PDF(Pubmed)
Abstract：
BACKGROUND: Adipose-derived stem cells (ASCs) represent the most advantageous choice for soft tissue regeneration. Studies proved the recruitment of ASCs post tissue injury was mediated by chemokine CXCL12, but the mechanism by which CXCL12 is generated after tissue injury remains unclear. Migrasomes are newly discovered membrane-bound organelles that could deliver CXCL12 spatially and temporally in vivo. In this study, we sought to investigate whether migrasomes participate ASC-mediated tissue regeneration.
METHODS: Discrepant and asymmetrical soft tissue regeneration mice model were established, in which HE staining, immunofluorescent staining, western blot and qPCR were conducted to confirm the role of CXCL12 and migrasomes in ASC-mediated tissue regeneration. Characterization of ASC-derived migrasomes were carried out by confocal microscopy, scanning electron microscopy, transmission electron microscopy as well as western blot analysis. The function and mechanism of migrasomes were further testified by assisting tissue regeneration with isolated migrasomes in vivo and by in vitro transwell combined with co-culture system.
RESULTS: Here, we show for the first time that migrasomes participate in soft tissue regeneration. ASCs generate migrasomes enriched with CXCL12 to mediate tissue regeneration. Migrasomes from ASCs could promote stem cells migration by activating CXCR4/RhoA signaling in vivo and in vitro. Chemoattracted ASCs facilitate regeneration, as demonstrated by the upregulation of an adipogenesis-associated protein. This positive feed-back-loop creates a favorable microenvironment for soft tissue regeneration. Thus, migrasomes represent a new therapeutic target for ASC-mediated tissue regeneration.
CONCLUSIONS: Our findings reveal a previously unknown function of ASCs in mediating tissue regeneration by generating migrasomes. The ASC-derived migrasomes can restore tissue regeneration by recruiting stem cells, which highlighting the potential application of ASC-derived migrasomes in regenerative medicine.
METHODS: Discrepant and asymmetrical soft tissue regeneration mice model were established, in which HE staining, immunofluorescent staining, western blot and qPCR were conducted to confirm the role of CXCL12 and migrasomes in ASC-mediated tissue regeneration. Characterization of ASC-derived migrasomes were carried out by confocal microscopy, scanning electron microscopy, transmission electron microscopy as well as western blot analysis. The function and mechanism of migrasomes were further testified by assisting tissue regeneration with isolated migrasomes in vivo and by in vitro transwell combined with co-culture system.
RESULTS: Here, we show for the first time that migrasomes participate in soft tissue regeneration. ASCs generate migrasomes enriched with CXCL12 to mediate tissue regeneration. Migrasomes from ASCs could promote stem cells migration by activating CXCR4/RhoA signaling in vivo and in vitro. Chemoattracted ASCs facilitate regeneration, as demonstrated by the upregulation of an adipogenesis-associated protein. This positive feed-back-loop creates a favorable microenvironment for soft tissue regeneration. Thus, migrasomes represent a new therapeutic target for ASC-mediated tissue regeneration.
CONCLUSIONS: Our findings reveal a previously unknown function of ASCs in mediating tissue regeneration by generating migrasomes. The ASC-derived migrasomes can restore tissue regeneration by recruiting stem cells, which highlighting the potential application of ASC-derived migrasomes in regenerative medicine.
摘要：
背景:脂肪来源的干细胞(ASC)代表软组织再生的最有利选择。研究证明组织损伤后ASCs的募集是由趋化因子CXCL12介导的，但组织损伤后CXCL12产生的机制尚不清楚。迁移体是新发现的膜结合细胞器，可以在体内空间和时间上传递CXCL12。在这项研究中,我们试图研究迁移体是否参与ASC介导的组织再生.
方法：建立差异和不对称软组织再生小鼠模型，其中HE染色，免疫荧光染色，进行蛋白质印迹和qPCR以证实CXCL12和迁移体在ASC介导的组织再生中的作用。通过共聚焦显微镜对ASC衍生的迁移体进行表征，扫描电子显微镜，透射电子显微镜以及蛋白质印迹分析。通过体内分离的迁移体辅助组织再生以及体外transpell结合共培养系统进一步证明了迁移体的功能和机制。
结果：这里，我们首次显示迁移体参与软组织再生。ASC产生富含CXCL12的迁移体以介导组织再生。来自ASC的迁移体可以通过激活体内和体外的CXCR4/RhoA信号来促进干细胞迁移。化学吸引的ASCs促进再生，正如脂肪生成相关蛋白的上调所证明的。这种正反馈回路为软组织再生创造了有利的微环境。因此，迁移体代表了ASC介导的组织再生的新治疗靶点。
结论：我们的发现揭示了ASCs在通过产生迁移体来介导组织再生中的一种以前未知的功能。ASC衍生的迁移体可以通过招募干细胞来恢复组织再生，这突出了ASC衍生的迁移体在再生医学中的潜在应用。
方法：建立差异和不对称软组织再生小鼠模型，其中HE染色，免疫荧光染色，进行蛋白质印迹和qPCR以证实CXCL12和迁移体在ASC介导的组织再生中的作用。通过共聚焦显微镜对ASC衍生的迁移体进行表征，扫描电子显微镜，透射电子显微镜以及蛋白质印迹分析。通过体内分离的迁移体辅助组织再生以及体外transpell结合共培养系统进一步证明了迁移体的功能和机制。
结果：这里，我们首次显示迁移体参与软组织再生。ASC产生富含CXCL12的迁移体以介导组织再生。来自ASC的迁移体可以通过激活体内和体外的CXCR4/RhoA信号来促进干细胞迁移。化学吸引的ASCs促进再生，正如脂肪生成相关蛋白的上调所证明的。这种正反馈回路为软组织再生创造了有利的微环境。因此，迁移体代表了ASC介导的组织再生的新治疗靶点。
结论：我们的发现揭示了ASCs在通过产生迁移体来介导组织再生中的一种以前未知的功能。ASC衍生的迁移体可以通过招募干细胞来恢复组织再生，这突出了ASC衍生的迁移体在再生医学中的潜在应用。
