Neovascularized implantable cell homing encapsulation platform with tunable local immunosuppressant delivery for allogeneic cell transplantation (2024)

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thamer hani

Abstract The organs or cells transplantation is well-established in clinics. However, despite the increasing success rates and the broadening of various transplantation techniques, a key challenge is the requirement of life-long systemic immunosuppression to prevent rejection. Therefore, it is necessary to develop novel immuno-engineering strategies that can overcome the drawbacks of conventional immune cell depletion or immunosuppressive agents. In recent years, engineered biomaterials have been expanded toward localized and controlled release of immunomodulatory agents to decrease the effective dose and frequency of drug administration, mainly through immuno-engineering at the transplantation site. In this review, we concisely address a general overview of mechanisms involved in immune tolerance and rejection, followed by challenges within current therapeutic regimens, and then discuss recent developments on potent biomaterial-based immunoengineering strategies to prolong graft survival.

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Steffen Cosson, Bernard Schneider

The rapid increase in the number of approved therapeutic proteins, including recombinant antibodies, for diseases necessitating chronic treatments raises the question of the overall costs imposed on healthcare systems. It is therefore important to investigate alternative methods for recombinant protein administration. The implantation of genetically engineered cells is an attractive strategy for the chronic long-term delivery of recombinant proteins. Here, we have developed a high-capacity cell encapsulation system for the implantation of allogeneic myoblasts, which survive at high density for at least one year. This flat sheet device is based on permeable polypropylene membranes sealed to a mechanically resistant frame which confine cells seeded in a tailored biomimetic poly(ethylene glycol) (PEG)-based hydrogel matrix. In order to quantitate the number of cells surviving in the device and optimize initial conditions leading to high-density survival, we implant devices containing C2C12 mouse myoblasts expressing a luciferase reporter in the mouse subcutaneous tissue. We show that initial cell load, hydrogel stiffness and permeable membrane porosity are critical parameters to achieve long-term implant survival and efficacy. Optimization of these parameters leads to the survival of encapsulated myogenic cells at high density for several months, with minimal inflammatory response and dense neovascularization in the adjacent host tissue. Therefore, this encapsulation system is an effective platform for the implantation of genetically engineered cells in allogeneic conditions, which could be adapted to the chronic administration of recombinant proteins.

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Neovascularized implantable cell homing encapsulation platform with tunable local immunosuppressant delivery for allogeneic cell transplantation (2024)
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