Cell-Based Therapy for Fibrosing Interstitial Lung Diseases, Current Status, and Potential Applications of iPSC-Derived Cells

Abstract

Fibrosing interstitial lung diseases (FILDs), e.g., due to idiopathic pulmonary fibrosis (IPF), are chronic progressive diseases with a poor prognosis. The management of these diseases is challenging and focuses mainly on the suppression of progression with anti-fibrotic drugs. Therefore, novel FILD treatments are needed. In recent years, cell-based therapy with various stem cells has been investigated for FILD, and the use of mesenchymal stem cells (MSCs) has been widely reported and clinical studies are also ongoing. Induced pluripotent stem cells (iPSCs) have also been reported to have an anti-fibrotic effect in FILD; however, these have not been as well studied as MSCs in terms of the mechanisms and side effects. While MSCs show a potent anti-fibrotic effect, the possibility of quality differences between donors and a stable supply in the case of donor shortage or reduced proliferative capacity after cell passaging needs to be considered. The application of iPSC-derived cells has the potential to overcome these problems and may lead to consistent quality of the cell product and stable product supply. This review provides an overview of iPSCs and FILD, followed by the current status of cell-based therapy for FILD, and then discusses the possibilities and perspectives of FILD therapy with iPSC-derived cells.

Keywords

• fibrosing interstitial lung diseases (FILDs)
• idiopathic pulmonary fibrosis (IPF)
• fibrotic hypersensitivity pneumonitis (fHP)
• induced pluripotent stem cells (iPSCs)
• alveolar type 2 epithelial cells (AT2s)
• mesenchymal stem cells (MSCs)