Human umbilical cord mesenchymal stem cells improve bone marrow hematopoiesis through regulation of bone marrow adipose tissue.

IF 3.5 2区 生物学 Q3 CELL BIOLOGY
Jingyi Feng, Miao Zhang, Huanying Ren, Yan Ren, Zhuanghui Hao, Sicheng Bian, Jiangxia Cui, Shuo Li, Jing Xu, Muteb Muyey Daniel, Fanggang Ren, Zhifang Xu, Yanhong Tan, Xiuhua Chen, Yaofang Zhang, Jianmei Chang, Hongwei Wang
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Abstract

Bone marrow adipose tissue (BMAT) exhibits a multitude of biological functionalities and influences hematopoiesis. The adiposity status of the bone marrow may play a role in the decline of hematopoietic function. Mesenchymal stem cells (MSCs) constitute crucial regulators within the bone marrow microenvironment; however, their precise role in modulating BMAT and the subsequent implications for hematopoiesis remain poorly understood. We conducted in vivo studies to observe the effects of human umbilical cord mesenchymal stem cells (hucMSCs) on BMAT accumulation and restoration of hematopoietic function in mice with drug-induced hematopoietic impairment. Concurrently, in vitro co-culture experiments were used to investigate the impact of hucMSCs on preadipocytes and mature adipocytes, and the potential subsequent consequences for hematopoietic cells. Moreover, we explored the potential mechanisms underlying these interactions. Our findings reveal that hucMSCs concomitantly mitigate BMAT accumulation and facilitate the recovery of hematopoietic function in mouse models with drug-induced hematopoietic impairment. In vitro, hucMSCs potentially impede adipogenic differentiation of 3T3-L1 preadipocytes through interference with the JAK2/STAT3 signaling pathway and affect the functionality of mature adipocytes, thus mitigating the detrimental effects of adipocytes on hematopoietic stem cells (HSCs). Furthermore, we demonstrate that hucMSCs may protect hematopoietic cells from adipocyte-induced damage by protecting antioxidative mechanisms. These results suggest that hucMSCs exhibit an inhibitory effect on the excessive expansion of adipose tissue and modulate adipose tissue function, which may potentially contribute to the regulation of the bone marrow microenvironment and favorably influence hematopoietic function improvement.

人脐带间充质干细胞通过调节骨髓脂肪组织改善骨髓造血功能。
骨髓脂肪组织(BMAT)表现出多种生物学功能并影响造血。骨髓的肥胖状态可能在造血功能下降中起作用。间充质干细胞(MSCs)是骨髓微环境中至关重要的调节因子;然而,它们在调节BMAT中的确切作用以及随后对造血的影响仍然知之甚少。我们在体内研究了人脐带间充质干细胞(hucMSCs)对药物性造血损伤小鼠BMAT积累和造血功能恢复的影响。同时,体外共培养实验研究了hucMSCs对前脂肪细胞和成熟脂肪细胞的影响,以及对造血细胞的潜在后续影响。此外,我们还探讨了这些相互作用的潜在机制。我们的研究结果表明,在药物诱导的造血功能损伤小鼠模型中,hucMSCs可以同时减轻BMAT的积累并促进造血功能的恢复。在体外,hucMSCs可能通过干扰JAK2/STAT3信号通路阻碍3T3-L1前脂肪细胞的成脂分化,影响成熟脂肪细胞的功能,从而减轻脂肪细胞对造血干细胞(hsc)的有害影响。此外,我们证明了humscs可能通过保护抗氧化机制来保护造血细胞免受脂肪细胞诱导的损伤。这些结果表明,hucMSCs具有抑制脂肪组织过度扩张和调节脂肪组织功能的作用,这可能有助于调节骨髓微环境并对造血功能的改善产生有利影响。
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来源期刊
Molecular and Cellular Biochemistry
Molecular and Cellular Biochemistry 生物-细胞生物学
CiteScore
8.30
自引率
2.30%
发文量
293
审稿时长
1.7 months
期刊介绍: Molecular and Cellular Biochemistry: An International Journal for Chemical Biology in Health and Disease publishes original research papers and short communications in all areas of the biochemical sciences, emphasizing novel findings relevant to the biochemical basis of cellular function and disease processes, as well as the mechanics of action of hormones and chemical agents. Coverage includes membrane transport, receptor mechanism, immune response, secretory processes, and cytoskeletal function, as well as biochemical structure-function relationships in the cell. In addition to the reports of original research, the journal publishes state of the art reviews. Specific subjects covered by Molecular and Cellular Biochemistry include cellular metabolism, cellular pathophysiology, enzymology, ion transport, lipid biochemistry, membrane biochemistry, molecular biology, nuclear structure and function, and protein chemistry.
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