Idiopathic Pulmonary Fibrosis (IPF) is a rapidly progressing, irreversible, and fatal lung disease. As the disease advances, persistent injury causes healthy lung tissue to be gradually replaced by fibrotic tissue, resulting in a continuous decline in pulmonary function. Current clinical treatments primarily aim to slow disease progression, and effective therapies capable of truly regenerating and repairing lung tissue remain lacking.

Airway basal stem cells (BCs) are considered the most important regenerative cell source in the adult lung. Based on this scientific foundation, the Regend Therapeutics team has developed REGEND001, the world’s first autologous airway basal stem cell therapy. Completed Phase II clinical data demonstrate that this regenerative approach has shown remarkable efficacy in repairing damaged lung structures, alleviating tissue fibrosis, and improving both pulmonary function and patients’ quality of life. Building on these achievements, the team continues to advance new product development while optimizing and iterating next-generation technologies.

On January 9, 2026, Regend Therapeutics, in collaboration with the Tongji University School of Medicine / Shanghai East Hospital and Nanchang University, published a research article titled “Control of airway basal stem cells-mediated lung repair by TGF-β signaling” on the homepage of Science Advances. The study proposes an entirely new solution: genetically engineering stem cells to endow them with the ability to sense their environment and respond autonomously, enabling repair programs to be activated at the appropriate time and location.

Professor Wei Zuo of Tongji University and Dr. Ting Zhang of the Super Organ Research Center at Regend Therapeutics served as co-corresponding authors, while Academician Yeguang Chen of Nanchang University was the senior author.

The study found that during lung injury and fibrosis, signaling within lung tissue is not chaotic; rather, a gradient of TGF-β signaling gradually intensifies from healthy airways toward diseased regions. Although this signal has long been regarded as a key driver of fibrosis, multi-omics analyses conducted by the research team revealed that airway basal stem cells rely on this TGF-β gradient to determine the spatial location where repair is needed.

Through conditional knockout of the TGF-β type II receptor and Smad4, as well as experiments involving targeted protein degradation (PROTAC), the researchers confirmed that under precise regulation of the TGF-β/SMAD signaling pathway, airway basal stem cells exhibit highly ordered behavioral patterns: remaining quiescent and maintaining homeostasis in regions with low TGF-β signaling; becoming activated in high-signal regions to initiate proliferation and directed migration; and ultimately differentiating into alveolar epithelial cells to participate in the repair of damaged alveolar structures. These findings suggest that TGF-β is not merely a “pathogenic signal,” but rather a critical informational “navigation system” guiding lung tissue repair.

Building on this mechanistic insight, the team further engineered intelligent, responsive airway basal stem cells (iBMP7-BCs). The core logic of this cellular system is as follows:

·       The cells remain “silent” when located in healthy lung tissue;

·       They are automatically activated upon entering fibrotic lesions and sensing elevated TGF-β signals;

·       They then directionally secrete the anti-fibrotic factor BMP7, enabling precise therapeutic repair.

Within this system, TGF-β acts as the activation “switch” for intelligent cells, while BMP7 functions as an on-demand “repair tool.” Study results show that, compared with traditional cell therapy strategies, iBMP7-BCs significantly reduce the severity of pulmonary fibrosis, markedly improve lung tissue structure, and effectively enhance lung function in mouse models.

The “dynamic intelligent cell” concept proposed in this research breaks away from the conventional static treatment paradigm in which engineered cells continuously and indiscriminately release therapeutic factors. Instead, it emphasizes real-time sensing, feedback regulation, and precise responsiveness between therapeutic cells and the lesion microenvironment.

The research team noted that future work will focus on further evaluating long-term safety and efficacy while accelerating the clinical translation of a universal “intelligent stem cell” pipeline, with the goal of providing an entirely new therapeutic strategy for IPF and other major respiratory diseases.

This work was supported by the National Key R&D Program for Stem Cells and Organ Repair, the National Biotechnology Innovation Center's “Open Call” Cell Therapy Initiative, special funding from the Jiangsu Provincial Science and Technology Program, and research funding from Regend Therapeutics.

Full article:
https://www.science.org/doi/10.1126/sciadv.adz1519