Endomicroscopy Will Track Injected Mesenchymal Stem Cells in Rat Colitis Models
Ming Li1, Yi-Xin Zhang, Zhen Zhang
1*Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, China; and †Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas.
Background:
Mesenchymal stem cells (MSCs) have demonstrated significant potentials for the treatment of inflammatory bowel disease. Clinical feasible methods to individually document the MSC recruitment to intestinal mucosa is lacking. Here, we proposed that endomicroscopy could noninvasively track MSCs in vivo at cellular resolution.
Method:
Isolated Sprague Dawley rat MSC was characterized, fluorescently labeled, and imaged ex vivo using an endomicroscope. Then enhanced green fluorescent protein (eGFP)-labeled MSC was tracked in vivo, and acquired images were compared with immunofluorescence, immunohistology, and fluorescent in situ hybridization results.
Results:
Endomicroscopy visualized clearly the eGFP-labeled or carboxyfluorescein succinimidyl ester-stained MSC ex vivo. Endomicroscopy using the FIVE1 system could track eGFP-labeled MSC with distinct in vivo features. Immunofluorescence, immunohistochemistry, and fluorescent in situ hybridization confirmed the presence of eGFP-positive cells. In vivo endomicroscopy could quantify the transplanted MSCs that homed to colonic mucosa of the recipient rat in multiple models, including the rat-to-rat allograft, human-to-rat xenograft, hypoxia-induced MSC, and busulfan immunosuppressed recipient rat models. After hypoxia induction, there was a trend of enhanced rat MSC homing to the inflamed mucosa as visualized by endomicroscopy (114.1 in hypoxia group versus 34.3 in other 3 groups combined, t = 2.14, P = 0.0644).
Conclusions:
Endomicroscopy is a novel and promising tool to track transplanted MSCs to the colonic mucosa. This clinical available noninvasive cellular tracking method may provide new insight to individualize each recipient's regimen in the future.
Insights
Endomicroscopy noninvasively tracks mesenchymal stem cells (MSCs) in vivo, offering a new method to document MSCs in the colon. This technique aids in personalizing inflammatory bowel disease treatments.
Area of Science:
- Gastroenterology
- Cell Biology
- Medical Imaging
Background:
- Mesenchymal stem cells (MSCs) show promise for treating inflammatory bowel disease (IBD).
- Current methods to track MSCs in the intestinal mucosa are limited.
- Noninvasive in vivo tracking of MSCs is needed for clinical applications.
Purpose of the Study:
- To evaluate endomicroscopy as a tool for noninvasively tracking mesenchymal stem cells (MSCs) in the colonic mucosa in vivo.
- To compare endomicroscopy findings with established histological methods for cell detection.
Main Methods:
- Rat MSCs were fluorescently labeled and imaged ex vivo and in vivo using an endomicroscope (FIVE1 system).
- In vivo tracking of enhanced green fluorescent protein (eGFP)-labeled MSCs was performed.
- Results were validated using immunofluorescence, immunohistochemistry, and fluorescent in situ hybridization.
Main Results:
- Endomicroscopy clearly visualized labeled MSCs ex vivo and tracked eGFP-labeled MSCs in vivo.
- The technique successfully quantified transplanted MSCs homing to the colonic mucosa in various rat models (allograft, xenograft, hypoxia, immunosuppression).
- A trend of enhanced MSC homing to inflamed mucosa post-hypoxia was observed.
Conclusions:
- Endomicroscopy is a novel, noninvasive tool for tracking transplanted MSCs in the colonic mucosa.
- This clinical-available method provides cellular resolution for in vivo tracking.
- It holds potential for personalizing treatment regimens for IBD patients.
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