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Anti-fibrotic materials for immunoprotected cell-based therapies

Presented at: Bioprocessing 2021
C.E. Credits: P.A.C.E. CE Florida CE
Speaker
  • Post-doctoral Fellow Boston Children's Hospital - Harvard; Affiliate researcher - MIT
    Biography

      Matt Bochenek received his BS in Industrial and Enterprise Systems Engineering from the University of Illinois Urbana/Champaign. His interest in biological systems made him alter his focus, and he pursued a Ph.D. in Bioengineering at the University of Illinois at Chicago (UIC).  Here, he worked with Dr. Jose Oberholzer in a Phase III clinical trial for intraportal islet transplantation. This entails isolating insulin producing islet cells from human donor pancreata and transplanting them intraportally into Type I diabetic patients in order to restore glycemic control. Currently, he works as a senior post-doc in Dr. Dan Anderson and Dr. Bob Langer labs at MIT. and works for cell and. Matt's work primarily focuses on the development of immunomodulatory biomaterials, specifically for the immuno-protection of islet cells and other cell-based therapies, as well for cancer therapies. Recently, he published in Nature BME to show that anti-fibrotic alginate modified materials can protect islet cells in non-human primates for up to 4 months without the need for immunosuppression.


    Abstract

    Cell encapsulation within semi-permeable devices represents a local immunoisolation strategy for cell-based therapies without the need for systemic immunosuppression. The encapsulation system allows for the diffusion of nutrients into the device which are important for cell survival, and the therapeutic payload produced by the cells to diffuse out in order to regulate the disease of choice. The barrier provided by the semi-permeable membrane prevents the entrance of immune cells that would otherwise destroy the therapeutic cells. For some time, encapsulation strategies have been applied to insulin producing islets of Langerhans transplantation and have shown long-term diabetes correction in many rodent models. However, these same strategies have failed when applied to a small number of clinical trials with diabetic patients. The foreign body response (FBR) to the biomaterials comprising the devices has been the major issue when testing in larger animal models. FBR results in the deposition of a dense ECM and cellular network covering the devices that restricts nutrition of the cells inside and compromises viability. Our lab is developing novel biomaterials and drug delivery strategies that can resist the foreign body response and fibrosis of implantable materials. Without fibrosis covering these encapsulation devices, free nutritional exchange for the therapeutic cells inside ensures continued secretion of their therapeutic payload for regulation of the disease of interest. This talk will discuss the discovery of a number of immune modulatory materials that have been developed in the Anderson/Langer lab that can reduce fibrotic activation and can lead to the protection of allogeneic islets in non-human primates for up to 4 months without any immune suppression.

    Learning Objectives:

    1. What is the major contributor to the failure of immunoisolated cell therapy devices in patients

    2. Identify key immune cell types for immunomodulatory biomaterials


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