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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals with chronic pancreatitis (CP) who are scheduled for a specific surgery called TP-IAT, which involves removing the pancreas and transplanting islet cells. Participants will receive either an infusion of bone marrow-derived mesenchymal stem cells (special cells that can develop into different types of cells) or a placebo. The goal is to determine if these stem cells can improve outcomes after surgery. This trial may suit those diagnosed with CP, scheduled for the surgery, and managing diabetes with reasonable blood sugar levels. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that bone marrow-derived mesenchymal stem cells (BM-MSCs) might help treat pancreatitis, based on animal studies. These studies suggest that BM-MSCs can reduce issues like swelling and damage in the pancreas, indicating potential safety and effectiveness for humans.

Other studies have tested BM-MSCs for safety and efficacy, showing they can reduce pain in various conditions without major safety concerns. This suggests the treatment is generally safe for humans.

As this trial is in an early stage, researchers are primarily ensuring the treatment's safety. Although long-term data is not yet available, current results are promising. Participants in this trial are helping to confirm the safe use of BM-MSCs for chronic pancreatitis. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using mesenchymal stem cells (MSCs) for chronic pancreatitis because they offer a new way to support the pancreas. Unlike current treatments that mostly manage symptoms, MSCs can potentially repair and regenerate damaged pancreatic tissue. The infusion of bone marrow-derived MSCs, combined with islet cells, aims to improve pancreatic function more effectively. This approach is particularly promising because MSCs have anti-inflammatory properties and can modulate the immune response, which may lead to better long-term outcomes for patients with chronic pancreatitis.

What evidence suggests that this trial's treatments could be effective for chronic pancreatitis?

Research has shown that bone marrow-derived mesenchymal stem cells (BM-MSCs) could aid in treating pancreatitis. Animal studies suggest these cells protect the pancreas and reduce damage. BM-MSCs lower inflammation and stress, promoting pancreas healing. They also assist in forming new blood vessels in the damaged area, a process known as angiogenesis. In this trial, participants will receive either a one-time infusion of islets plus BM-MSCs at 20x10^6 or 50x10^6, or a placebo infusion of islets only. This approach could benefit individuals with chronic pancreatitis undergoing TP-IAT by improving healing and reducing complications. ^{1 2 4 6 7}

Who Is on the 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

Are You a Good Fit for This Trial?

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5878867/

Mesenchymal Stromal Cell Therapy for Pancreatitis Based on animal studies, adult mesenchymal stromal cells (MSCs) are promising for the treatment of pancreatitis.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8552371/

Curative role of mesenchymal stromal cells in chronic ... We evaluated the therapeutic effect of bone marrow-based mesenchymal stromal cell (BM-MSC) transplanted in rats to preserve tissue integrity and to restore ...

3. nature.com nature.com/articles/s41598-017-00629-3

Bone marrow-derived mesenchymal stem cells (BMSCs ... We demonstrate here that microRNA-9 (miR-9) modified BMSCs (pri-miR-9-BMSCs) can significantly reduce the pancreatic edema, infiltration, hemorrhage, necrosis.

4. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/450596

Safety and Efficacy of Mesenchymal Stem Cells Associated ... This protocol aims to test whether an infusion of allogeneic bone marrow-derived mesenchymal stromal cells (BM-MSCs) can reduce pain ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1465324918307059

Bone marrow–derived mesenchymal stromal cells ... Results. Our data showed that BMSCs significantly reduce inflammation and oxidative stress, reduce apoptosis and promote angiogenesis of damaged pancreas.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05925036

Novel Cellular Therapy for the Treatment of Pain ... The goal of this clinical trial is to test whether adult stem cells, called mesenchymal stem cells (MSCs) collected from the patient's bone marrow can help ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3608346/

Bone-Marrow-Derived Mesenchymal Stem Cells for Organ ... BMMSCs can effectively relieve injury to pancreatic acinar cells and small intestinal epithelium, promote the proliferation of enteric epithelium and repair of ...