Photo: Kathrine Kronberg Jakobsen, a physician and PhD student, is part of the team working on stem cells for cancer patients.
Mouth dryness is one the most serious nuisances of all for cancer patients who have received radiotherapy in their throat region. The treatment damages their salivary glands, and without the protective saliva, there is a serious risk of dental problems, and patients may have to live with a mouth too dry to eat a normal meal. However, promising research results from Copenhagen University Hospital - Rigshospitalet now give hope that stem cell treatment can improve saliva amounts and the quality of life for these patients. This is according to Professor Christian von Buchwald from the Department of Otorhinolaryngology, Head and Neck Surgery & Audiology at Copenhagen University Hospital - Rigshospitalet. He has been at the forefront of research into the saliva function and stem cells for more than a decade.
“Despite massive research into improving saliva production for 20 years, there’s been no major breakthrough for patients within our area. But for the first time, we can now demonstrate that stem cells can improve patients' saliva function. We’ve also established new knowledge about the mechanism of action of stem cells. We consider this as something of a breakthrough, and there are huge perspectives,” said Christian von Buchwald.
The results have been published in the scientific journal STEM CELLS Translational Medicine, with the Physician Charlotte Duch Lynggaard as the first author. She has demonstrated in her PhD project that treatment with donor stem cells (allogeneic cells) is relevant and can be used routinely in clinics. Charlotte Duch Lynggaard and her colleagues from the University of Copenhagen and Roskilde University are the first in the world to find that the treatment also significantly changes the composition of the salivary proteome. This takes place when the treatment helps upregulate proteins to promote cell regeneration.
Life on blended food
Photo: Professor Christian von Buchwald’s research groups have spent more than two decades searching for a treatment to help cancer patients with mouth dryness after radiotherapy has damaged their salivary glands.
The treatment could potentially help the increasing number of patients with cancer in the throat region. Research from Christian von Buchwald’s group has shown that human papilloma virus (HPV), in particular, is why more otherwise healthy people are getting cancer in the throat and tonsils, for example. They also have problems with saliva production when they receive radiotherapy in and around the salivary glands.
“The diseases strike people who should have many years left on the labour market, and have to live with the consequences of poor saliva production for a great many years. Quality of life is severely impaired if you have to live on blended food,” said Christian von Buchwald.
There are even greater perspectives in the longer term, because patients in immuno- and chemotherapy also risk damage to their salivary glands.
The latest research is based on the so-called allogeneic cells, which are produced under the management of Professor Jens Kastrup in the Cardiac Stem Cell Lab at Copenhagen University Hospital - Rigshospitalet. Here, they harvest stem cells from healthy people and propagate them for use in treatment within different disease areas.
As part of Consultant Christian Grønhøj’s PhD project, Christian von Buchwald’s research team have previously worked with autologous cells, and they have harvested stem cells from the stomach fat in patients themselves so patients’ own stem cells are injected into their salivary gland. The research demonstrated a 50% improvement in saliva production, but the process of harvesting the stem cells was time-consuming and difficult for patients.
The bank of the stem cells from the Cardiac Stem Cell Lab makes it more realistic for stem cells to be used at large scale in the department.
But first treatment has to be tested and compared with a control group. Currently, Physician and PhD student Kathrine Kronberg Jakobsen is completing a randomised trial in which either allogeneic cells or a placebo-liquid is injected into the salivary glands of patients with head and neck cancer. The trial subjects are tested for how much saliva they can produce before and after treatment.
"We injected about 25 million stem cells into the large submandibular glands. We hope that this approach will provide good results, although it is too early to conclude,” said Kathrine Kronberg Jakobsen.
She says that, from the studies by Christian Grønhøj and Charlotte Lynggaard, we can see that the effect of the treatment typically takes place gradually over a number of months and even years, indicating that the treatment will work for a long time.
“Of course we very much hope that our trials will show that the treatment works for most people,” said Kathrine Kronberg Jakobsen.
The researchers have so far only found minimal side effects in the form of minor, temporary pain and swelling. The initial results of the clinical trial are expected to be ready during 2023.
The journey of saliva research towards stem cells
- In 2005, Professor Christian von Buchwald and researchers from the University of Copenhagen were behind a patent on sour candy that could stimulate saliva production, without the acid destroying teeth. However, the effect on patients depended on whether there was relatively large saliva production already.
- Instead, Christian von Buchwald and his colleagues began to look at the most promising perspectives in stem cells, which could help to regenerate the function of salivary glands.
- In 2014, Physician Christian Grønhøj started on a PhD project in which researchers produced stem cells from patients’ own fat cells in the stomach, then propagated them and injected them into patients’ salivary glands (autologous cells). On average this gave a 50 per cent higher saliva production after four months for a group of people with mouth dryness following treatment for head and neck cancer. However, the process was difficult for patients, and it took a lot of time.
- Ear-nose-throat researchers then looked to the Cardiac Stem Cell Lab at Copenhagen University Hospital - Rigshospitalet, where Professor Jens Kastrup had successfully produced stem cells harvested from healthy people. These allogeneic cells made it was possible to inject 4-5 times as many stem cells into patients’ salivary glands, and the process was easier.
- In a PhD project, which began in 2019, Physician Charlotte Lynggaard demonstrated that treatment with donor stem cells (allogeneic cells) was possible.
- Physician Amanda-Louise Fenger Carlander also plans to examine retreatment with stem cells.
- In a new large PhD project, with 120 patients, Physician Kathrine Kronberg Jakobsen is conducting a blind randomized controlled trial in which patients with head and neck cancers and very low saliva production either have allogeneic cells or saline solution injected into their salivary glands.