Hydrogel microspheres for spatiotemporally controlled delivery of RNA and silencing gene expression within scaffold-free tissue engineered constructs.
Hydrogel microspheres for spatiotemporally controlled delivery of RNA and silencing gene expression within scaffold-free tissue engineered constructs.
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DOI：
10.1016/j.actbio.2021.01.013
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发表时间：
2021-04-01
影响因子：
9.7
通讯作者：
Alsberg E
中科院分区：
文献类型：
--
作者：
McMillan A;Nguyen MK;Huynh CT;Sarett SM;Ge P;Chetverikova M;Nguyen K;Grosh D;Duvall CL;Alsberg E
用于RNA干扰（RNAi）分子（包括小干扰（siRNA）和微小RNA（miRNA））的受控释放的递送系统具有指导干细胞分化用于再生肌肉骨骼应用的潜力。到目前为止，在这一领域的本地化RNA递送平台主要集中在基于散装支架的方法，这可能会干扰细胞-细胞相互作用，这对于重现组织再生策略中的一些天然肌肉骨骼发育和愈合过程至关重要。相比之下，无支架、高密度的人间充质干细胞（hMSC）聚集体可能提供一种创造更仿生微环境的途径。在此，通过水乳液方法制备包封siRNA胶束的可光交联葡聚糖微球（MS），并将其掺入hMSC聚集体中用于生物活性siRNA的局部和持续递送。siRNA胶束在28天的过程中以持续的方式从MS释放，并且释放的siRNA保留了其抑制细胞基因沉默的能力。在hMSC聚集体内掺入荧光标记的siRNA（siGLO）负载的MS表现出可调的siGLO递送和干细胞摄取。将载有靶向绿色荧光蛋白（siGFP）的siRNA的MS并入GFP-hMSC聚集体内提供了siGFP在构建体内的持续呈递，并延长了GFP沉默长达15天。该平台系统能够在干细胞聚集体内持续基因沉默，因此在组织再生应用中显示出巨大的潜力。
Delivery systems for controlled release of RNA interference (RNAi) molecules, including small interfering (siRNA) and microRNA (miRNA), have the potential to direct stem cell differentiation for regenerative musculoskeletal applications. To date, localized RNA delivery platforms in this area have focused predominantly on bulk scaffold-based approaches, which can interfere with cell-cell interactions important for recapitulating some native musculoskeletal developmental and healing processes in tissue regeneration strategies. In contrast, scaffold-free, high density human mesenchymal stem cell (hMSC) aggregates may provide an avenue for creating a more biomimetic microenvironment. Here, photocrosslinkable dextran microspheres (MS) encapsulating siRNA-micelles were prepared via an aqueous emulsion method and incorporated within hMSC aggregates for localized and sustained delivery of bioactive siRNA. siRNA-micelles released from MS in a sustained fashion over the course of 28 days, and the released siRNA retained its ability to transfect cells for gene silencing. Incorporation of fluorescently labeled siRNA (siGLO)-laden MS within hMSC aggregates exhibited tunable siGLO delivery and uptake by stem cells. Incorporation of MS loaded with siRNA targeting green fluorescent protein (siGFP) within GFP-hMSC aggregates provided sustained presentation of siGFP within the constructs and prolonged GFP silencing for up to 15 days. This platform system enables sustained gene silencing within stem cell aggregates and thus shows great potential in tissue regeneration applications.
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DOI：
10.1088/1748-6041/7/2/024108
发表时间：
2012-04
期刊：
Biomedical materials (Bristol, England)
影响因子：
--
作者：
Desai ES;Tang MY;Ross AE;Gemeinhart RA
通讯作者：
Gemeinhart RA
影响因子：
14.9
作者：
Bartlett DW;Davis ME
通讯作者：
Davis ME
表面纳米技术与内吞作用之间的新兴联系：对非病毒基因递送的影响。
影响因子：
17.4
作者：
Adler AF;Leong KW
通讯作者：
Leong KW
影响因子：
16.1
作者：
Beavers, Kelsey R.;Nelson, Christopher E.;Duvall, Craig L.
通讯作者：
Duvall, Craig L.
DOI：
10.1016/j.jconrel.2008.10.004
发表时间：
2009-02-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Convertine AJ;Benoit DS;Duvall CL;Hoffman AS;Stayton PS
通讯作者：
Stayton PS