Study Reports of the Ex Vivo Drug Delivery System for the Delivery of MSCs to Patients with Renal Impairment
Scientists are reporting promising results in the early stages of a clinical trial designed to assess the feasibility of a new type of treatment for people with acute kidney disease. Released in STEM CELLS Translational medicine, the study shows how mesenchymal stromal cells (MSCs) delivered using a novel ex vivo drug delivery system – SBI-101 – can keep MSCs viable longer and reprogram the peripheral immune response to the disease. organ repair.
Acute kidney failure occurs when a kidney is suddenly unable to filter the blood and allows dangerous levels of waste to build up. The most severe cases require dialysis or a kidney transplant. Unfortunately, acute kidney damage dependent on dialysis has a death rate of up to 50 to 70 percent.
Inflammation is a key factor behind this. In severe diseases, the mediators of inflammation go out of order, causing a “cytokine storm” leading to a vicious cycle of immunity that further damages the kidneys and other organs. Current treatments fail to comprehensively treat these underlying inflammatory processes.
“Rebalancing the inflammatory response with cell-based immunotherapy may offer a multifaceted approach to break the cycle and restore organ function after severe injury,” explained corresponding study author Biju Parekkadan, Ph. D., scientific co-founder of Sentien Biotechnologies, Inc., in Lexington, Mass. Sentien completed its first human study by working with multiple centers across the United States to test its SBI-101 product in a Phase 1b clinical trial.
MSCs secrete several types of molecules that modulate an immune cell’s response to inflammation and therefore have great potential for use in regenerative medicine. However, MSCs administered by the conventional intravenous route are usually filtered in the lungs and undetectable in the body soon after administration. “Given this rapid clearance, they might not be able to match the dose needed to have a lasting impact on a systemic immune response,” said Dr Parekkadan.
This pharmacological knowledge has led to the search for a more efficient method of administering MSCs. The innovation of SBI-101 therapy is the combination of “ready-to-use” MSCs and an FDA-approved blood filtration device to improve and control exposure to MSCs. This design allows the patient’s blood to be reprogrammed outside the body, in a device housing MSCs, thus maintaining their viability for the duration of treatment.
“This is because SBI-101 behaves like a CSM tissue that functions outside the body to detect inflammation in the patient’s bloodstream and respond with a natural blend of growth factors, cytokines, and chemokines. to normalize immune signaling and function, ”explained Dr. Parekkadan.
The phase 1 trial reported in MCTS was designed to test the safety, tolerability and pharmacology of SBI-101 in adults with life-threatening renal impairment who were already receiving dialysis. Sixteen patients were recruited for the study. Twelve were treated with SBI-101, along with their standard continuous renal replacement therapy (CCRT) regimen, while four received a sham SBI-101 with CRRT. The treatment period lasted at least 12 hours, and up to 24 hours. (CCRT is a slower form of dialysis that puts less stress on the heart. Treatment typically lasts 24 hours, compared to the four-hour dialysis routine. conventional dialysis.)
The evaluations were then carried out at intervals over a period of 28 days after treatment. They showed that MSCs were viable for the 24-hour dose by measuring the levels of secreted factors, verifying a longer treatment duration than the intravenous lines showed. In addition, SBI-101 promoted an immunotherapeutic response associated with reduced kidney damage by measuring surrogate biomarkers. No serious adverse reactions related to SBI-101 were observed.
“These early results suggest that SBI-101 may impact a peripheral immune response that can be transmitted to local tissue damage in vital organs, including the kidney. This important first step lays the groundwork for studying how this immunotherapy may impact patient outcomes in larger patient trials, ”concluded Dr. Parekkadan.
“This study highlights a potential clinical approach that could change outcomes for patients who have acute kidney disease and are dependent on dialysis,” said Anthony Atala, MD, editor-in-chief of STEM CELLS Translational medicine and director of the Wake Forest Institute for Regenerative Medicine. “These clinical trial results highlight the healing potential of mesenchymal stem cells and warrant further study.”
Swaminathan, M., et al. (2021) Pharmacological effects of ex vivo mesenchymal stem cell immunotherapy in patients with acute renal failure and underlying systemic inflammation. Stem cells Translational medicine. doi.org/10.1002/sctm.21-0043.