Dataset Information

Exogenous L-arginine increases intestinal stem cell function through CD90+ stromal cells producing mTORC1-induced Wnt2b.

ABSTRACT: The renewal and repair of intestinal epithelium depend on the self-renewal of intestinal stem cells (ISCs) under physiological and pathological conditions. Although previous work has established that exogenous nutrients regulate adult stem cell activity, little is known about the regulatory effect of L-arginine on ISCs. In this study we utilize mice and small intestinal (SI) organoid models to clarify the role of L-arginine on epithelial differentiation of ISCs. We show that L-arginine increases expansion of ISCs in mice. Furthermore, CD90⁺ intestinal stromal cells augment stem-cell function in response to L-arginine in co-culture experiments. Mechanistically, we find that L-arginine stimulates Wnt2b secretion by CD90⁺ stromal cells through the mammalian target of rapamycin complex 1 (mTORC1) and that blocking Wnt2b production prevents L-arginine-induced ISC expansion. Finally, we show that L-arginine treatment protects the gut in response to injury. Our findings highlight an important role for CD90+ stromal cells in L-arginine-stimulated ISC expansion.

SUBMITTER: Hou Q

PROVIDER: S-EPMC7584578 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Exogenous L-arginine increases intestinal stem cell function through CD90+ stromal cells producing mTORC1-induced Wnt2b.

Hou Qihang Q Dong Yuanyang Y Huang Jingxi J Liao Chaoyong C Lei Jiaqi J Wang Youli Y Lai Yujiao Y Bian Yifei Y He Yang Y Sun Jingjing J Sun Meng M Jiang Qiuyu Q Wang Bo B Yu Zhengquan Z Guo Yuming Y Zhang Bingkun B

Communications biology 20201023 1

The renewal and repair of intestinal epithelium depend on the self-renewal of intestinal stem cells (ISCs) under physiological and pathological conditions. Although previous work has established that exogenous nutrients regulate adult stem cell activity, little is known about the regulatory effect of L-arginine on ISCs. In this study we utilize mice and small intestinal (SI) organoid models to clarify the role of L-arginine on epithelial differentiation of ISCs. We show that L-arginine increases ...[more]

PMID: 33097830

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Project description:Mesenchymal stromal cells (MSCs) are an attractive option for cell therapy for type 1 diabetes mellitus (DM). These cells can be obtained from many sources, but bone marrow and adipose tissue are the most studied. MSCs have distinct advantages since they are nonteratogenic, nonimmunogenic and have immunomodulatory functions. Insulin-producing cells (IPCs) can be generated from MSCs by gene transfection, gene editing or directed differentiation. For directed differentiation, MSCs are usually cultured in a glucose-rich medium with various growth and activation factors. The resulting IPCs can control chemically-induced diabetes in immune-deficient mice. These findings are comparable to those obtained from pluripotent cells. PD-L1 and PD-L2 expression by MSCs is upregulated under inflammatory conditions. Immunomodulation occurs due to the interaction between these ligands and PD-1 receptors on T lymphocytes. If this function is maintained after differentiation, life-long immunosuppression or encapsulation could be avoided. In the clinical setting, two sites can be used for transplantation of IPCs: the subcutaneous tissue and the omentum. A 2-stage procedure is required for the former and a laparoscopic procedure for the latter. For either site, cells should be transplanted within a scaffold, preferably one from fibrin. Several questions remain unanswered. Will the transplanted cells be affected by the antibodies involved in the pathogenesis of type 1 DM? What is the functional longevity of these cells following their transplantation? These issues have to be addressed before clinical translation is attempted. Graphical Abstract Bone marrow MSCs are isolated from the long bone of SD rats. Then they are expanded and through directed differentiation insulin-producing cells are formed. The differentiated cells are loaded onto a collagen scaffold. If one-stage transplantation is planned, a drug delivery system must be incorporated to ensure immediate oxygenation, promote vascularization and provide some growth factors. Some mechanisms involved in the immunomodulatory function of MSCs. These are implemented either by cell to cell contact or by the release of soluble factors. Collectively, these pathways results in an increase in T-regulatory cells.

Dataset Information

Exogenous L-arginine increases intestinal stem cell function through CD90+ stromal cells producing mTORC1-induced Wnt2b.

Publications

Exogenous L-arginine increases intestinal stem cell function through CD90+ stromal cells producing mTORC1-induced Wnt2b.

Similar Datasets

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