Development of a bioactive microencapsulation platform incorporating decellularized extracellular matrix to entrap human induced pluripotent stem cells for versatile biomedical applications

Abstract

Human-induced pluripotent stem cells (hiPSCs) hold great promise in the fields of regenerative therapy and personalized in vitro tissue models as they provide an almost endless autologous source of virtually any cell type. Their potential benefits can be highly enhanced through polymeric cell microencapsulation, which offers the cells structural support and immune protection from the host tissue. However, in contrast to biologically-inert polymers, decellularized extracellular matrix (dECM)-based microencapsulation also provides the cells a physiologically mimetic bioactive microenvironment while providing reproducibility and scalability. Here we describe the entrapment of hiPSCs in a porcine pancreatic ECM (pECM)-based microencapsulation platform and address its key aspects. To promote high levels of cell survival and growth, several encapsulation parameters were optimized, including cell dissociation level, the process layout, and Rho-associated kinase (ROCK) inhibitor addition. This has allowed extensive proliferation of the cells for at least 21 days in vitro. Furthermore, the encapsulation of embryoid bodies (EBs) was assessed to address the entrapment of hiPSCs at various stages of differentiation, and the culture conditions that promote lasting encapsulated EB survival were investigated. Finally, to study the in vivo safety of dECM-encapsulated hiPSC-derived products, completely undifferentiated pECM-encapsulated hiPSCs were implanted in mice. The cells displayed a slower proliferation rate in vivo and showed no signs of cell escape from the microcapsules. Altogether, the results of this study point to the potential of dECM-based microencapsulation to provide an efficient polymeric platform for transplantation of hiPSC-derived products and the development of iPSC-based 3D tissue models.