How to Keep Cancer from Returning after Surgery

After surgery to remove tumors, some cancer cells can be left behind where they can grow back or spread to a new part of the body. Researchers at the University of Wisconsin-Madison have now developed a hydrogel that can be applied post-surgery to prevent or slow tumor regrowth. The gel works by releasing two compounds selected to strategically keep cancer from coming back after surgery. First is a drug called Pexidartinib, which is already in use to inhibit tumor-associated macrophages (TAMs). These are immune cells that have, for unclear reasons, “switched sides” and now contribute to creating a pro-cancer environment. As such, inhibiting these TAMs slows the growth (or regrowth) of cancer.

A microscope image of the hydrogel (teal) containing platelets with antibodies (red) and tumor-fighting drug nanoparticles (green)

The second component is made up of PD-1 antibodies, which help train T cells to recognize and attack cancer cells. These are bound to platelets for stability. Together, the two components prevent the formation of a microenvironment that’s favorable to cancer growth, and help the immune system clear out any cancer cells remaining after surgery. After its work is done, the gel is designed to biodegrade safely in the body.

The researchers tested the gel in mouse models of several different types of cancers, including colon cancer, melanoma, sarcoma, and triple negative breast cancer. The gel significantly reduced recurrence and metastasis of the cancer, and extended the survival rates of the mice – all control animals succumbed within 36 days, while survival rates ranged between 50 and 66 percent for treated mice, depending on the type of cancer.

The local application of the gel also helps prevent side effects that can arise if a drug is delivered system-wide. As such, no major side effects were seen in the test mice. Importantly, the team says that some of these cancers don’t usually respond well to immune therapy, and are prone to metastasizing, so the effectiveness of the gel treatment is encouraging.

We are really glad to see that this local strategy can work against so many different kinds of tumors, especially these non-immunogenic tumors,” said Quanyin Hu, lead researcher on the study. “We are even more glad to see this local treatment can inhibit tumor metastasis.”


How to Reverse Parkinson’s Symptoms

Grafting neurons grown from monkeys’ own cells into their brains relieved the debilitating movement and depression symptoms associated with Parkinson’s disease, researchers at the University of Wisconsin–Madison (UW) reported today.

In a study published in the journal Nature Medicine, the UW team describes its success with neurons made from induced pluripotent stem cells from the monkeys’ own bodies. This approach avoided complications with the primates’ immune systems and takes an important step toward a treatment for millions of human Parkinson’s patients.

This result in primates is extremely powerful, particularly for translating our discoveries to the clinic,” says UW–Madison neuroscientist Su-Chun Zhang, whose lab grew the brain cells.

Parkinson’s disease damages neurons in the brain that produce dopamine, a brain chemical that transmits signals between nerve cells. The disrupted signals make it progressively harder to coordinate muscles for even simple movements and cause rigidity, slowness and tremors that are the disease’s hallmark symptoms. Patients — especially those in earlier stages of Parkinson’s — are typically treated with drugs like L-DOPA to increase dopamine production.

Those drugs work well for many patients, but the effect doesn’t last,” says Marina Emborg, a Parkinson’s researcher at UW–Madison’s Wisconsin National Primate Research Center. “Eventually, as the disease progresses and their motor symptoms get worse, they are back to not having enough dopamine, and side effects of the drugs appear.”

Scientists have tried with some success to treat later-stage Parkinson’s in patients by implanting cells from fetal tissue, but research and outcomes were limited by the availability of useful cells and interference from patients’. Zhang’s lab has spent years learning how to dial donor cells from a patient back into a stem cell state, in which they have the power to grow into nearly any kind of cell in the body, and then redirect that development to create neurons.

The idea is very simple,” Zhang says. “When you have stem cells, you can generate the right type of target cells in a consistent manner. And when they come from the individual you want to graft them into, the body recognizes and welcomes them as their own.


Nanoparticles Act As Immunotherapy Agents

University of Wisconsin–Madison researchers have developed nanoparticles that, in the lab, can activate immune responses to cancer cells. If they are shown to work as well in the body as they do in the lab, the nanoparticles might provide an effective and more affordable way to fight cancer.

They are cheaper to produce and easier to engineer than the antibodies that underlie current immunotherapies, which as drugs cost tens of thousands of dollars a month.

The nanoparticles were made of sections of the T cell protein PD-1 (in blue) attached to a branched core called a dendrimer (in gray). The branches in the core of the nanoparticle allowed many chunks of the PD-1 protein to bind to the nanoparticle, increasing its effectiveness.

Immunotherapy basically boosts the patient’s own immune system to fight against cancer cells better,” says Seungpyo Hong, a professor in the UW–Madison School of Pharmacy. “The antibodies that are used right now are large, they’re expensive, they’re hard to engineer, and they don’t always show the highest level of efficacy either. So we wanted to explore other ways to activate the immune system.

Hong and postdoctoral associate Woo-jin Jeong led the study, published online Jan. 2 in the Journal of the American Chemical Society, with collaborators at the University of Illinois at Chicago. It’s the first demonstration that nanoparticles can act as immunotherapy agents.

More research is needed to understand their effectiveness in the body, but Hong has applied for a patent on the new nanoparticles and is now testing them in animal models.

In tests against lab-grown strains of cancer, the nanoparticles boosted production of the immune stimulating protein interleukin-2 by T cells, one kind of immune cell in the body, by about 50 percent compared to no treatment. They were just as effective as antibodies. The nanoparticles were also able to improve the effectiveness of the chemotherapy drug doxorubicin in similar tests.

Normally, T cells produce a protein named PD-1 that acts like an off switch for immune responses. This “checkpoint” helps keep T cells from improperly attacking healthy cells.


How To Reverse Baldness Using Nanogenerators

Few things on earth strike fear into the hearts of men more profoundly than hair loss. But reversing baldness could someday be as easy as wearing a hat, thanks to a noninvasive, low-cost hair-growth-stimulating technology developed by engineers at the University of Wisconsin–Madison (UW Madison).

I think this will be a very practical solution to hair regeneration,” says Xudong Wang, a professor of materials science and engineering at UW–Madison.

Based on devices that gather energy from a body’s day-to-day motion, the hair-growth technology stimulates the skin with gentle, low-frequency electric pulses, which coax dormant follicles to reactivate hair production. The devices don’t cause hair follicles to sprout anew in smooth skin. Instead they reactivate hair-producing structures that have gone dormant. That means they could be used as an intervention for people in the early stages of pattern baldness, but they wouldn’t bestow cascading tresses to someone who has been as bald as a billiard ball for several years.

Because the devices are powered by the movement of the wearer, they don’t require a bulky battery pack or complicated electronics. In fact, they’re so low-profile that they could be discreetly worn underneath the crown of an everyday baseball cap. Wang is a world expert in the design and creation of energy-harvesting devices. He has pioneered electric bandages that stimulate wound-healing and a weight-loss implant that uses gentle electricity to trick the stomach into feeling full.

The hair-growth technology is based on a similar premise: Small devices called nanogenerators passively gather energy from day-to-day movements and then transmit low-frequency pulses of electricity to the skin. That gentle electric stimulation causes dormant follicles to “wake up.” “Electric stimulations can help many different body functions,” says Wang. “But before our work there was no really good solution for low-profile devices that provide gentle but effective stimulations.”

Wang and colleagues published a description of the technology in the journal ACS Nano.


Electricity Speeds Up Skin Healing

A new, low-cost wound dressing developed by University of Wisconsin–Madison engineers could dramatically speed up healing in a surprising way. The method leverages energy generated from a patient’s own body motions to apply gentle electrical pulses at the site of an injury. In rodent tests, the dressings reduced healing times to a mere three days compared to nearly two weeks for the normal healing process.

“We were surprised to see such a fast recovery rate,” says Xudong Wang, a professor of materials science and engineering at UW–Madison.We suspected that the devices would produce some effect, but the magnitude was much more than we expected.

Researchers have known for several decades that electricity can be beneficial for skin healing, but most electrotherapy units in use today require bulky electrical equipment and complicated wiring to deliver powerful jolts of electricity.  “Acute and chronic wounds represent a substantial burden in healthcare worldwide,” says collaborator Angela Gibson, professor of surgery at UW–Madison and a burn surgeon and director of wound healing services at UW Health. “The use of electrical stimulation in wound healing is uncommon.” In contrast with existing methods, the new dressing is much more straightforward. “Our device is as convenient as a bandage you put on your skin,” says Wang. “The nature of these electrical pulses is similar to the way the body generates an internal electric field,” explains Wang.

Wang and collaborators described their wound dressing method in the journal ACS Nano.


How To Heal Acute Kidney Injury

Each year, there are some 13.3 million new cases of acute kidney injury (AKI), a serious affliction. Formerly known as acute renal failure, the ailment produces a rapid buildup of nitrogenous wastes and decreases urine output, usually within hours or days of disease onset.  Severe complications often ensue. Currently, there is no known cure for AKI.

AKI is responsible for 1.7 million deaths annually. Protecting healthy kidneys from harm and treating those already injured remains a significant challenge for modern medicine.

In new research appearing in the journal Nature Biomedical Engineering, Hao Yan and his colleagues at the University of Wisconsin-Madison and in China describe a new method for treating and preventing AKI. Their technique involves the use of tiny, self-assembling forms measuring just billionths of a meter in diameter.

Yan directs the Biodesign Center for Molecular Design and Biomimetics and is Professor in the School of Molecular Sciences at the Arizona State University (ASU).

Their research demonstrated that the introduction of DNA origami nanostructures (DONs) protected normal kidneys and improved functioning of kidneys damaged by AKI. The beneficial effect of the nanostructures was comparable to the current treatment modality, administration of an anti-oxidant drug known as N-acetylcysteine (NAC). New treatments are being saught because NAC is not easily absorbed in the kidneys. Further examination of stained tissue samples from mice confirmed the beneficial effects of the DONs.