Mesenchymal Stromal Cells for Dry Mouth

Overseen By Cancer Connect

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Wisconsin, Madison

Must not be taking: Diuretics, Investigational drugs

Disqualifiers: Diabetes, Malignancy, Transfusion dependency, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 day

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether injecting mesenchymal stromal cells (MSCs) from bone marrow into the salivary glands can alleviate dry mouth. The primary goal is to determine the treatment's safety and its effectiveness in improving dry mouth symptoms. Individuals with non-radiation-induced dry mouth and very low saliva flow might be suitable candidates. Participants will undergo bone marrow collection, receive an injection into their salivary glands, and complete several tests. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Do I need to stop my current medications for this trial?

The trial does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy, you must be on a stable dose for at least 2 months.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

A previous study found that mesenchymal stromal cells (MSCs) showed promise in alleviating radiation-induced dry mouth. Researchers carefully monitored the study to ensure safety. Results indicated that MSCs were generally well-tolerated, with most participants experiencing no serious side effects. Some reported mild reactions, such as temporary swelling or discomfort at the injection site.

Another study investigated the direct injection of MSCs into salivary glands. This study also confirmed the safety of MSCs for participants, with no major safety concerns and only mild, temporary side effects.

As this trial is in its early stages, it primarily focuses on assessing the safety of injecting MSCs into salivary glands. Early-stage trials typically involve small groups and aim to identify potential safety issues. So far, evidence suggests that MSCs are safe and well-tolerated in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for dry mouth?

Most treatments for dry mouth focus on symptom management, using options like saliva substitutes, oral rinses, and medications to stimulate saliva production. Unlike these standard treatments, Mesenchymal Stromal Cells (MSCs) offer a novel approach by potentially addressing the root cause of dry mouth. MSCs are unique because they have regenerative properties, which might help repair and rejuvenate the salivary glands themselves, rather than just providing temporary relief. Researchers are excited about MSCs because they could lead to a more lasting solution for dry mouth, improving quality of life for those affected by this condition.

What evidence suggests that mesenchymal stromal cells might be an effective treatment for dry mouth?

Research has shown that certain cells, called mesenchymal stromal cells (MSCs), might help treat dry mouth. In this trial, participants will receive MSCs injected into their submandibular glands. Studies have found that injecting these cells directly into the glands can increase saliva production. One study showed that MSC treatment led to significant changes in saliva proteins, improving gland health over time. People who received MSC therapy reported fewer dry mouth symptoms. These findings suggest that MSCs could ease life for those dealing with dry mouth. ^{4 6 7 8 9}

Who Is on the Research Team?

Sara McCoy, MD, PhD

Principal Investigator

University of Wisconsin, Madison

Jacques Galipeau, MD

Principal Investigator

University of Wisconsin, Madison

Are You a Good Fit for This Trial?

This trial is for individuals with dry mouth due to conditions like Graft-versus-Host Disease or Sjögren's Syndrome. Participants will have bone marrow collected, undergo an ultrasound of their salivary glands, fill out questionnaires, and receive an injection of their own bone marrow cells into a salivary gland.

Inclusion Criteria

Willing and able to give informed consent

I am willing to use birth control during the study.

Radiographically confirmed bilateral submandibular glands

Exclusion Criteria

Life expectancy ≤ 6 months as determined by the investigator

My diabetes is not well-managed (HBA1c is 7% or higher).

I have been diagnosed with cancer in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline

Participants undergo bone marrow aspiration and salivary gland ultrasound

1 week

1 visit (in-person)

Treatment

Participants receive MSC injections into one or both submandibular glands

1 day

1 visit (in-person)

Dose Escalation

Dose escalation cohort receives MSC injections at increasing doses

Varies

Expansion

Expansion cohort receives MSC injections at the recommended phase II dose

Varies

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Multiple visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Mesenchymal Stromal Cells

Trial Overview The trial is testing the safety and potential benefits of injecting mesenchymal stromal cells (MSCs) at two different dose levels directly into the salivary glands to see if it can improve symptoms of dry mouth in patients.

How Is the Trial Designed?

Group I: MSCs Dose Level 0 into one submandibular gland Active Control 1 Intervention

6 subjects will receive Mesenchymal Stromal Cells (MSC) at Dose Level 0, which is 10 (8-12) x10\^6 MSCs in a single submandibular gland. If this dose is deemed tolerable when injected into a single submandibular gland, this dose will be administered to both submandibular glands in the initial subjects in the dose escalation arm.

Group II: MSCs into both submandibular glands - Dose Escalation Cohort Active Control 2 Interventions

8-18 subjects in the Dose Escalation phase of study will receive MSCs into both submandibular glands. The initial subjects in this cohort will receive Dose Level 0: 10 (8-12) x10\^6 MSCs/gland. If this dose is tolerated, subsequent subjects will receive Dose Level 1: 20 (16-24) x10\^6 MSCs/gland. The highest tolerated dose (recommended phase II dose or RP2D) will be administered to the subjects in the Expansion Cohort.

Group III: MSCs into both submandibular glands - Expansion Cohort Active Control 2 Interventions

12 subjects in Expansion Cohort will receive MSCs into both submandibular glands at the RP2D.

Mesenchymal Stromal Cells is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Mesenchymal Stromal Cells for:

• Graft-versus-host disease (GVHD)
• Autoimmune diseases

Approved in United States as Mesenchymal Stromal Cells for:

• Graft-versus-host disease (GVHD)
• Pediatric steroid-refractory GVHD

Approved in Canada as Mesenchymal Stromal Cells for:

• Pediatric steroid-refractory GVHD

Approved in Japan as Mesenchymal Stromal Cells for:

• Pediatric steroid-refractory GVHD

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

Published Research Related to This Trial

Dental tissues are a rich source of mesenchymal stem cells (MSCs), which have the ability to differentiate into various cell types and play a crucial role in tissue regeneration.

The properties of dental-derived MSCs, such as their high proliferation rate and positive expression of mesenchymal cell markers, make them promising candidates for future regenerative medicine applications, particularly in repairing craniofacial structures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of dental stem cells in regeneration. Maxim, MA., Soritau, O., Baciut, M., et al.[2020]

Mesenchymal stromal cells (MSCs) from different tissues, including bone marrow, heart, adipose, and liver, share similar morphology and phenotype, but their functional properties differ significantly, particularly in their interaction with tumor cells.

Heart stromal cells (HS) uniquely inhibit the proliferation of tumor cells, which may explain the lower incidence of tumors in cardiac tissue, while bone marrow and adipose-derived MSCs may support tumor growth, suggesting careful consideration is needed when using these cells in therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential properties of human stromal cells from bone marrow, adipose, liver and cardiac tissues. Kellner, J., Sivajothi, S., McNiece, I.[2018]

Adult mesenchymal stromal cells are unique because they can self-renew and turn into different types of tissues, making them valuable for tissue engineering and regenerative medicine.

Recent studies show promising results for the clinical use of these cells, highlighting their potential in treating various conditions due to their immune privilege.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesenchymal stromal cells: past, present, and future. Spencer, ND., Gimble, JM., Lopez, MJ.[2022]

Mesenchymal stem/stromal cells (MSCs) present fewer ethical and moral concerns compared to embryonic stem cells, making them a more acceptable option for research and therapy.

MSCs also have a better safety profile, which is crucial for their potential use in regenerative medicine and other therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging Role of Oral Mesenchymal Stem/Stromal Cells and Their Derivates. Marconi, GD., Diomede, F., Pizzicannella, J., et al.[2023]

In a study involving 8 head and neck cancer patients with radiation-induced dry mouth, treatment with adipose tissue-derived mesenchymal stem/stromal cells (AT-MSCs) significantly altered the salivary proteome, with 99 proteins showing differential expression after 120 days.

While AT-MSC treatment increased proteins associated with tissue regeneration, it did not fully restore the salivary profile to that of healthy controls, indicating that while the treatment has potential, it may not completely reverse the effects of radiation-induced damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraglandular mesenchymal stem cell treatment induces changes in the salivary proteome of irradiated patients. Lynggaard, CD., Jersie-Christensen, R., Juhl, M., et al.[2022]

Systemic administration of human adipose-derived mesenchymal stem cells (hAdMSCs) significantly improved salivary flow rates and reduced cell damage in irradiated salivary glands of mice, indicating their potential efficacy in repairing radiation-induced damage.

hAdMSCs not only protected against cell loss but also demonstrated the ability to differentiate into salivary gland epithelial cells, suggesting a mechanism of action that could enhance recovery of gland function after radiation exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic transplantation of human adipose tissue-derived mesenchymal stem cells for the regeneration of irradiation-induced salivary gland damage. Lim, JY., Ra, JC., Shin, IS., et al.[2021]

Umbilical cord mesenchymal stem (UCMS) cells can differentiate into bone-forming cells when treated with demineralized bone matrix (DBM), indicating their potential for use in tissue engineering and regenerative medicine.

DBM treatment inhibited UCMS cell growth by 50% but significantly enhanced their osteogenic differentiation, as shown by increased alkaline phosphatase activity, which is an early marker of bone cell development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of demineralized bone matrix on proliferation and osteogenic differentiation of mesenchymal stem cells from human umbilical cord. Honsawek, S., Dhitiseith, D., Phupong, V.[2018]

Mesenchymal stem cells (MSCs) can be successfully isolated and cultured from both human adipose tissue and dental pulp of exfoliated deciduous teeth, showing promise for treating and preventing diseases like type 1 diabetes and liver fibrosis.

Both cell populations expressed key stem cell markers (CD44, CD90, CD13) but differed in the expression of other markers, indicating that dental pulp-derived MSCs may have unique properties that could be beneficial for therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phenotypic characterizations and comparison of adult dental stem cells with adipose-derived stem cells. Alipour, R., Sadeghi, F., Hashemi-Beni, B., et al.[2022]

A meta-analysis of 152 randomized clinical trials involving 9228 individuals treated with mesenchymal stromal cells (MSCs) found that fever is the only adverse event closely associated with MSC therapy, with a significant odds ratio of 1.61.

The analysis also indicated that MSC therapy may lower the incidence of tachycardia and fatigue, although these findings were not statistically significant, suggesting a generally favorable safety profile for MSC treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transient Fever: the Sole Treatment-Related Adverse Event associated with Mesenchymal Stromal Cells and Solid Clues from the Real World. Wang, Y., Mou, Q., Yi, H., et al.[2023]

Mesenchymal Stem/Stromal Cells (MSCs) have the potential to differentiate into key cell types like chondrocytes, osteoblasts, and adipocytes, but their existence and role in vivo remain debated due to challenges in proving their lineage.

The article suggests that MSCs likely originate from the lateral plate mesoderm, providing an embryological basis for their existence, and emphasizes the need for better integration of MSC research with developmental biology to advance understanding and applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The developmental basis of mesenchymal stem/stromal cells (MSCs). Sheng, G.[2023]

Dental stem cells, derived from soft dental tissues, are multipotent mesenchymal stem cells that can differentiate into various cell types, including those needed for bone, fat, and nerve tissue, making them valuable for regenerative medicine.

There are five types of dental stem cells identified, which can be utilized in dental tissue engineering and may also hold potential for treating neurodegenerative and immune diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dental stem cells--characteristics and potential. Bojic, S., Volarevic, V., Ljujic, B., et al.[2022]

Bone marrow-derived mesenchymal stem cells significantly enhance fat graft survival compared to a control group, with the highest survival rates observed in grafts treated with these cells.

Expanded bone marrow-derived mesenchymal stem cells also improve fat graft survival, but to a lesser extent than non-expanded cells, indicating that the potency of the stem cells plays a crucial role in the effectiveness of fat grafting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancement of fat graft survival by bone marrow-derived mesenchymal stem cell therapy. Zhao, J., Yi, C., Zheng, Y., et al.[2021]

Intravenously administered adipose-derived stromal cells successfully migrated to and accumulated at surgically created cranial defects in mice, indicating their potential for targeted healing.

Human adipose-derived stromal cells, in particular, demonstrated significant bone formation at the defect sites, suggesting they could be an effective treatment for skeletal regeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Studies in adipose-derived stromal cells: migration and participation in repair of cranial injury after systemic injection. Levi, B., James, AW., Nelson, ER., et al.[2021]

Citations

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Intraglandular mesenchymal stem cell treatment induces ... AT-MSC treatment induce a significant impact on the salivary proteome, as 99 proteins are differentially expressed at baseline vs. 120 days after treatment.

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Primary Results of the MESRIX Phase I/II Randomized Trial Mesenchymal stem/stromal cell therapy may reduce radiation-induced xerostomia. We investigated the long-term safety of autologous adipose tissue-derived ...

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Study Transplanting Bone Marrow Cells Into Salivary ... The goal of this clinical research study is to evaluate the safety and tolerability of injecting certain cells that you produce in your bone marrow called ...

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Long-term Effectiveness and Safety of Mesenchymal Stromal ... The salivary glands are especially susceptible to radiation, which induces both acute and chronic salivary gland damage, including inflammation, fibrosis, and ...