Innate Immune-Cloaked Microgel-Coated Mesenchymal Stromal Cells Reverse Persistent Pulmonary Fibrosis via Reparative
Ik Sung Cho1,2, Amal Yaghmour1,2, Akshay Joshi1,2,3
1Department of Pharmacology and Regenerative Medicine, University of Illinois at Chicago, Chicago, IL, 60612, USA.
Advanced Materials (Deerfield Beach, Fla.)
|September 23, 2025
Summary
Engineered mesenchymal stromal cells evade immune clearance using a CD47 agonist coating. These cells reverse lung fibrosis by modulating macrophages, creating a living pharmacy for tissue repair.
Area of Science:
- Biomaterials Science
- Immunology
- Regenerative Medicine
Background:
- The innate immune system presents challenges for therapeutic delivery and can exacerbate tissue damage.
- Fibrosis, a complex chronic disease, requires innovative treatment strategies that modulate immune responses.
Purpose of the Study:
- To develop an innate immune checkpoint material-based strategy for treating fibrosis.
- To engineer mesenchymal stromal cells for immune evasion and therapeutic delivery.
Main Methods:
- Mesenchymal stromal cells were coated with a microgel and functionalized with a CD47 agonist to evade macrophage clearance.
- The efficacy of these engineered cells in reversing fibrotic damage was assessed in lung tissue.
- Single-cell RNA sequencing was employed to identify mediating immune cell populations.
Main Results:
- Engineered cells successfully evaded clearance by tissue-resident macrophages.
- The cells demonstrated reversal of persistent fibrotic lung damage via a paracrine mechanism.
- A transitional antigen-presenting macrophage subpopulation was identified as crucial for reparative effects.
Conclusions:
- An innate immune checkpoint strategy using engineered cells offers a novel approach for treating chronic fibrotic diseases.
- Combining immune cloaking with local signaling enables the design of secretory cells for long-term tissue remodeling.
- This approach establishes a 'living pharmacy' for managing chronic tissue damage.
