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Kidney Week

Abstract: SA-PO532

Ex Vivo MSC Therapy for Subjects with AKI

Session Information

Category: Acute Kidney Injury

  • 102 AKI: Clinical, Outcomes, and Trials

Author

  • Barcia, Rita N., Sentien Biotechnologies, Lexington, Massachusetts, United States
Background

Mesenchymal stromal cells (MSCs) are known to secrete potent molecules and extracellular vesicles contributing to immunomodulation and wound healing. There is a good deal of interest in MSC based approaches for the treatment of human kidney injury driven by evidence that MSCs repair the kidney by paracrine and endocrine mechanisms (Humphreys & Bonventre, 2008). Though clinical trials using MSCs as infusion therapeutics have been successful in demonstrating safety, clear clinical benefit has not consistently been realized. Lack of clinical effectiveness may be due to ineffective dosing of MSCs and short exposure times of the infused cells. Sentien Biotechnologies has pioneered a new way to control the delivery of MSC secreted factors by using an ex vivo cell therapy approach as a novel route of extracorporeal administration. Sentien’s lead product consists of a continuous flow bioreactor with MSCs immobilized on the extraluminal side of a hollow fiber membrane. Patient’s blood flows through the lumen of the hollow fibers and are conditioned by MSC secreted factors, allowing for the blood cells and MSCs to sense their environment and react to it.

Methods

In vitro studies were performed to assess MSC function within Sentien’s reactors. The technology was also tested as a continuous ex vivo therapy in an ischemia/reperfusion dog model of Acute Kidney Injury (AKI). Toxicological studies were performed in healthy dogs. A multi-center, randomized, placebo-controlled double-blind study of extracorporeal MSC therapy has begun in human subjects with AKI receiving continuous renal replacement therapy.

Results

In vitro studies showed that MSCs are viabile and responsive in the biorector. In a dog model of AKI, an increase in survival was observed in the treated animals. Additionally, toxicological studies verified a pharmacokinetic and pharmacodynamic response to MSCs that was consistent with a potent immunomodulatory mechanism of action. Preliminary results from the ongoing clinical trial will be presented.

Conclusion

Ex vivo MSC therapy using this reactor technology has promise for other clinical applications requiring systemic immunotherapy for tissue repair and regeneration.

Funding

  • NIDDK Support