Abstract:
:Chemokines are guiding cues for directional trafficking of mesenchymal stem cells (MSC) upon injury and local chemokine delivery at injury sites is an up-to-date strategy to potentiate and prolong recruitment of MSC. In this study we present the chemokine CCL25, also referred to as thymus-expressed chemokine, to mobilize human MSC along positive but not along negative gradients. We hence proceeded to design a biodegradable and injectable release device for CCL25 on the basis of poly(lactic-co-glycolic acid) (PLGA). The conducted studies had the objective to optimize PLGA microparticle fabrication by varying selected formulation parameters, such as polymer type, microparticle size and interior phase composition. We found that microparticles of DV,50∼75 µm and fabricated using end-capped polymers, BSA as carrier protein and vortex mixing to produce the primary emulsion yielded high chemokine loading and delayed CCL25 release. To determine bioactivity, we investigated CCL25 released during the microparticle erosion phase and showed that deacidification of the release medium was required to induce significant MSC mobilization. The designed PLGA microparticles represent an effective and convenient off-the-shelf delivery tool for the delayed release of CCL25. However, continuative in vivo proof-of-concept studies are required to demonstrate enhanced recruitment of MSC and/or therapeutical effects in response to CCL25 release microparticles. STATEMENT OF SIGNIFICANCE:With the discovery of chemokines, particularly CXCL12, as stimulators of stem cell migration, the development of devices that release CXCL12 has proceeded quickly in the last few years. In this manuscript we introduce CCL25 as chemokine to induce mobilization of human MSC. This study proceeds to demonstrate how selection of key formulation parameters of CCL25 loading into PLGA microparticles exerts considerable influence on CCL25 release. This is important for a broad range of efforts in in situ tissue engineering where the candidate chemokine and the delivery device need to be selected carefully. The use of such a cell-free CCL25 release device may provide a new therapeutic option in regenerative medicine.
journal_name
Acta Biomaterjournal_title
Acta biomaterialiaauthors
Fröhlich K,Hartzke D,Schmidt F,Eucker J,Gurlo A,Sittinger M,Ringe Jdoi
10.1016/j.actbio.2018.01.036subject
Has Abstractpub_date
2018-03-15 00:00:00pages
290-300eissn
1742-7061issn
1878-7568pii
S1742-7061(18)30047-3journal_volume
69pub_type
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journal_title:Acta biomaterialia
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journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2009.04.005
更新日期:2009-10-01 00:00:00
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journal_title:Acta biomaterialia
pub_type: 杂志文章,评审
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pub_type: 杂志文章
doi:10.1016/j.actbio.2010.12.016
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journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2009.05.011
更新日期:2009-10-01 00:00:00
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journal_title:Acta biomaterialia
pub_type: 杂志文章
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journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2006.06.005
更新日期:2006-11-01 00:00:00
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journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2016.01.035
更新日期:2016-03-01 00:00:00
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doi:10.1016/j.actbio.2016.03.035
更新日期:2016-08-01 00:00:00
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journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2008.03.017
更新日期:2008-09-01 00:00:00
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journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2016.08.038
更新日期:2016-10-15 00:00:00
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journal_title:Acta biomaterialia
pub_type: 杂志文章
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更新日期:2016-11-01 00:00:00
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journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2010.11.034
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journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2009.08.005
更新日期:2010-02-01 00:00:00
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journal_title:Acta biomaterialia
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doi:10.1016/j.actbio.2010.03.003
更新日期:2010-08-01 00:00:00
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journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2020.08.031
更新日期:2020-10-01 00:00:00
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journal_title:Acta biomaterialia
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journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2014.02.041
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journal_title:Acta biomaterialia
pub_type: 杂志文章
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