people.”

A native of India who speaks five languages, words gush from Sen like a fountain when it comes to talking about his technology. They flow just as freely when he mentions the names of companies—and countries—he is collaborating with. Sen’s optimism for TNT is unquenchable. “Regenerative Medicine will reshape the way we deliver health care in the future,” Sen said. “There’s no problem in health care that will not be touched by the fruits of regenerative medicine.”

Convinced as he is, Sen is keenly aware that the research is still nascent—that TNT has not yet made it to clinical trials. And that’s his driving motivation. “I will not play that as a huge success,” he said, “until we fix the first human that we want to fix.”

Among those with an interest in his work are people who want to be “fixed.” Since news of TNT hit mainstream media in 2017, Sen has received thousands of emails from people seeking help for loved ones who are disfigured, disabled or dying. “Somebody’s child, somebody’s mother, somebody’s father is sickened in some way and they find an article,” Sen said. “And they are, essentially, for lack of a better word, begging us.” For now, he and his staff must respond with an answer they don’t like to give.

The technology isn’t ready. Not yet.

AT OHIO STATE, Sen blossomed into an international leader in regenerative medicine. For him to come to IU–which had a relatively light footprint in the field–reflects his desire to do expansive research, the importance he places on philanthropic support here and the value he puts in his most trusted collaborator. In fact it was IU’s overture to that friend that began the shift of tectonic plates from Ohio toward Indiana.

Gordillo was a name that came highly recommended to Gary Dunnington, chair of the Department of Surgery at IU School of Medicine, when he was searching for someone to head his Division of Plastic Surgery.

Yet when Dunnington began discussing the job with her, Gordillo made a firm, unexpected declaration.

“I don’t come alone.”

Dunnington had hired people in the past who wanted to bring along others—maybe a PhD or a lab tech. Gordillo wanted much more: Eight or nine PhDs, a biomedical engineer and an array of support staff. All told, the number came to about 35 people. She was a plastic surgeon, yes, but she was convinced the best patient care comes with research going on simultaneously. At the top of her research team wish list was Chandan Sen.

Gordillo and Sen have a unique working relationship.

A native Clevelander, Gordillo has spent most of her life—aside from a few years at Stanford—living in Ohio. Sen grew up in Calcutta, where he conducted some of his early science experiments in his mother’s house, using rats in stacks of cages until she forced a relocation.

Gordillo arrived at Ohio State in 1999 as a clinician who wanted to do more research. Sen arrived in 2000 as a physiologist who desperately wanted to heal people. Over time, they learned to speak the other’s language. They grew to trust each other intuitively—almost to the point they can speak for one another.

“There has to be a mutual level of trust,” Gordillo said. “He has his wife Sashwati (Roy), but it’s almost like a marriage. I would say that about my clinical partners as well. You have to trust each other. You have to cover each other’s back.”

Regenerative medicine is a very broad field with huge upside potential. I do think the day will come where we can regrow some organs, such as the liver or endocrine pancreas,” Hess said. “It is critically important to be scientifically rigorous, ensuring we are always looking out for the patients’ best interests and ensure we are not overselling what we do.

Both realized that kind of professional relationship was rare. Neither was interested in ending it. Sen had once considered a move a few years ago. The pair agreed Gordillo would go, too. But both loved being at Ohio State and the move didn’t happen. When IU called Gordillo, their arrangement was still in place. The question was whether IU would agree to bring along the whole research family.

Dunnington’s first choice was simple: He could move to the next candidate on his list of plastic surgeons or head to Fairbanks Hall to give Shekhar and IU School of Medicine Dean Jay Hess the biggest sales pitch of his career. “Jay and Anantha have been saying all along–we’re looking for visionary people, we’re recruiting really world class scientists,” Dunnington said. “When I made the trip over there I said let’s see if they really mean that or not.”

They meant it.

“We are always looking for opportunities to recruit top talent and create programs that will have a national impact, said Hess, MD, PhD, MHSA. “The first thing we had to do was learn more about Dr. Sen, his track record and his ideas.”

There had been discussions of building a program in regenerative medicine at IU, Hess said. But this was a different kind of opportunity.

“Regenerative medicine is a very broad field with huge upside potential. I do think the day will come where we can regrow some organs, such as the liver or endocrine pancreas,” Hess said. “It is critically important to be scientifically rigorous, ensuring we are always looking out for the patients’ best interests and ensure we are not overselling what we do.”

Aside from the arrangement with Gordillo, Sen still needed some convincing. Upon subsequent visits to Indianapolis, he got it. Gordillo would play a prominent role in the IU Health System’s wound center. The hospital’s statewide access to patients would offer a broad base for research.

Equally important was the School of Medicine’s philanthropic base. Ohio State was one of seven medical schools in the Buckeye State, each competing for philanthropic dollars. Indiana’s setup—a single, public medical school with a statewide footprint—engenders broad and substantial support for research. That’s crucial in a field such as regenerative medicine, where the most innovative discoveries are often too risky for industry to back. Government grants are drawn narrowly to accomplish specific tasks, leaving little room for open-ended, high-risk research.

“The question is where is that next idea coming from and who is going to fund it,” Gordillo said. “That’s what philanthropy does.”

At Ohio State, Sen had numerous grants to fund day-to-day projects at his lab. But it took a $1.5 million gift from a private donor to give him the room for the experimentation that lead to the TNT technology.

“I decided to dedicate that gift to this very risky project—the chip part,” Sen said. “That part was never funded by anybody in government or industry because I wouldn’t write a grant on it because it is unbelievable.”

The payoff—in the form of tissue nanotransfection—could be huge. Sen wants to dramatically reduce Indiana’s high number of limb amputations, which are often a complication of diabetes. That may be only the beginning.

“Usually science takes little baby steps—one on top of the other—but occasionally you get a big jump,” Gordillo said. “And this tissue nanotransfection is a big jump.”

Where his research could lead is almost too hard to grasp. But Sen knows he doesn’t want to play things safe. He wants to take risks, even if he fails. At 52, the research scientist even has a bit of a philosopher at work within.

“I’m looking at the closure of my professional career—it is not infinite. I can see it. There was a time when I never thought about it. I do now. What is a successful career?”

If it were just about getting more grants and publishing more papers, he would be miserable, he says.

“I want to leave a legacy of health care impact to inspire others. I want to subscribe to a grander vision,” he said. “And that’s where the beauty is. That’s what keeps me going.”