The ANOVA Xerostomia and Sjögren’s Syndrome
Stem Cell Secretome Treatment Programme Germany

You have tried a lot. Perhaps you have been told there is nothing more to be done. We listen first, examine thoroughly, and then tell you honestly whether a stem cell-based therapy, one of our programmes or another option could be right for you. Each option is discussed as an addition to your current treatment, never as a replacement.

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Dry mouth (xerostomia) is the feeling that the mouth is too dry, usually because the salivary glands produce too little saliva (hyposalivation). Saliva moistens food, protects the teeth and the lining of the mouth, and is needed for tasting, chewing, swallowing and speaking. Dry mouth affects about one in five adults, and more than four in five people who receive radiotherapy for head and neck cancer.^[2],[4]

The most common causes are medication, radiotherapy of the head and neck and Sjögren’s disease (Sjögren’s syndrome), an autoimmune disease of the salivary and tear glands.^[1] Radiation-induced xerostomia develops when the major salivary glands lie in the radiation field during treatment of cancer of the mouth, throat or larynx; it often persists long after treatment. The diagnosis rests on the medical history, an examination of the mouth and the measurement of saliva flow (sialometry), sometimes completed by ultrasound, scintigraphy or MRI of the glands. To date no cure is known for dry mouth caused by radiotherapy or by Sjögren’s disease.

Common symptoms include a sticky, dry feeling in the mouth, thirst, difficulty chewing, swallowing and speaking, a changed sense of taste, a burning tongue, bad breath, problems with dentures and dental decay.

More details can be found below in our scientific section on dry mouth (xerostomia).

Sjögren’s syndrome, now often called Sjögren’s disease, is a systemic autoimmune disease. Immune cells infiltrate the salivary and tear glands and damage the gland tissue, so that the mouth and the eyes become dry.^[32] It affects about 61 in 100,000 people, women about ten times as often as men.^[7] Besides the dryness, many people have fatigue and joint pain, and some develop involvement of other organs. The risk of non-Hodgkin lymphoma is several times higher than in the general population.^[32],[33]

The diagnosis follows the 2016 ACR/EULAR classification criteria, which combine antibodies against SSA/Ro, a lip biopsy and measurements of tear and saliva flow.^[12] Treatment relieves the dryness and treats any organ involvement; no cure is known.^[18] At ANOVA IRM, people with dry mouth caused by Sjögren’s syndrome are treated individually with MSEC, together with their rheumatologist: after an ultrasound of the salivary glands, MSEC is injected locally into the glands. More about other autoimmune diseases is on our autoimmune diseases page.

ANOVA offers autologous mesenchymal stem cell secretome (MSEC) therapy for people with lasting dry mouth, in addition to their dental care and the treatment their doctors prescribe. The programme combines a diagnostic MRI with repeated injections of MSEC into the salivary glands. Each component is selected individually; the programme is not a fixed package. Dry mouth belongs to our area of translational medicine — works in progress, in which each treatment is planned case by case.

Stem cells are thought to act mainly through soluble factors, together called the secretome, which includes exosomes and many other factors. After radiotherapy, the salivary glands lose saliva-producing cells, and inflammation, damage to small blood vessels and scarring can continue for months. MSEC is intended to potentially influence this environment and the function of the gland tissue that remains; it is not intended to replace glands that have been destroyed.

ANOVA IRM has not yet tested MSEC in a clinical study. The current state of research is described in the clinical and scientific section below.

An MRI of the head and neck, with contrast where needed, shows the size and structure of the salivary glands and the region of your former tumour. It helps to plan treatment with MSEC and does not replace the follow-up by your oncologist.

MSEC is the cell-free mixture of signalling molecules released by your own mesenchymal stromal cells from fat tissue, injected into the salivary glands. External laboratory and animal studies suggest that such factors may reduce radiation damage and scarring in salivary glands.^[27],[28] In Sjögren’s syndrome, external mouse studies suggest that vesicles from such cells may dampen the immune attack on the salivary glands.^[35],[36] Small external clinical studies with mesenchymal stem cells — cells, not secretome — are summarised in the clinical and scientific section below.

Dental care, fluoride and saliva substitutes are not part of our programme; they continue with your dentist and doctors at home.

Which tests are used to diagnose dry mouth (xerostomia)?

Dry mouth is diagnosed from the medical history, an examination of the mouth and the measurement of saliva flow at rest and after stimulation (sialometry). Imaging can show the condition of the glands: ultrasound and MRI with or without contrast show their structure, and scintigraphy shows their function. If Sjögren’s disease is suspected, blood tests for antibodies, a tear test and sometimes a small lip biopsy follow.

What do we review before xerostomia treatment at ANOVA IRM?

Before any treatment decision we review the reports on your tumour and its treatment, the end date of your radiotherapy, your latest follow-up results and any saliva measurements. We look at your current medication and dental status and check that you are fit for the brief sedation required for tissue collection.

• Standard: an MRI of the abdominal wall to exclude a hernia is required before the liposuction, taken no more than four weeks beforehand. It can be done at home or at ANOVA IRM.
• Optional: ultrasound guidance by ANOVA IRM for the injections into the salivary glands, used while the dose is given.
• In Sjögren’s syndrome: an ultrasound of the salivary glands by ANOVA IRM before the first injection.
• Optional: further MRI scans of the head and neck, with or without contrast, where your situation calls for them. Examples are documenting the condition of the salivary glands before treatment or clarifying a finding on an earlier scan.

Imaging can be carried out in-house; all examinations can also be done by your own doctors. The full diagnostic pathway is described on our diagnostics page.

ANOVA IRM has made MSEC in its own facility in Offenbach since 2018 (see our regulatory status). The injections into the salivary glands are planned with the radiology in the same building. Your oncologist, ENT specialist and dentist remain the basis of your care.

The first assessment can take place remotely, by phone or video, before any journey to Germany. Treatment itself takes place in person in Offenbach am Main, less than 20 minutes from Frankfurt Airport. Before you decide, you receive an individual written cost estimate; the services of our patient care team are free of charge. If you would like existing findings assessed independently, we also offer a second opinion.

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In this section you will find everything about treatment for dry mouth (xerostomia) at ANOVA IRM: who is eligible, the process step by step and the cost.

1. 01
   Initial evaluation

   Remote, by phone or video — typically 2 weeks to a few months

2. 02
   Preliminary screening

   In your home country, to avoid an unnecessary journey

3. 03
   First visit — bloodwork and tissue collection

   Two-day outpatient visit to Offenbach: bloodwork first, then — if the results are in order — mini-liposuction under brief sedation

4. 04
   Production and quality control

   Approximately 4 weeks; yields 10 doses per production cycle

5. 05
   Storage

   Up to 2 years, allowing an extended personalised schedule

6. 06
   Application schedule

   Set individually: one or two doses per application, depending on the number of salivary glands treated; every 4–6 weeks or at longer intervals, depending on how far away you live

We mainly consider adults with lasting dry mouth after radiotherapy for head and neck cancer. Your cancer treatment should have been completed at least two years ago, and your most recent follow-up should show no sign of the tumour returning. Your oncologist should confirm this in writing. The two-year interval matters because the secretome contains growth factors and is injected close to the former tumour region. Some saliva production should remain, because MSEC is intended to act on gland tissue that is still present. People with dry mouth from Sjögren’s syndrome are treated individually, together with their rheumatologist; an ultrasound of the salivary glands comes first. If medication is the likely cause, the first step is a review of that medication with your own doctor. You need to be well enough for mini-liposuction under light sedation and able to travel to Offenbach for repeated applications. Every treatment recommendation follows a full clinical evaluation in which the treating physician weighs benefit and risk. Applying for an evaluation does not mean that treatment will be offered.

What are the contraindications for xerostomia treatment?

Our treatments are experimental. We treat only people for whom, after medical assessment, we consider the benefit-risk balance to support treatment.

Applies to all ANOVA treatments:

• Active cancer within the last two years
• Under the age of legal majority
• Pregnancy or breastfeeding
• Active infectious disease (hepatitis A, B, C, HIV, syphilis or other)

Specific to dry mouth:

• Any sign of a tumour recurrence or a new tumour in the head and neck region
• Acute inflammation of a salivary gland (sialadenitis) or an infection of the skin or mouth at the injection site
• No remaining salivary gland tissue, for example after surgical removal of the glands
• Active osteoradionecrosis of the jaw (bone damage after radiotherapy)
• In Sjögren’s syndrome: a mass in a salivary gland on ultrasound, until it has been clarified

Blood-thinning medication is not a contraindication in itself. Whether it needs to be paused for the fat collection and the injections is decided with your treating doctors; please never stop it on your own.

Severely restricted mouth opening (trismus) after radiotherapy is not a contraindication in itself, but it requires an anaesthesia assessment beforehand, because it can make the airway more difficult to manage during sedation.

What screening is needed before you travel for xerostomia treatment?

A preliminary screening in your home country helps you avoid an unnecessary journey. It usually consists of a blood test for HIV, hepatitis A, B or C, syphilis and other active infections. Together with your oncology follow-up reports, it also shows early whether medical factors would rule out treatment.

What happens at your first visit to Offenbach for dry mouth?

The first treatment visit takes about two days in Offenbach and is outpatient. On the first day, bloodwork is repeated at ANOVA IRM as German medical rules require, and the physician completes the final assessment, including your mouth, salivary glands, jaw opening and airway for the sedation. If the results are in order, a small amount of abdominal fat tissue is collected the next day by mini-liposuction under brief sedation. The first secretome application usually follows four to six weeks later.

How is your MSEC for xerostomia produced and quality-controlled?

In our own facility in Offenbach, mesenchymal stromal cells are isolated from the collected fat tissue and expanded. This takes place under official authorisation and officially inspected good professional practice (GFP, gute fachliche Praxis; similar to Good Tissue Practice, GTP, in the US, but more than GTP). From these cells we obtain your MSEC — the signalling molecules they release, not the living cells. Production and quality control take approximately four weeks and yield 10 doses per production cycle. Every patient batch is tested with methods validated according to the European Pharmacopoeia (Ph. Eur.) and GMP and released under a documented procedure. The released secretome is stored at −80 °C and keeps for up to two years.

How often is MSEC applied for dry mouth?

Radiation-induced dry mouth is often a lasting condition, and there is currently no cure. We therefore recommend a longer-term treatment using all 10 doses produced rather than a single application; see the timeline above. How long the treatment lasts depends on how far away you live and on how many salivary glands are treated.

The schedule is set individually for each patient, for example:

• At every application: one or two doses of MSEC, depending on how many salivary glands are treated; for example two doses when the glands on both sides are injected.
• If you live close by: every 4 to 6 weeks.
• If you live further away: at longer intervals, for example every 3 months.
• Standard route for dry mouth: local injection into the submandibular glands below the jaw, under ultrasound guidance. The injection is given by an ANOVA IRM physician, usually a radiologist, under local anaesthesia or, if you wish, under sedation by our anaesthesiologist. This is intended to bring the secretome to the tissue in which saliva is produced. The parotid glands in front of the ears are injected only after an individual decision.
• Individual alternative: intravenous, only if you specifically wish it.

All doses must be used within the two-year shelf life of the stored MSEC; continuing after that requires a new tissue collection and production cycle. Injections into the salivary glands are short outpatient procedures performed with ultrasound guidance; typical side effects are temporary swelling, bruising or pain of the gland.

MSEC treatment costs approximately €20,000–€36,000, depending on the number of doses (three to ten), and requires a two-day visit for tissue collection, followed by further visits. It is billed according to the German Medical Fee Schedule (GOÄ). The base package — the mini-liposuction and the first three MSEC doses — costs approximately €20,000; each further dose costs approximately €2,250. Because we recommend using all 10 doses over a longer period for a lasting condition such as radiation-induced dry mouth, most treatment plans reach the upper end of this range.

A double liposuction can be recommended for a chronic condition: it yields 20 doses, which can be used over the current shelf life of two years from a single collection. The cost is correspondingly higher and is shown in your individual estimate.

Further examinations and your sedation preferences also affect the total, and you receive an individual written estimate before any treatment decision. Our blog post on treatment cost explains what drives the cost of stem cell treatment in general. Travel, accommodation and other personal expenses, including those of an accompanying person, are not included. MSEC treatment for dry mouth is generally self-funded; you can still ask your insurer about possible reimbursement. All prices are subject to change.

Why does the cost of xerostomia treatment vary with the application route?

All treatments at ANOVA IRM are billed according to the German Medical Fee Schedule (Gebührenordnung für Ärzte, GOÄ); within it, the cost varies mainly with the route of application. For dry mouth we mainly administer MSEC locally into the salivary glands, because in our assessment it is most likely to act there: the damaged gland tissue is where saliva is produced. We use intravenous administration only if you specifically wish it. The exact cost of your treatment plan is set out in your individual written cost estimate.

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Xerostomia is the subjective feeling of a dry mouth. Salivary gland hypofunction, or hyposalivation, is the objectively measured reduction of saliva. Hyposalivation means unstimulated whole saliva of 0.1 mL per minute or less, or stimulated saliva of 0.5 to 0.7 mL per minute or less. Normal values are about 0.3 to 0.4 and 1.5 to 2.0 mL per minute.^[1] The two do not always go together: many people who feel a dry mouth still have a measurable saliva flow.^[1]

Saliva is produced by three pairs of major glands — the parotid, submandibular and sublingual glands — and by many minor glands in the lining of the mouth. In radiation-induced xerostomia, the glands lie in the radiation field when tumours of the mouth, throat or larynx are treated. Saliva flow falls by 50 to 60% within the first week of radiotherapy, and more than 80% of patients report xerostomia during and after treatment.^[4] Chronic xerostomia affects 64 to 91% of patients, depending on the dose and on whether the glands could be spared.^[4] Doctors grade it with scales such as LENT-SOMA, RTOG/EORTC and CTCAE, and with questionnaires such as the Xerostomia Questionnaire (XQ) and the EORTC QLQ-H&N35.^[15],[10]

What causes xerostomia, and what are the risk factors?

Medication is the most common cause of hyposalivation, followed by radiotherapy of the head and neck and Sjögren’s disease.^[1] A systematic review identified 56 substances with a higher level of evidence for causing salivary gland dysfunction, mainly from the alimentary, cardiovascular, genitourinary, nervous and respiratory groups.^[6] In Sjögren’s disease (also called Sjögren’s syndrome), the immune system attacks the salivary and tear glands. What causes the dry mouth and what keeps it going after radiotherapy are two different questions; the next section deals with the second.

• Radiotherapy: severe xerostomia is usually avoided if at least one parotid gland receives a mean dose below about 20 Gy, or both glands below about 25 Gy.^[5] Chemotherapy given at the same time can add to the damage.
• Medication: for example antidepressants, antipsychotics, opioids, diuretics, some blood pressure medicines and drugs for an overactive bladder.^[1],[6]
• Autoimmune disease: Sjögren’s disease, which affects women about ten times as often as men.^[7]
• Age and multiple medications: dry mouth becomes more common with age, mostly because older people take more medicines.^[2],[1]
• Other factors: dehydration, mouth breathing, smoking, diabetes and some infections.

What drives the damage in radiation-induced xerostomia?

Radiation damages the glands in several steps. The saliva-producing acinar cells are lost, and the stem and progenitor cells in the ducts that would normally replace them are depleted.^[4] Small blood vessels in the gland are injured, and an inflammatory response develops.^[4] Scarring (fibrosis) of the gland tissue generally appears four to six months after irradiation.^[4] Whether function returns depends mainly on the dose the glands received: in a phase 3 trial, saliva from the spared parotid gland recovered over two years with parotid-sparing radiotherapy, but not with conventional radiotherapy.^[15]

This is where our programme aims — at inflammation, fibrosis and the environment of the remaining gland tissue, not at the cause of the dry mouth, and not at a cure.

What happens in the salivary glands in Sjögren’s syndrome?

In Sjögren’s syndrome the damage has a different cause. Immune cells react against the body’s own proteins, such as SSA/Ro and SSB/La, infiltrate the salivary and tear glands and destroy the gland epithelium, so that less saliva is produced.^[32] Because this autoimmune process continues, the treatment of Sjögren’s syndrome stays with the rheumatologist, and any treatment with MSEC is planned together with them.^[18]

For dry mouth caused by cancer treatment, the international guideline of ISOO, MASCC and ASCO and the German S3 guideline on supportive care in oncology describe prevention and treatment.^[13],[14] Prevention comes first: radiotherapy techniques that spare the glands, such as intensity-modulated radiotherapy (IMRT), should be used where possible.^[13] In the phase 3 trial PARSPORT, grade 2 or higher xerostomia after 24 months affected 29% of patients after parotid-sparing IMRT and 83% after conventional radiotherapy.^[15] During radiotherapy, bethanechol or acupuncture may be offered.^[13]

For existing dry mouth, the guideline recommends mucosal lubricants and saliva substitutes, together with sugar-free lozenges or chewing gum.^[13] After radiotherapy, oral pilocarpine, oral cevimeline (not available in the EU), acupuncture or transcutaneous electrostimulation may be offered.^[13] A Cochrane review found limited evidence for pilocarpine: 42 to 51% of patients responded, response can take up to 12 weeks, and side effects such as sweating are common.^[16] In a randomised trial, acupuncture led to fewer xerostomia complaints after one year than standard care, but it was not clearly better than sham acupuncture.^[17] Daily fluoride, regular dental care and treatment of fungal infections protect the teeth and the lining of the mouth. In Sjögren’s disease, the EULAR recommendations base the choice on the remaining gland function: stimulation with lozenges or gum, muscarinic agonists such as pilocarpine, or saliva substitutes when little function remains.^[18]

These treatments relieve symptoms and protect the mouth, but none of them restores lost gland tissue. Research into cell-based approaches is exploring this question; whether it is possible has not been shown. MSEC does not replace standard care.

How is xerostomia diagnosed, and what do we not do ourselves?

Xerostomia is diagnosed by your ENT specialist, oncologist, dentist or rheumatologist, not by us. Saliva flow is measured with sialometry, unstimulated and stimulated.^[1] The function of the glands can be shown with salivary gland scintigraphy, and their structure with ultrasound and MRI, including MR sialography of the ducts.^[11] If Sjögren’s disease is suspected, the 2016 ACR/EULAR classification criteria combine anti-SSA/Ro antibodies, a lip biopsy, the Schirmer test of tear flow, an eye staining score and the unstimulated saliva flow.^[12] Follow-up after cancer treatment, with examination and imaging of the head and neck, also remains with your treating specialists.

What we do ourselves is imaging: ultrasound of the salivary glands and ultrasound guidance for the injections, both carried out by ANOVA IRM, and MRI of the head and neck with or without contrast. The MRI is carried out at the Prof. Dr. Stehling Institut für Bildgebende Diagnostik GmbH in the same building, which also belongs to Dr. Stehling. We do not perform sialometry, scintigraphy, lip biopsies or tumour follow-up; please bring these findings from your doctors.

MSC secretome (MSEC)

ANOVA IRM has not yet tested MSEC in a clinical study. MSEC is a mesenchymal stromal cell secretome: the growth factors, cytokines (cell-to-cell messengers) and extracellular vesicles released by these cells, without the cells themselves. Mesenchymal stem cells and mesenchymal stromal cells are two names for the same cells (MSC); the International Society for Cell & Gene Therapy recommends “stromal” for cells grown in the laboratory.^[25],[26]

In an external animal study in mice, secretome from human adipose-derived MSC given after irradiation of the salivary glands improved saliva production and preserved gland structure, with more cell division and less cell death.^[27] In another external mouse study, exosomes from human adipose stem cells increased saliva flow after irradiation and reduced scarring of the glands.^[28] In an external rat study, human adipose-derived stem cells injected into the irradiated glands were followed by about one and a half times more saliva after 24 weeks than in untreated animals.^[29] An external systematic review of 13 animal studies with MSC found higher saliva flow after radiation damage, with large differences between the studies.^[30]

In humans, only mesenchymal stem cells — cells, not secretome — have been tested so far. In the small external phase 1/2 trial MESRIX, 30 people after radiotherapy for throat cancer received their own adipose-derived MSC or placebo, injected into the submandibular glands under ultrasound guidance. Unstimulated saliva rose by about a third after one month and by half after four months in the cell group, but not in the placebo group; no adverse events were reported.^[19] In the small external phase 1 study MESRIX-II, ten patients received donor MSC into the parotid and submandibular glands; saliva flow and complaints improved after four months, without a control group.^[20] A small external pilot study with the patients’ own bone marrow MSC in six people found no serious adverse events.^[21] In Sjögren’s disease, a small external uncontrolled clinical study gave donor umbilical cord MSC into a vein to 24 patients and reported more saliva in those with dry mouth.^[23]

In the small external phase 2 trial MESRIX-III with 120 patients, donor MSC were compared with placebo. Saliva flow rose in both groups; a benefit of the cells over placebo could not yet be demonstrated after four months.^[22] An external meta-analysis of five randomised trials found, for radiation-induced xerostomia, a small increase in saliva flow and no treatment-related serious adverse events.^[24] To our knowledge, no clinical study has yet tested an MSC secretome or MSC-derived vesicles in dry mouth.

In Sjögren’s syndrome, an external systematic review of studies in patients and mice reported more saliva and less infiltration of the salivary glands by immune cells after mesenchymal stem cells given into a vein or the abdominal cavity, together with fewer inflammatory messengers; how they work is not yet known.^[34] In external mouse studies, extracellular vesicles from MSC reduced the infiltration of the salivary glands and the autoantibody levels, and MSC-derived exosomes suppressed a type of helper T cell that drives the disease.^[35],[36] In a small external randomised trial in Sjögren’s syndrome, donor MSC injected into the tear gland were compared with an injection of the carrier solution alone; dry eye complaints improved in both groups.^[37] To our knowledge, no clinical study has yet tested an MSC secretome in the salivary glands in Sjögren’s syndrome.

What is the efficacy hypothesis behind MSC secretome in xerostomia?

After radiotherapy, the salivary glands lose acinar cells and progenitor cells, and inflammation, damage to small vessels and fibrosis follow over months.^[4] The hypothesis is that the soluble factors of the mesenchymal stromal cell secretome, injected into the glands, influence this environment. In animal models they may dampen inflammation, protect gland cells from dying and reduce fibrosis, and with that support the function of the tissue that remains.^[27],[28] In Sjögren’s syndrome, the hypothesis is additionally that these factors dampen the immune attack on the glands.^[34],[35]

One limitation belongs with it: gland tissue that has been completely destroyed is not expected to be replaced. Our aim is to influence the function of the remaining gland tissue, not to cure dry mouth.

Talk to us about current changes or additions to the programme. For a number of conditions ANOVA IRM also offers infusion therapies alongside the components described above.

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We do not currently publish our own outcome data for dry mouth. What we can say about MSEC in xerostomia therefore rests on the published literature and on the rationale described above.

Stem cell-based therapy for dry mouth remains experimental, and outcomes vary from patient to patient. Treatment goals are agreed individually and followed with questionnaires on dryness, eating and speaking; saliva measurements can be carried out by your own doctors. Treatment cannot guarantee more saliva or fewer complaints.

What is the realistic goal of xerostomia treatment?

Care for dry mouth after radiotherapy aims to relieve the symptoms and to protect the teeth and the lining of the mouth.^[13] For MSEC, too, the aim is to support the function of the remaining gland tissue, not to rebuild glands that have been destroyed.

MSEC is an autologous tissue preparation made from the patient’s own fat tissue. ANOVA IRM manufactures it under a collection (procurement) authorisation (Section 20b AMG) and a manufacturing authorisation under Section 20c AMG. Both were granted by the competent authority of the State of Hesse, today the Hessian State Office for Health and Care (HLfGP), with the involvement of the Paul-Ehrlich-Institut; the HLfGP inspects the facility regularly. For dry mouth, MSEC is given as an individual therapeutic attempt (individueller Heilversuch), which concerns the administration only and follows full disclosure and informed consent. Because the product is used only for ANOVA IRM’s own patients, no authorisation under Section 4b, no marketing authorisation under Section 21 and no approval under Section 21a AMG is required. The full derivation is on our regulatory status page.

Questions people usually ask next. Each is answered in full on its own page.

• Who are we?
• Is ANOVA legal?
• Is stem cell therapy safe?
• What is MSC secretome (MSEC)?
• What is BMC (Bone Marrow Concentrate)?
• What are stem cells?
• What should I ask when looking for a stem cell treatment?
• Which conditions do we treat?
• Translational medicine — works in progress
• Autoimmune diseases — overview

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ANOVA IRM shares its premises in Offenbach with two further institutions owned by Dr. Stehling: the Institut für Bildgebende Diagnostik (IBDO), providing MRI and CT imaging, and the VITUS PRIVATKLINIK Prof. Dr. Stehling GmbH. Because imaging is carried out in the same building, condition-specific diagnostics — including MRI of the head and neck before treatment for dry mouth — can be performed in-house rather than referred elsewhere. See diagnostics at ANOVA IRM.

Literature specific to dry mouth (xerostomia) is listed here. General literature on MSC, secretome and extracellular vesicles is maintained on the MSC secretome page, bone marrow literature on the BMC page.

Dry mouth — definition, frequency, causes and course

• [1] Villa A, Connell CL, Abati S. Diagnosis and management of xerostomia and hyposalivation. Ther Clin Risk Manag. 2015;11:45–51. doi:10.2147/TCRM.S76282. PMID: 25653532.
• [2] Agostini BA, Cericato GO, Silveira ER, et al. How common is dry mouth? Systematic review and meta-regression analysis of prevalence estimates. Braz Dent J. 2018;29(6):606–618. doi:10.1590/0103-6440201802302. PMID: 30517485.
• [3] International Agency for Research on Cancer. Global Cancer Observatory: Cancer Today. GLOBOCAN 2024 (version 1.0), cancer fact sheets: lip and oral cavity, salivary glands, oropharynx, nasopharynx, hypopharynx, larynx. Lyon: IARC/WHO; 2026. Accessed 21 October 2026. https://gco.iarc.who.int/media/globocan/factsheets/cancers/1-lip-oral-cavity-fact-sheet.pdf
• [4] Jasmer KJ, Gilman KE, Muñoz Forti K, et al. Radiation-induced salivary gland dysfunction: mechanisms, therapeutics and future directions. J Clin Med. 2020;9(12):4095. doi:10.3390/jcm9124095. PMID: 33353023.
• [5] Deasy JO, Moiseenko V, Marks L, et al. Radiotherapy dose-volume effects on salivary gland function. Int J Radiat Oncol Biol Phys. 2010;76(3 Suppl):S58–S63. doi:10.1016/j.ijrobp.2009.06.090. PMID: 20171519.
• [6] Wolff A, Joshi RK, Ekström J, et al. A guide to medications inducing salivary gland dysfunction, xerostomia, and subjective sialorrhea: a systematic review sponsored by the World Workshop on Oral Medicine VI. Drugs R D. 2017;17(1):1–28. doi:10.1007/s40268-016-0153-9. PMID: 27853957.
• [7] Qin B, Wang J, Yang Z, et al. Epidemiology of primary Sjögren’s syndrome: a systematic review and meta-analysis. Ann Rheum Dis. 2015;74(11):1983–1989. doi:10.1136/annrheumdis-2014-205375. PMID: 24938285.
• [8] Schweyen R, Hey J, Fränzel W, et al. Radiation-related caries: etiology and possible preventive strategies. What should the radiotherapist know? Strahlenther Onkol. 2012;188(1):21–28. doi:10.1007/s00066-011-0011-1. PMID: 22189435.
• [9] Jensen SB, Vissink A, Limesand KH, Reyland ME. Salivary gland hypofunction and xerostomia in head and neck radiation patients. J Natl Cancer Inst Monogr. 2019;2019(53):lgz016. doi:10.1093/jncimonographs/lgz016. PMID: 31425600.

Diagnostics and standard of care

• [10] Memtsa PT, Tolia M, Tzitzikas I, et al. Assessment of xerostomia and its impact on quality of life in head and neck cancer patients undergoing radiation therapy. Mol Clin Oncol. 2017;6(5):789–793. doi:10.3892/mco.2017.1200. PMID: 28529753.
• [11] Wu VWC, Leung KY. A review on the assessment of radiation induced salivary gland damage after radiotherapy. Front Oncol. 2019;9:1090. doi:10.3389/fonc.2019.01090. PMID: 31750235.
• [12] Shiboski CH, Shiboski SC, Seror R, et al. 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren’s syndrome: a consensus and data-driven methodology involving three international patient cohorts. Arthritis Rheumatol. 2017;69(1):35–45. doi:10.1002/art.39859. PMID: 27785888.
• [13] Mercadante V, Jensen SB, Smith DK, et al. Salivary gland hypofunction and/or xerostomia induced by nonsurgical cancer therapies: ISOO/MASCC/ASCO guideline. J Clin Oncol. 2021;39(25):2825–2843. doi:10.1200/JCO.21.01208. PMID: 34283635.
• [14] Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF). S3-Leitlinie Supportive Therapie bei onkologischen PatientInnen, Langversion 2.1, 2026, Kapitel 11.10 Radiogene Xerostomie. AWMF-Registernummer 032-054OL. https://www.leitlinienprogramm-onkologie.de/leitlinien/supportive-therapie/
• [15] Nutting CM, Morden JP, Harrington KJ, et al. Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial. Lancet Oncol. 2011;12(2):127–136. doi:10.1016/S1470-2045(10)70290-4. PMID: 21236730.
• [16] Davies AN, Thompson J. Parasympathomimetic drugs for the treatment of salivary gland dysfunction due to radiotherapy. Cochrane Database Syst Rev. 2015;(10):CD003782. doi:10.1002/14651858.CD003782.pub3. PMID: 26436597.
• [17] Garcia MK, Meng Z, Rosenthal DI, et al. Effect of true and sham acupuncture on radiation-induced xerostomia among patients with head and neck cancer: a randomized clinical trial. JAMA Netw Open. 2019;2(12):e1916910. doi:10.1001/jamanetworkopen.2019.16910. PMID: 31808921.
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Mesenchymal stem cells in xerostomia — clinical studies (cells, other products than MSEC)

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Mesenchymal stromal cell secretome, extracellular vesicles and animal studies

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Approval status

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Sjögren’s syndrome — disease, mesenchymal stem cells and vesicles

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• [36] Rui K, Shen Z, Peng N, et al. Olfactory ecto-mesenchymal stem cell-derived exosomes ameliorate murine Sjögren’s syndrome via suppressing Tfh cell response. Rheumatol Immunol Res. 2022;3(4):198–207. doi:10.2478/rir-2022-0035. PMID: 36879843. PMCID: PMC9984929.
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