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

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to evaluate the safety and tolerability of injecting certain cells produced in bone marrow called mesenchymal stromal cells (MSCs) into salivary glands. The main question it aims to answer is whether injection of MSCs into salivary glands results in any improvement in dry mouth. Participants will: * have bone marrow collected using a needle * undergo a salivary gland ultrasound * complete questionnaires * receive an injection of the bone marrow cells into a salivary gland

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.

What data supports the effectiveness of the treatment Mesenchymal Stromal Cells for Dry Mouth?

Research suggests that adipose-derived mesenchymal stem cells (a type of cell that can develop into different types of tissues) have shown potential in restoring salivary gland function in patients who have undergone radiation therapy for head and neck cancer, which often causes dry mouth. ^{1 2 3 4 5}

Are mesenchymal stromal cells safe for use in humans?

Research indicates that mesenchymal stromal cells (MSCs) are generally safe in humans, with transient fever being the most common treatment-related side effect. They have fewer safety concerns compared to embryonic stem cells. ^{1 6 7 8 9}

How is the treatment with Mesenchymal Stromal Cells for dry mouth different from other treatments?

Mesenchymal Stromal Cells (MSCs) are unique because they are adult stem cells capable of transforming into various cell types, which can help regenerate tissues. This regenerative ability makes them different from standard treatments, as they offer a novel approach to potentially repair and restore function in tissues affected by dry mouth. ^{1 10 11 12 13}

Research Team

Jacques Galipeau, MD

Principal Investigator

University of Wisconsin, Madison

Sara McCoy, MD, PhD

Principal Investigator

University of Wisconsin, Madison

Eligibility Criteria

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.

I am between 18 and 90 years old.

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Differential properties of human stromal cells from bone marrow, adipose, liver and cardiac tissues. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Intraglandular mesenchymal stem cell treatment induces changes in the salivary proteome of irradiated patients. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Enhancement of fat graft survival by bone marrow-derived mesenchymal stem cell therapy. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Systemic transplantation of human adipose tissue-derived mesenchymal stem cells for the regeneration of irradiation-induced salivary gland damage. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Studies in adipose-derived stromal cells: migration and participation in repair of cranial injury after systemic injection. [2021]

6. United Arab Emirates 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. [2023]

7. England pubmed.ncbi.nlm.nih.gov

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

8. United States pubmed.ncbi.nlm.nih.gov

Mesenchymal stromal cells: past, present, and future. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Emerging Role of Oral Mesenchymal Stem/Stromal Cells and Their Derivates. [2023]

10. Romania pubmed.ncbi.nlm.nih.gov

The role of dental stem cells in regeneration. [2020]

11. Spain pubmed.ncbi.nlm.nih.gov

Dental stem cells--characteristics and potential. [2022]

12. Iran pubmed.ncbi.nlm.nih.gov

Phenotypic characterizations and comparison of adult dental stem cells with adipose-derived stem cells. [2022]

13. Thailand pubmed.ncbi.nlm.nih.gov

Effects of demineralized bone matrix on proliferation and osteogenic differentiation of mesenchymal stem cells from human umbilical cord. [2018]