Abstract
Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease primarily affecting the elderly, marked by lung tissue scarring and impaired function. Current treatments, such as pirfenidone and nintedanib, slow disease progression but do not halt it and are associated with side effects. Lung transplantation is limited by donor shortages and surgical risks. Stem cell-based therapies, particularly mesenchymal stromal cells (MSCs) from bone marrow, adipose tissue, and umbilical cord, offer promise due to their low immunogenicity, homing capacity, and paracrine signaling. Preclinical models show that MSCs or their miRNA-bearing extracellular vehicles (EVs) can inhibit the TGFβ/Smad pathway, reprogram macrophage polarization, and promote tissue regeneration through anti-inflammatory and repair factors (e.g., IL-10, HGF, VEGF). Genetic modifications like CXCR4 overexpression may enhance MSC efficacy. Early clinical trials suggest favorable safety and preliminary efficacy, though long-term validation is needed. Additionally, alveolar type 2 (AT2) cells derived from induced pluripotent stem cells (iPSCs) and lung epithelial cells from embryonic stem cells (ESCs) offer potential for alveolar repair. Bioengineering advancements, including hydrogel scaffolds and 3D lung organoids, enhance stem cell retention and provide platforms for IPF research and drug screening. This review explores the therapeutic potential of stem cell therapies in IPF, integrating recent bioengineering developments and clinical prospects.