AMSC for Kidney Failure

Overseen By Reagan Dukes

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Houssam Farres, M.D.

Must not be taking: Immunosuppressants, Investigational drugs

Disqualifiers: Malignancy, Immunodeficiency, Hypercoagulable, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Immediate (during procedure)

15 Participants Needed

Trial Summary

What is the purpose of this trial?

Researchers are evaluating the safety of allogeneic Adipose Derived Mesenchymal Stem Cells (AMSC) use during hemodialysis arteriovenous fistula and arterial bypass creation and its efficacy on improving access maturation and primary anastomotic patency.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial staff to get a clear answer.

What data supports the effectiveness of the treatment Adipose Derived Mesenchymal Stem Cells for kidney failure?

Research shows that adipose-derived mesenchymal stem cells (ADMSCs) can improve kidney function and reduce kidney damage in various experimental models, including those with chronic kidney damage and acute kidney injury. These stem cells have been found to help protect the kidneys and slow down the progression of kidney disease in animal studies. ^{1 2 3 4 5}

Is AMSC treatment safe for humans?

Research shows that adipose-derived mesenchymal stem cells (AMSCs) are generally safe in humans. In a study with chronic kidney disease patients, only mild side effects like slow speech and mild cognitive slowing were reported, and no serious or fatal adverse events were linked to the treatment. Another study confirmed no significant toxicity and showed improvements in kidney function, suggesting AMSCs are well-tolerated. ^{1 2 6 7 8}

How is the treatment with Adipose Derived Mesenchymal Stem Cells (ADMSCs) for kidney failure different from other treatments?

The treatment with Adipose Derived Mesenchymal Stem Cells (ADMSCs) is unique because it uses stem cells from fat tissue to help repair kidney damage and reduce fibrosis (scarring), which is not typically addressed by standard treatments. This approach focuses on regenerating kidney tissue and modulating the body's inflammatory response, offering a novel way to potentially slow or reverse kidney disease progression. ^{1 4 5 6 9}

Research Team

Houssam Farres, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for adults aged 18-85 with chronic kidney failure who need a new hemodialysis access point and have a life expectancy of over 2 years. Participants must be able to follow the study plan, give informed consent, and women must be unable to bear children or post-menopausal. People can't join if they've been in another drug/device study recently, have active infections, cancer treatments within 6 months, immune system problems like HIV/AIDS or autoimmune diseases, or a history of blood clotting issues.

Inclusion Criteria

I can communicate clearly, understand the study, and follow all procedures.

I am scheduled for a procedure to create a vein-artery connection in my arm.

You are expected to live for at least 2 years.

Exclusion Criteria

I have not had cancer or cancer treatment in the last 6 months.

I am currently being treated for an active infection.

Treatment with any investigational drug/ device within 60 days prior to study entry or Any other condition which in the judgment of the investigator would preclude adequate evaluation of the safety and efficacy of AMSCs and the AVF

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Adipose Derived Mesenchymal Stem Cells during the creation of a new upper extremity arteriovenous fistula

Immediate (during procedure)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Adipose Derived Mesenchymal Stem Cells

Trial Overview The trial is testing the safety and effectiveness of injecting Adipose Derived Mesenchymal Stem Cells (AMSC) during surgery to create an arteriovenous fistula for dialysis. The goal is to see if AMSCs help the new connection mature better and stay open without blockages.

Participant Groups

Group I: Adipose Derived Mesenchymal Stem Cells Experimental Treatment 1 Intervention

Subjects diagnosed with End Stage Renal Disease (ESRD) and are currently on hemodialysis therapy with planned creation of a new upper extremity arteriovenous fistula will receive Adipose Derived Mesenchymal Stem Cells treatment.

Adipose Derived Mesenchymal Stem Cells is already approved in United States, European Union for the following indications:

Approved in United States as Adipose Derived Mesenchymal Stem Cells for:

• Orthopedic conditions
• Degenerative disc disease
• Arthritis
• Musculoskeletal issues
• Diabetes mellitus type 1 and 2
• Ischemic stroke
• Multiple sclerosis
• Myocardial ischemia
• Coronary arteriosclerosis
• Limb ischemia
• Obesity
• Fatty liver disease
• Muscular dystrophy
• Osteoarthritis
• Crohn's disease
• Cancers
• Acute kidney injury
• Chronic skin wounds
• Glioma

Approved in European Union as Adipose Derived Mesenchymal Stem Cells for:

• Orthopedic conditions
• Degenerative disc disease
• Arthritis
• Musculoskeletal issues
• Diabetes mellitus type 1 and 2
• Ischemic stroke
• Multiple sclerosis
• Myocardial ischemia
• Coronary arteriosclerosis
• Limb ischemia
• Obesity
• Fatty liver disease
• Muscular dystrophy
• Osteoarthritis
• Crohn's disease
• Cancers
• Acute kidney injury
• Chronic skin wounds
• Glioma

Who Is Running the Clinical Trial?

Houssam Farres, M.D.

Lead Sponsor

Trials

1

Recruited

20+

Albert Hakaim

Lead Sponsor

Trials

1

Recruited

20+

Findings from Research

In a study involving male Wistar rats with chronic kidney injury induced by adenine, treatment with human adipose tissue-derived stem cells (hADSCs) significantly reduced kidney fibrosis and improved kidney function as indicated by lower serum and urine levels of urea and creatinine.

The hADSC therapy also decreased the expression of several fibrotic and inflammatory markers in the kidneys, suggesting a mechanism by which these stem cells promote kidney repair and reduce damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human adipose derived stem cells regress fibrosis in a chronic renal fibrotic model induced by adenine. Rivera-Valdés, JJ., García-Bañuelos, J., Salazar-Montes, A., et al.[2018]

Adipose-derived mesenchymal stem cells (AD-MSC) significantly protect against kidney injury caused by 45 minutes of renal ischemia followed by 48 hours of reperfusion in rats, as evidenced by improved serum creatinine and blood urea nitrogen levels.

Histological analysis revealed that AD-MSC treatment reduced tubular necrosis and other signs of kidney damage, indicating their potential as a therapeutic intervention for acute kidney injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of adipose-derived mesenchymal stem cells on renal function and histopathology in a rat model of ischemia-reperfusion induced acute kidney injury. Changizi-Ashtiyani, S., Hafazeh, L., Ghasemi, F., et al.[2022]

Transplanting adipose-derived mesenchymal stem cell (ASC) sheets directly into the kidneys of diabetic nephropathy (DN) rats resulted in better therapeutic outcomes compared to intravenous administration, as indicated by lower levels of albuminuria and urinary tumor necrosis factor-α.

The ASC sheets remained viable for 14 days post-transplantation and helped maintain renal structure, suggesting that this method enhances engraftment and could be a promising treatment for DN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transplantation of adipose-derived mesenchymal stem cell sheets directly into the kidney suppresses the progression of renal injury in a diabetic nephropathy rat model. Takemura, S., Shimizu, T., Oka, M., et al.[2022]

A single intravenous infusion of adipose-derived mesenchymal stem cells (Ad-MSCs) significantly improved kidney structure and function in mice with acute kidney injury induced by cisplatin, leading to better survival rates.

The treatment resulted in reduced inflammation and fibrosis, as indicated by decreased levels of inflammatory markers (TNF-α and TGF-β1) and improved kidney tissue morphology, demonstrating the potential of Ad-MSCs as a therapeutic strategy for kidney regeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of Renal Parenchyma in Response to Allogeneic Adipose-Derived Mesenchymal Stem Cells Transplantation in Acute Kidney Injury. Begum, S., Ahmed, N., Mubarak, M., et al.[2022]

Adipose-derived stem cells (ADSCs) isolated from renal adipose capsules proliferate faster and in greater numbers compared to those from groin adipose tissues, suggesting they are a more effective source for potential kidney disease treatments.

The study found that renal ADSCs have a lower expression of CD44 compared to groin ADSCs, indicating distinct biological characteristics that may influence their therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Study on the biological characteristics of adipose stem cells derived from renal adipose capsule cultured in vitro]. Wu, W., Zheng, HG., Zhang, DW., et al.[2010]

In a rat model of chronic kidney disease (CKD), adipose tissue-derived mesenchymal stem cells (AD-MSCs) significantly reduced plasma creatinine levels and markers of kidney damage, indicating improved renal function.

AD-MSCs also enhanced the expression of proteins associated with kidney regeneration, such as Pax-2, BMP-7, and VEGF, suggesting their potential as a therapeutic option for CKD due to their availability and less invasive collection method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human mesenchymal stem cells derived from adipose tissue reduce functional and tissue damage in a rat model of chronic renal failure. Villanueva, S., Carreño, JE., Salazar, L., et al.[2022]

The phase I clinical trial involving 12 chronic kidney disease (CKD) patients showed that a single intravenous dose of allogeneic adipose tissue-derived stem cells (ADSCs) was well tolerated, with only minor treatment-related adverse events reported, indicating a favorable safety profile.

Preliminary efficacy results revealed that 58% of participants experienced an increase in their kidney function (eGFR) by Week 24, suggesting that ADSCs may have potential benefits for improving kidney function in CKD patients, although no significant reduction in proteinuria was observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic adipose tissue-derived stem cells ELIXCYTE® in chronic kidney disease: A phase I study assessing safety and clinical feasibility. Zheng, CM., Chiu, IJ., Chen, YW., et al.[2022]

In a dose escalation study involving 21 subjects, adipose-derived human mesenchymal stem cell (MSC) therapy showed no significant cellular or renal toxicity, indicating a favorable safety profile.

The therapy led to improvements in renal oxygenation and glomerular filtration rate, along with a reduction in inflammatory markers, suggesting potential efficacy in treating renovascular disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving human kidney function in renovascular disease with mesenchymal stem cell therapy. Sivanathan, KN., Coates, PT.[2020]

Adipose tissue-derived stem cells (ASCs) significantly reduce kidney dysfunction and fibrosis when administered shortly after renal injury, as shown in a mouse model where ASCs improved kidney size and reduced collagen deposition within 24 hours of treatment.

Even when administered 6 weeks after injury, ASCs still improved kidney function and reduced fibrosis, indicating their potential for therapeutic use in established kidney damage by modulating inflammation and reducing hypoxia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adipose tissue-derived stem cell treatment prevents renal disease progression. Donizetti-Oliveira, C., Semedo, P., Burgos-Silva, M., et al.[2016]

References

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

Human adipose derived stem cells regress fibrosis in a chronic renal fibrotic model induced by adenine. [2018]

2. Iran pubmed.ncbi.nlm.nih.gov

The effect of adipose-derived mesenchymal stem cells on renal function and histopathology in a rat model of ischemia-reperfusion induced acute kidney injury. [2022]

3. Japan pubmed.ncbi.nlm.nih.gov

Transplantation of adipose-derived mesenchymal stem cell sheets directly into the kidney suppresses the progression of renal injury in a diabetic nephropathy rat model. [2022]

4. Korea (South) pubmed.ncbi.nlm.nih.gov

Modulation of Renal Parenchyma in Response to Allogeneic Adipose-Derived Mesenchymal Stem Cells Transplantation in Acute Kidney Injury. [2022]

5. China pubmed.ncbi.nlm.nih.gov

[Study on the biological characteristics of adipose stem cells derived from renal adipose capsule cultured in vitro]. [2010]

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

Human mesenchymal stem cells derived from adipose tissue reduce functional and tissue damage in a rat model of chronic renal failure. [2022]

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

Allogeneic adipose tissue-derived stem cells ELIXCYTE® in chronic kidney disease: A phase I study assessing safety and clinical feasibility. [2022]

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

Improving human kidney function in renovascular disease with mesenchymal stem cell therapy. [2020]

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

Adipose tissue-derived stem cell treatment prevents renal disease progression. [2016]