Mesenchymal Stem Cell + Islet Transplant for Chronic Pancreatitis

Overseen By Leah Benn, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Medical University of South Carolina

Must not be taking: Immunosuppressants

Disqualifiers: Pregnancy, Breastfeeding, Liver damage, others

Compensation: Varies

Number of Visits: 4

Duration: 1 day

42 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a clinical trial for chronic pancreatitis (CP) patients undergoing total pancreatectomy with islet autotransplantation (TP-IAT). Participants will be randomized to either bone marrow-derived mesenchymal stem cells (MSCs) or control with the standard of care. Participants will be followed for one-year post-transplant.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on immunosuppressive drugs, you may not be eligible to participate.

What data supports the effectiveness of this treatment for chronic pancreatitis?

Research shows that bone marrow-derived mesenchymal stem cells (MSCs) can reduce inflammation and improve outcomes in conditions like acute pancreatitis and islet transplantation in animal models. This suggests potential benefits for chronic pancreatitis by reducing inflammation and supporting cell function. ^{1 2 3 4 5}

Is the combination of mesenchymal stem cells and islet transplantation safe for humans?

A study on patients with chronic pancreatitis who received mesenchymal stem cells (MSCs) and islet cotransplantation showed no adverse events directly related to the MSC infusions, suggesting it may be safe for humans. ^{1 4 5 6 7}

How does the Mesenchymal Stem Cell + Islet Transplant treatment for chronic pancreatitis differ from other treatments?

This treatment is unique because it combines mesenchymal stem cells (MSCs) with islet transplantation, which may improve the survival and function of transplanted islets by reducing inflammation and enhancing engraftment. Unlike standard treatments, this approach potentially offers better glycemic control and quality of life for patients with chronic pancreatitis. ^{1 2 4 6 8}

Research Team

Charlton Strange, M.D

Principal Investigator

Medical University of South Carolina

William Lancaster, M.D

Principal Investigator

Medical University of South Carolina

Hongjun N Wang, PhD

Principal Investigator

Medical University of South Carolina

Eligibility Criteria

This trial is for adults over 18 with chronic pancreatitis, scheduled for a specific surgery (TP-IAT), and have not had major pancreatic surgeries or diabetes before the surgery. It's not for those with significant liver damage, prior certain pancreatic surgeries that affect islet yield, or women who are pregnant/breastfeeding. People under immunosuppression are also excluded.

Inclusion Criteria

I am 18 years old or older.

I have chronic pancreatitis and am scheduled for a total pancreatectomy with islet autotransplantation.

My diabetes is under control with an HbA1c level below 12%.

Exclusion Criteria

Patients who are under immunosuppression

Pregnant and breastfeeding women

My liver tests show damage more than three times the normal levels.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo total pancreatectomy with islet autotransplantation and receive either islet transplantation alone or islets plus autologous bone marrow-MSCs at two different doses

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety, islet function, glycemic control, pain relief, quality of life, and adverse events

12 months

3 visits (in-person) on days 90, 180, and 365

Treatment Details

Interventions

• Bone marrow-derived mesenchymal stem cells
• Placebo

Trial Overview The study tests if bone marrow-derived mesenchymal stem cells can help patients recovering from TP-IAT surgery compared to the standard care without these cells. Participants will be randomly assigned to receive either the stem cells or a placebo and monitored for one year.

Participant Groups

Group I: BM-MSCs at 50x10^6 Experimental Treatment 1 Intervention

One time infusion of islets plus BM-MSCs at 50x10\^6/patient, n=14

Group II: BM-MSCs at 20x10^6 Experimental Treatment 1 Intervention

One time infusion of islets plus BM-MSCs at 20x10\^6/patient, n=14

Group III: Placebo Placebo Group 1 Intervention

One time infusion of islets only.

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Findings from Research

Human bone marrow-derived clonal mesenchymal stem cells (hcMSCs) showed significant potential in reducing inflammation and tissue damage in rat models of both mild and severe acute pancreatitis (AP), indicating their therapeutic efficacy.

Infusion of hcMSCs led to a decrease in inflammatory mediators and an increase in regulatory T cells (Foxp3+), suggesting a mechanism of action that involves modulating the immune response to promote healing in pancreatic tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human bone marrow-derived clonal mesenchymal stem cells inhibit inflammation and reduce acute pancreatitis in rats. Jung, KH., Song, SU., Yi, T., et al.[2022]

Co-transplanting mesenchymal stromal cells (MSCs) with islets significantly improved glucose control in a mouse model of diabetes, particularly when islets were placed under the kidney capsule, indicating a potential strategy to enhance islet transplant outcomes.

The MSCs reduced early islet cell death (apoptosis) and improved islet survival, suggesting that MSCs may provide protective effects during the critical early post-transplant period, although they did not increase beta cell proliferation or differentiate into beta cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesenchymal stromal cells improve transplanted islet survival and islet function in a syngeneic mouse model. Borg, DJ., Weigelt, M., Wilhelm, C., et al.[2021]

The combination of bone marrow-derived mesenchymal stem cells (MSCs) and Icariin significantly promotes the regeneration of pancreatic acinar cells in rats with chronic pancreatitis, as evidenced by improved histopathological outcomes and reduced inflammatory markers.

Icariin enhances the proliferation of MSCs and together they effectively regulate key molecular factors involved in tissue repair, leading to a notable decrease in pro-inflammatory cytokines and collagen levels, indicating a potential therapeutic strategy for chronic pancreatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Icariin Promote Stem Cells Regeneration and Repair Acinar Cells in L-arginine / Radiation -Inducing Chronic Pancreatitis in Rats. Moustafa, EM., Moawed, FSM., Abdel-Hamid, GR.[2022]

Bone marrow mesenchymal stem cells (bmMSCs) significantly enhance insulin secretion and maintain the activity of transplanted islets when co-cultured, indicating their potential to improve islet survival.

In a rat model of severe acute pancreatitis, combined injection of bmMSCs via tail vein and intraperitoneal routes effectively reduced inflammation and pancreatic injury compared to other injection methods, suggesting a promising therapeutic approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protective Effects of Bone Marrow-Derived Mesenchymal Stem Cells on Insulin Secretion and Inflammation in the Treatment of Severe Acute Pancreatitis in Rats. Dong, H., Wang, Z., Chen, Y., et al.[2020]

Bone marrow mesenchymal stem cells (bmMSCs) significantly reduced pancreatic injury and associated lung damage in a rat model of acute pancreatitis, as evidenced by lower levels of inflammatory cytokines and improved pancreatic histology.

The protective effects of bmMSCs are linked to their ability to regulate the release of inflammatory cytokines through the NF-κB p65 signaling pathway, although they do not actively migrate to the inflamed pancreas but are passively trapped in related organs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of bone marrow mesenchymal stem cells in L-arg-induced acute pancreatitis: effects and possible mechanisms. Yin, G., Hu, G., Wan, R., et al.[2022]

Cotransplantation of autologous bone marrow-derived mesenchymal stem cells (MSCs) with islets in chronic pancreatitis patients showed no adverse events related to MSC infusions, indicating safety in this approach.

Patients receiving MSCs required less insulin and had better glycemic control, with lower fasting blood glucose levels and smaller declines in C-peptide, suggesting that MSC cotransplantation may enhance islet engraftment and improve overall outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous Mesenchymal Stem Cell and Islet Cotransplantation: Safety and Efficacy. Wang, H., Strange, C., Nietert, PJ., et al.[2023]

The study investigated the use of mesenchymal stem cell (MSC) transplantation in rat models of acute and chronic pancreatitis to understand their potential for regenerating damaged pancreatic tissue.

Allogeneic MSCs were administered at doses of 2 x 10^6 and 5 x 10^6 cells, aiming to evaluate both the beneficial and adverse effects of these cells on pancreatic tissue recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Mesenchymal stromal cells transplantation in acute and chronic pancreatitis in rats]. Lazebnik, LB., Trubitsyna, IE., Agafonov, MA., et al.[2012]

Mesenchymal stem cells (MSCs) derived from human pancreas exhibit a high potential for ex vivo expansion, capable of doubling in population every 30 hours and maintaining their characteristics over 30 passages, indicating their robustness for research and therapeutic applications.

These pancreatic MSCs can differentiate into multiple lineages, including osteogenic, adipogenic, and chondrogenic, demonstrating their versatility and potential for use in tissue engineering and regenerative medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Identification and isolation of mesenchymal stem cells from human fetal pancreas]. Hu, Y., Wang, QY., Ma, L., et al.[2006]

References

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

Human bone marrow-derived clonal mesenchymal stem cells inhibit inflammation and reduce acute pancreatitis in rats. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Mesenchymal stromal cells improve transplanted islet survival and islet function in a syngeneic mouse model. [2021]

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

Icariin Promote Stem Cells Regeneration and Repair Acinar Cells in L-arginine / Radiation -Inducing Chronic Pancreatitis in Rats. [2022]

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

Protective Effects of Bone Marrow-Derived Mesenchymal Stem Cells on Insulin Secretion and Inflammation in the Treatment of Severe Acute Pancreatitis in Rats. [2020]

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

Role of bone marrow mesenchymal stem cells in L-arg-induced acute pancreatitis: effects and possible mechanisms. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Autologous Mesenchymal Stem Cell and Islet Cotransplantation: Safety and Efficacy. [2023]

7. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Mesenchymal stromal cells transplantation in acute and chronic pancreatitis in rats]. [2012]

8. China pubmed.ncbi.nlm.nih.gov

[Identification and isolation of mesenchymal stem cells from human fetal pancreas]. [2006]