Using stem cells to improve dialysis access for kidney disease patients
The therapeutic benefits of mesenchymal stem cells have been harnessed to reduce vein narrowing and inflammation that occur after arteriovenous fistula creation, a crucial procedure for hemodialysis in end-stage kidney failure patients.
Researchers at the Mayo Clinic (MN, USA) have used mesenchymal stem cells (MSCs) to prevent inflammation and vein narrowing in dialysis blood vessels. By harnessing the therapeutic potential of MSCs, they demonstrated improved blood vessel healing, which could enhance dialysis effectiveness for kidney disease patients and delay the need for a kidney transplant.
Patients with end-stage kidney disease often undergo dialysis as a critical step before a kidney transplant becomes necessary. Hemodialysis, a common form of dialysis, uses a machine to filter waste, toxins and excess fluids from the blood, effectively taking over the kidney’s function. To facilitate this process, surgery is performed to create an arteriovenous fistula (AVF) by connecting an artery and a vein in the arm, allowing blood to flow through the vein for treatment. However, AVFs fail in over 60% of cases, often due to vein narrowing caused by inflammation, damage and poor healing. With more than 4 million people worldwide living with end-stage kidney disease, there is an urgent need for effective solutions to reduce vein narrowing and improve AVF outcomes, ensuring better access to effective treatment.
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To address this issue of vein narrowing following AVF, Sanjay Misra, senior author and interventional radiologist at Mayo Clinic, has been exploring stem cell therapies for various diseases. His lab is particularly focused on understanding the mechanisms behind the failure of hemodialysis grafts, which serve as permanent access point in the bloodstream for hemodialysis. Misra and his team homed in on the anti-inflammatory properties of MSCs, known for their ability to secrete growth factors that promote healing.
In this study, as part of a Phase I clinical trial, 21 patients with end-stage kidney failure underwent AVF surgery. Eleven of these patients were injected with their own fat-derived MSCs prior to the procedure, while the remaining 10 patients served as a control group and were not treated with MSCs. The team assessed the effects of MSCs on blood vessel tissue healing and AVF function, discovering that in some patients who received MSCs, the AVFs healed faster and were more durable.
“We were surprised by these differences in response to the [MSCs]. This spurred us to delve further into our research and include preclinical models and RNA sequencing technology,” says lead author Sreenivasulu Kilari.
To investigate why MSCs were able to reduce inflammation in AVFs, the researchers used animal models to study blood vessel healing. They found that the AVFs in the animal models treated with patient-derived MSCs had more immune cells (macrophages) and less abnormal tissue growth in the vein walls. These findings were supported by clinical outcomes, as after 42 months of follow-up, patients treated with MSCs had faster-developing AVFs with wider veins compared to controls.
Furthermore, gene analysis of these MSC-treated AVFs revealed lower levels of two inflammatory proteins (Pparγ and Lepr) and higher levels of a tissue repair protein (Ltbp2). To validate these findings, the researchers genetically removed Pparγ from immune cells in the animal models, which resulted in less vein narrowing and demonstrated that MSC treatment reduces the production of inflammatory proteins.
These specific genetic factors – particularly Pparγ and Lepr levels – could serve as biomarkers to predict which patients are most likely to benefit from MSC therapy, potentially enabling personalized treatment approaches for AVF patients. The research team plans to validate these promising results through larger clinical trials to gather more comprehensive data.
“This approach has the potential to improve outcomes for millions of patients with kidney failure, reduce healthcare costs and inform new clinical guidelines for dialysis access management if validated in larger clinical trials,” expressed Misra.
