Evaluating the defect targeting effects and osteogenesis promoting capacity of exosomes from 2D- and 3D-cultured human adipose-derived stem cells
Evaluating the defect targeting effects and osteogenesis promoting capacity of exosomes from 2D- and 3D-cultured human adipose-derived stem cells
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DOI：
10.1016/j.nantod.2023.101789
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发表时间：
2023-04
期刊：
影响因子：
17.4
通讯作者：
R. Chen;Taojin Feng;Shi Cheng;Ming Chen;Yi Li;Zihui Yu;Ziying Xu;Pengbin Yin;Licheng Zhang-Li
中科院分区：
文献类型：
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作者：
R. Chen;Taojin Feng;Shi Cheng;Ming Chen;Yi Li;Zihui Yu;Ziying Xu;Pengbin Yin;Licheng Zhang-Li
干细胞来源的外切体在骨缺损修复中显示出巨大的治疗潜力。系统地给药外切体是一种微创给药方法；然而，缺乏对病变靶向能力和修复促进效果的评估。在本研究中，将人脂肪干细胞(HADSCs)产生的外切体静脉注射到颅骨缺陷小鼠体内。发现外切体优先聚集在骨组织中，尤其是在颅骨缺损处。此外，根据病变部位更多的新骨形成表明，外切体治疗促进了成骨。此外，三维(3D)培养对hADSCs的影响通过转录组测序进行评估，在3D培养的hADSCs中，骨发育、软骨发育等几条途径被上调，表明组织修复能力得到改善。此外，与2D培养的hADSCs相比，3D培养的hADSCs的外切体显示出明显更好的骨靶向作用和骨修复能力。总而言之，这项研究强调了hADSCs来源的外切体的骨靶向和促成骨作用，这一点可以通过3D培养亲本细胞来进一步增强。全身注射干细胞来源的外切体可以作为一种简单和微创的方法来促进骨缺损的修复。
Exosomes derived from stem cells show great therapeutic potential in bone defect repair. Systemic administration of exosomes represents as a minimally invasive delivery approach; however, evaluation for the lesion-targeting capacity and repair promotion efficacy lacks. In this study, exosomes produced by human adipose-derived stem cells (hADSCs) are intravenously injected to calvarial defect mice. It is found that exosomes preferentially accumulate at bone and especially at the calvarial defect site. In addition, exosomes treatment promotes osteogenesis as indicated by more newly formed bone at the lesion site. Furthermore, the impact of three-dimensional (3D) culture on hADSCs is evaluated by transcriptome sequencing and several pathways such as bone development, cartilage development are up-regulated in 3D-cultured hADSCs, suggesting an improved tissue repair capacity. Moreover, exosomes from 3D-cultured hADSCs show distinctly superior bone-targeting effects and bone repair capacity, as compared to those derived from 2D-cultured hADSCs. Collectively, this study highlights the bone-targeting and pro-osteogenic effects of hADSCs-derived exosomes, which could be further enhanced by 3D culture of the parental cells. Systemic injection of stem cell-derived exosomes could serve as a simple and minimally invasive approach to facilitate bone defect repair.