Tongxie Yaofang enhances the homing efficiency of exogenous bone marrow-derived mesenchymal stem cells to the colonic mucosa and alleviates ulcerative colitis

Abstract

BACKGROUND

Bone marrow-derived mesenchymal stem cells (BMSCs) are a promising therapy for ulcerative colitis (UC). However, their clinical benefit is limited by inefficient homing to the inflamed colonic mucosa. Improving the migration of BMSCs to sites of intestinal inflammation remains a key challenge in the development of cell-based treatments for UC. Tongxie Yaofang (TXYF), a traditional Chinese medicine formula, has been shown to relieve symptoms in UC patients. Our previous in vitro studies also showed that TXYF enhances the migratory capacity of BMSCs. However, whether TXYF enhances the therapeutic effect of BMSCs transplantation in UC, and the mechanisms involved, remain unclear.

AIM

To determine whether TXYF promotes the homing of BMSCs and improves experimental colitis, and to explore the underlying mechanisms.

METHODS

BMSCs from Sprague-Dawley rats were characterized via flow cytometry, and TXYF’s effects on migration were evaluated using scratch and Transwell assays. In a colitis model, the synergistic efficacy of TXYF and BMSCs was assessed through disease activity index, histology, immunohistochemistry, tracing, reverse transcription-quantitative polymerase chain reaction, and western blotting. Furthermore, the stromal cell-derived factor 1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4) axis was investigated using specific antagonists to elucidate the molecular mechanisms of this combinatorial therapy.

RESULTS

TXYF promoted the in vitro migration of BMSCs. In vivo, the combination of TXYF with BMSCs transplantation alleviated colitis symptoms in rats, improving inflammatory responses, colonic tissue damage, and mucosal barrier function. Our findings suggest that TXYF may enhance the migratory capacity of BMSCs by modulating the SDF-1/CXCR4 axis, thereby increasing their homing to the colonic mucosa.

CONCLUSION

This study demonstrates that TXYF can enhance the homing efficiency of exogenous BMSCs to the colonic mucosa, likely through the SDF-1/CXCR4 axis, which contributes to the mitigation of experimental colitis.

Keywords: Ulcerative colitis; Tongxie Yaofang; Bone marrow-derived mesenchymal stem cells; Stromal cell-derived factor 1; C-X-C motif chemokine ligand 12; C-X-C chemokine receptor type 4; Inflammatory bowel disease; Intestinal mucosal barrier; Traditional Chinese medicine; Migration

Core Tip: Bone marrow-derived mesenchymal stem cells (BMSCs) are a promising therapy for ulcerative colitis (UC). However, their clinical use is limited by poor homing to the colonic mucosa. Tongxie Yaofang (TXYF) is a traditional Chinese medicine formula. Our findings indicate that TXYF enhances the homing of BMSCs to the colonic mucosa and ameliorates symptoms of UC. This effect appears to involve modulation of the stromal cell-derived factor 1/C-X-C chemokine receptor type 4 axis. These findings suggest that TXYF may serve as an adjunct strategy to improve the efficacy of BMSCs-based therapy for UC.