Spatio-Temporal Metabolokinetics and Efficacy of Human Placenta-Derived Mesenchymal Stem/Stromal Cells on Mice with Refr
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Spatio-Temporal Metabolokinetics and Efficacy of Human Placenta-Derived Mesenchymal Stem/Stromal Cells on Mice with Refractory Crohn’s-like Enterocutaneous Fistula Huixing Hou 1 & Leisheng Zhang 2,3,4 Xiaocang Cao 1
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Liyun Duan 1
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Yuanyuan Liu 1 & Zhongchao Han 3,4 & Zongjin Li 2
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Accepted: 29 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Crohn’s disease (CD) with externally fistulizing openings indicates the aggressive and relapsing manifestation and results in undesirable long-term outcomes of patients. MSC-based approach combined with multidisciplinary strategy has mandated a redefinition of the administration and management of numerous recurrent and refractory diseases whereas the spatio-temporal evaluation of the metabolokinetics and efficacy of MSCs on intractable CD with enterocutaneous fistula (EF) are largely inaccessible and dauntingly complex. Herein, we primitively established dual-fluorescence expressing placenta-derived MSCs (DF-MSCs) and explored their multidimensional attributes, including cytomorphology, immunophenotying, multilineage differentiation and long-term proliferation, together with the recognition of bifluorescence intensity (BLI). Then, with the aid of in vivo living imaging, clinicopathological or inflammatory cytokine examinations and in vitro analyses, we systematically and meticulously dissected the metabolokinetics and curative effect of MSCs on mice with refractory Crohn’s-like EF (EF mice), together with revealing the underlying mechanism including reactive oxygen species (ROS) and neovascularization. Strikingly, the DF-MSCs exhibited stabilized BLI and biological properties. The spatio-temporal distribution and therapeutic process of MSCs in EF mice were intuitively delineated. Meanwhile, our data indicated the curative mechanisms of DF-MSCs by simultaneously downregulating ROS and accelerating neovascularization. Collectively, we systematically illuminated the spatiotemporal biofunction and mechanism of DF-MSCs on EF mice. Our findings have supplied new references for safety and effectiveness assessments as well as the establishment of guidelines for optimal administrations of MSC-based cytotherapy in preclinical studies, which collectively indicates the prospect of P-MSC administration in clinical trials during a wide spectrum of disease remodeling including the fistulizing CD.
Huixing Hou and Leisheng Zhang contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12015-020-10053-2) contains supplementary material, which is available to authorized users. * Leisheng Zhang [email protected]
1302-1; https://stemcellres.biomedcentral.com/articles/10.1186/ s13287-018-0888-z; https://www.thno.org/v08p5348.htm
* Zongjin Li [email protected]
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* Xiaocang Cao [email protected]; https://www.thno.org/v08p5348.htm
Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin 300052, China
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