Mesenchymal stromal cells (MSCs), known for their immunomodulatory and tissue repair potential, have been extensively explored in numerous clinical trials for various autoimmune diseases in recent years. However, the limited efficiency of effective homing and retention at lesion sites following systemic intravenous infusion results in insufficient target tissue accessibility, posing a critical bottleneck that constrains their therapeutic consistency and clinical translation. On January 22, 2026, the research team led by Professor Chen Lei from the School of Life Sciences at Southeast University, in collaboration with the team led by Associate Researcher Wang Yan from the Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, published a research paper online in Nature Communications titled "Antibody-conjugated mesenchymal stromal cell drug delivery system for the treatment of autoimmune diseases in mice." The study proposes a strategy termed the "Antibody-conjugated MSC Drug Delivery System (AcM-DDS)" for autoimmune diseases. This system, on one hand, utilizes bioorthogonal click chemistry to anchor antibodies onto the MSC membrane surface, enabling the recognition and connection to cells presenting specific antigens enriched in lesions. On the other hand, by loading drugs intracellularly, MSCs are transformed into actively migrating "living drug carriers," thereby achieving localized and targeted drug delivery.

Lesions in autoimmune diseases are often enriched with aberrantly activated CD4+ T cells, among which Th17 cells drive inflammation progression by secreting pro-inflammatory factors like IL-17A. The differentiation and function of Th17 cells are regulated by the key transcription factor RORγt. However, RORγt inverse agonists represented by Cedirogant have faced safety limitations in clinical development, necessitating more precise delivery strategies. Based on this, the study reports an application example of AcM-DDS: anchoring CD4 antibodies onto the membrane surface of bone marrow-derived MSCs (BMSCs) and loading them with Cedirogant-containing liposomes. This design aims to target CD4+ T cells while simultaneously inhibiting their differentiation into Th17 cells.

The therapeutic potential of AcM-DDS was validated in two mouse models of autoimmune diseases: the imiquimod-induced acute psoriasis-like inflammation (IMQ) model and the collagen-induced chronic arthritis (CIA) model. In the IMQ model, AcM-DDS demonstrated enhanced local anti-inflammatory effects, significantly downregulating the expression of IL-17A, RORγt, and various other inflammation-related factors such as IL-21, IL-22, G-CSF, and GM-CSF in skin lesions. In the CIA model, AcM-DDS further exhibited comprehensive improvement against chronic inflammation: only 1 out of 6 mice showed mild inflammation at the experimental endpoint, along with significant improvements in indicators like synovial inflammation in multiple joints, cartilage and bone destruction, and Th17 cell levels in the spleen.

Compared to genetically engineered MSCs, this antibody-conjugated MSC approach is simpler to construct and allows rapid "target switching"—theoretically, it could be extended to different cells/diseases simply by changing the antibody. Recent years have also witnessed regulatory milestones for MSC therapies: On December 18, 2024, the U.S. FDA approved Ryoncil for the treatment of steroid-refractory acute graft-versus-host disease (aGVHD) in children, marking the first approved MSC therapy in the U.S. On January 2, 2025, China's National Medical Products Administration conditionally approved the marketing of Remestemcel-L injection for steroid-refractory aGVHD. These advancements highlight the clinical value of MSCs in immunomodulation and also provide a broader application landscape for the future expansion of AcM-DDS to immune diseases such as aGVHD and atopic dermatitis. The antibody-conjugated stem cell technology detailed in the paper has been granted a national invention patent. Leveraging this technology, the team has developed a precision therapy platform based on antibody-conjugated mesenchymal stem cells, which was awarded the Third Prize in the 2025 Jiangsu Province "Chuang Qing Chun" Biomedical Industry Chain Competition.

Professor Chen Lei from Southeast University, Associate Investigator Wang Yan, and Assistant Investigator Xie Qian from the Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, are the co-corresponding authors of the paper. This research received support from the National Key R&D Program of China, the National Natural Science Foundation of China, the Natural Science Foundation of Jiangsu Province, and the Major Science and Technology Special Project of Shenzhen.