Tag Archives: Graft

Insulin injection.

Stem-cell implant prototypes pave the way towards life-long treatment for type 1 diabetes

New research is paving the way towards reliable, long-term treatments for type 1 diabetes. The work focused on developing implants based on stem cells that can deliver insulin directly into the bloodstream of diabetes patients.

Insulin injection.
Image credits Peter Stanic.

While the implants are not yet ready for use in a clinical role, the research does prove the viability of such systems for use in the future. The implants consist of pancreatic endoderm cells derived from human pluripotent stem cells (PSCs) and were tested with 26 patients. After more research and development, once such implants become able to secrete levels of insulin that will have a clinical effect on their recipients, they could become a viable alternative to current insulin-delivery systems and islet replacement therapies (pancreatic transplants).

Promising first steps

“The device is band-aid sized and designed to contain the lab grown islet cells for subcutaneous implant. It allows the cells within to become vascularized to permit delivery of oxygen and nutrients and release of insulin into the bloodstream. It is also readily retrievable”, said Dr. Timothy J. Kieffer of the University of British Columbia, corresponding author of the study, for ZME Science.

The team aims to provide an unlimited supply of insulin-producing cells for patients with type 1 diabetes, to mediate continuous, long-term treatment options while minimizing the invasiveness of the procedure.

Insulin is a hormone that keeps the levels of glucose (sugar) in our blood under control, and is produced by pancreatic β-cells. Type 1 diabetes is characterized by the destruction of these cells and leads to dangerously high levels of glucose building up in patients’ bloodstreams. Current treatments for this condition involve the administration of insulin directly into the bloodstream, either via manual injection or through automated systems that a patient can wear, which deliver the hormone periodically. Another possibility — although seen much more rarely in the grand scheme of things — is to treat the condition through islet transplant from donor organs.

Each of these treatment options comes with its own drawbacks. Direct injections require users to monitor their own state, remember to perform the procedure, and also carry the risk that they administer the shots imperfectly. Automated devices can be very burdensome to wear for long periods of time, are associated with long-term complications, and can malfunction. Transplants are very intrusive procedures and the supply of donor organs is very limited compared to the demand.

As such, an alternative is required, the team argues.

The current study reports on a phase I/II clinical trial involving the use of pancreatic endoderm cells as one such alternative. The team’s devices contain such cells in special capsules that allow for direct vascularization of the cells; these were implanted under the skin of the patients. The procedure did, however, run the risk of the participants’ bodies rejecting the implants, and thus involved an immunosuppressive treatment regimen that is commonly used in donor islet transplantation procedures. Possible side-effects of such treatments is an increased risk of cancer and infections in patients, as a direct consequence of their immune systems being suppressed.

That being said, the authors report that the devices worked as intended, and the cells within them started secreting insulin and delivering it directly into the participants’ bloodstreams in response to the glucose levels in their blood. Insulin expression (secretion) was recorded in 63% of the devices after they were explanted at time periods between 3 and 12 months after implantation. Insulin-secreting cells started accumulating progressively in these devices over a period of between 6 and 9 months after implantation.

Although not yet able to cover their full requirements for insulin, over a one-year study period, they reduced the amount of insulin participants needed to be administered by 20%. They also spent 13% more time in the target blood glucose range compared to pre-study periods.

“We found the implants were able to produce insulin in a meal regulated manner like normal healthy pancreatic islets, albeit at low levels,” Dr. Kieffer adds for ZME Science. “The sponsor company ViaCyte recently reported achieving clinically meaningful levels of insulin when more of these devices were implanted (8) that resulted in a dramatic reduction in the insulin injection requirements accompanied by vastly improved control of blood sugar.”

Overall, these devices were well-tolerated by their bodies and there were no severe adverse effects caused by the grafts. Two participants did experience serious adverse effects related to the immunosuppression treatment. Most of the adverse effects reported by participants, however, were related to the actual implantation/explantation surgeries, or to side-effects of the immunosuppressive treatment. All things considered, the team explains, the risk of local infection posed by the devices was very low, suggesting that the devices themselves are well-tolerated even in participants with a poor immune or healing response.

This does raise questions regarding the use of such devices over a patient’s whole life. An ideal solution to this would be an option to perform stem cell-based islet replacement therapy without the devices themselves, as this would bypass the need for immunosuppressive treatments altogether.

Still work to be done

One of the major limitations of the study was the lack of a control group, so the findings should not be used to draw any conclusion on how effective such devices would be at treating type 1 diabetes. However, the study does show that they are relatively safe to use and validate the working principle behind their design. More research will be needed to determine the quantity of cells such implants should contain in order to produce clinically-relevant benefits for patients.

“It was very exciting to see clear meal regulated insulin production in patients following the implants and also see islet cells in the retrieved devices that looked like normal healthy pancreatic islet cells. We now have clear proof of principle data that this stem cell-based approach can work,” Dr. Kieffer adds for ZME Science.

Currently, the cells survive an average of 59 weeks after implantation. The total percentage of insulin-positive cells they contained at maturation was below the team’s ideal target, however. The researchers are now working on solutions to promote vascularization between the grafts and the patients’ bodies, and on measures to improve the survival of the cells they contain.

“Our ultimate goal is to entirely free patients from the burden of glucose monitoring and insulin injections, and without the use of any immunosuppression,” Dr. Kieffer concluded in his email for ZME Science. “We are thus very excited by the recent ViaCyte / CRISPR Therapeutics announcement that Health Canada has approved clinical testing of genetically modified cells that have been engineered to evade detection by the immune system.”

“With protocol refinements and immune-evasive cells, we hope to reach this goal.

The paper “Implanted pluripotent stem-cell-derived pancreatic endoderm cells secrete glucose-responsive C-peptide in patients with type 1 diabetes” has been published in the journal Cell Stem Cell.

Canadian researchers develop hand-held skin printer to treat burn patients

Researchers from the University of Toronto (UoT) Engineering and Sunnybrook Hospital, Canada, have developed a new 3D printer that can create sheets of skin to cover large burns and accelerate the healing process.

A simple schematic detailing the use (a) and general structure of the device (b).
Image credits Richard Y Cheng et al., (2020), Biofab.

Nobody likes to get burned — literally and figuratively. So a team of Canadian researchers has developed a handy new tool to take care of our literal burns. This hand-held 3D printer churns out stripes of biomaterial meant to cover burn wounds, promote healing, and reduce scarring. The bio-ink it uses is based on mesenchymal stromal cells (MSCs), a type of stem cell that differentiates into specialized roles depending on their environment.

Don’t feel the burn

“Previously, we proved that we could deposit cells onto a burn, but there wasn’t any proof that there were any wound-healing benefits — now we’ve demonstrated that,” says Axel Guenther, an Associate Professor of Mechanical Engineering at the UoT and the study’s corresponding author.

The team unveiled their first prototype of the printer in 2018. It was quite the novel gadget at the time, the first of its kind to form tissues on-site, deposit them, and have them set in place in under two minutes.

Since then, the team has redesigned the printer 10 times, in an effort to make it more user-friendly and to tailor it to the requirements of an operating room. The current iteration of the design includes a single-use microfluidic printhead (to ensure the part is always sterile), and a soft wheel that’s used to flatten the material and tailor it to wounds of different shapes and sizes.

The MSCs in the ink are intended to promote regeneration and reduce scarring, the team explains. In broad lines, the authors explain, the method is similar to skin grafting, but it doesn’t require for healthy skin to be transplanted from other areas of the patient’s body — it’s printed on the spot. This is especially useful in the case of large burns, they add.

“With big burns, you don’t have sufficient healthy skin available, which could lead to patient deaths,” says Dr. Marc Jeschke, director of the Ross Tilley Burn Centre and study co-author.

The team tested their printer in collaboration with the Ross Tilley Burn Centre and the Sunnybrook Hospital, successfully using the device to treat full-thickness wounds. Such burn wounds involve the destruction of both layers of the skin and often cover a significant portion of the body. While the results were encouraging, the team wants to further refine their printer and improve its ability to prevent scarring.

“Our main focus moving forward will be on the in-vivo side,” explains study leader Richard Cheng, a teaching assistant at the UoT.

“Once it’s used in an operating room, I think this printer will be a game changer in saving lives. With a device like this, it could change the entirety of how we practice burn and trauma care,” adds Jeschke.

The paper “Handheld instrument for wound-conformal delivery of skin precursor sheets improves healing in full-thickness burns” has been published in the journal Biofabrication.

Skin old, new.

Stem-cell-laden skin grafts could heal burn victims 30% faster, if not quicker

It’s the phoenix of skin grafts!

Skin old, new.

Image via Pixabay.

Researchers at the University of Toronto (UoT) are working to give burn victims their skin back. The team has developed a new process by which stem cells are retrieved from the burned skin and used to speed up recovery. Such a treatment option would greatly improve the chances of survival for those involved in fires or industrial accidents, as well as their quality of life to boot.

The team plans to start human trials by early 2019.

Skin to ashes, ashes to skin

“Because we’re using actual skin stem cells, and not from some other part of the body, we believe the quality of the skin will be better,” says Saeid Amini-Nik, a professor in the UoT Faculty of Medicine

“You want skin that stretches normally. In burn patients skin gets scarred and they have trouble moving joints because skin is not elastic.

Current procedures call for the removal and discarding of burned skin as medicinal waste. Collagen dressings are then applied to the site to protect the injury while it’s healing. This can take up to several months, however, during which patients are at high risk of developing (often fatal) infections.

Given the limitations of the current approach, researchers have long been interested in using stem cells to heal burns. Such cells were harvested from samples of organs from themselves or other patients/donors (such as umbilical cords, for example), which comes with its own host of problems:

  • Tissue incompatibility, leading to high rejection rates for the grafts.
  • Difficulties harvesting stem cells from the patients themselves. The cells used in such treatments are most often derived from undamaged portions of a patient’s skin or bone marrow. However, burn victims who need treatment with their own stem cells are usually those who have suffered extensive injuries — usually covering more than half of their bodies. Their extensive burns already pose a significant, potentially fatal risk, and they’re already at a high risk of infection. Surgically removing the skin or marrow needed for the treatment thus poses a real risk to their survival.

The team’s new approach started with them looking for live stem cells in samples of discarded dermis taken from burn victims. It was virtually unheard-of up to now, as it was considered a fool’s errand. The UoT researchers themselves hoped to find even one living cell in such samples — they were astonished to find thousands (even a million in one case) of living, usable cells in the burned tissue.

A preclinical trial involving animal models showed that adding human dermis stem cells to the collagen dressings improved healing speeds by 30%. There were no cases of rejection, and the stem cells naturally created skin to cover the wounds. The team hopes to see higher regrowth rates in the upcoming human trials, as they will be using human cells on people.

Cardiac stem cells.

Cardiac stem cells.
Image credits Gepstein Laboratory.

Amini-nik says the team expects the healing process to happen “very fast, possibly days instead of weeks or months,” which would be grand. Speed is key in healing burns, as each day spent with open wounds that need fresh dressings increases the chance of developing an infection — the baseline risk is already very high, and “sometimes [patients] die of sepsis.

Another major plus is that “using a patient’s own stem cells also won’t raise ethical issues,” the team explains.

“Much faster healing would be a major step forward,” says Amini-Nik. “We also believe this will be better for quality of life: Itching and inability to sweat are big problems for burn patients. We believe if we use the stem cells from the very same organ, we’ll grow better skin. ”

“Our goal is no death, no scar, and no pain,” adds Marc Jeschke, paper co-author. “With this approach we come closer to no death and no scar.”

The paper “Stem cells derived from burned skin – The future of burn care” has been published in the journal EBioMedicine.