Whole Organ Engineering for the clinical application of iPS cells

Recently, a regenerative approach using decellularization methods to create regenerative organs has been explored in small animal models. This method preserves the organ-specific three-dimensional extracellular matrix (ECM) which can be used as an acellular and transplantable native scaffold potentially providing an ideal microstructural cradle for cell attachment, differentiation and function. The preservation of the native ECM may also have a beneficial role in signaling and paracrine pathways for cell-to-cell and cell-to-matrix contacts by providing natural growth factors. Possibly even more important for survival and long-term function of reseeded cells, original vascular networks may be re-vascularized for rapid oxygen and nutrient transport by connecting to vessels in situ. For liver, this whole-organ decellularization and recellularization technology is envisioned as an alternative to a bridging therapy prior to liver transplantation, as well as a basic science model. In the present study, we sought to optimize the decellularization and recellularization technique in both small and large animal model using primary hepatocyte and non-parenchymal cells. In addition, human iPS derived hepatocyte like cells were introduced into the part of the decellularized scaffold and analyzed histochemically. The results suggested that administration of multiple cell sources into the decellularized liver scaffold enriched the microenvironment for factors related to hepatic regeneration and maintenance as well as protein production. We believe this new approach would be an option of the clinical application of iPS cell technology.