Abstract:
BACKGROUND:Mesenchymal stromal/stem cells (MSCs) have demonstrated pro-healing properties due to their anti-inflammatory, angiogenic, and even antibacterial properties. We have shown previously that minocycline enhances the wound healing phenotype of MSCs, and MSCs encapsulated in poly(ethylene glycol) and gelatin-based hydrogels with minocycline have antibacterial properties against Staphylococcus aureus (SA). Here, we investigated the signaling pathway that minocycline modulates in MSCs which results in their enhanced wound healing phenotype and determined whether preconditioning MSCs with minocycline has an effect on antimicrobial activity. We further investigated the in-vivo antimicrobial efficacy of MSC and antibiotic-loaded hydrogels in inoculated full-thickness cutaneous wounds. METHODS:Modulation of cell signaling pathways in MSCs with minocycline was analyzed via western blot, immunofluorescence, and ELISA. Antimicrobial efficacy of MSCs pretreated with minocycline was determined by direct and transwell coculture with SA. MSC viability after SA coculture was determined via a LIVE/DEAD® stain. Internalization of SA by MSCs pretreated with minocycline was determined via confocal imaging. All protein and cytokine analysis was done via ELISA. The in-vivo antimicrobial efficacy of MSC and antibiotic-loaded hydrogels was determined in Sprague-Dawley rats inoculated with SA. Two-way ANOVA for multiple comparisons was used with Bonferroni test assessment and an unpaired two-tailed Student's t test was used to determine p values for all assays with multiple or two conditions, respectively. RESULTS:Minocycline leads to the phosphorylation of transcriptional nuclear factor-κB (NFκB), but not c-Jun NH2-terminal kinase (JNK) or mitogen-activated protein kinase (ERK). Inhibition of NFκB activation prevented the minocycline-induced increase in VEGF secretion. Preconditioning of MSCs with minocycline led to a reduced production of the antimicrobial peptide LL-37, but enhanced antimicrobial activity against SA via an increased production of IL-6 and SA internalization. MSC and antibiotic-loaded hydrogels reduced SA bioburden in inoculated wounds over 3 days and accelerated reepithelialization. CONCLUSIONS:Minocycline modulates the NFκB pathway in MSCs that leads to an enhanced production of IL-6 and internalization of SA. This mechanism may have contributed to the in-vivo antibacterial efficacy of MSC and antibiotic-loaded hydrogels.
journal_name
Stem Cell Res Therjournal_title
Stem cell research & therapyauthors
Guerra AD,Rose WE,Hematti P,Kao WJdoi
10.1186/s13287-017-0623-1subject
Has Abstractpub_date
2017-07-21 00:00:00pages
171issue
1issn
1757-6512pii
10.1186/s13287-017-0623-1journal_volume
8pub_type
杂志文章abstract:INTRODUCTION:Administration of bone marrow-derived cells produces beneficial effects in experimental extrapulmonary acute respiratory distress syndrome (ARDS). However, there are controversies regarding the effects of timing of cell administration and initial insult severity on inflammatory response. We evaluated the e...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/scrt334
更新日期:2013-10-13 00:00:00
abstract:INTRODUCTION:Fallopian tube, which is normally discarded in surgical procedures, has proven to be a source of mesenchymal stem cells (MSCs) with increasing evidence. However, fallopian tube mucosa, which can be acquired via non-invasive procedures, is a previously unknown source of MSCs. In the present study, we explor...
journal_title:Stem cell research & therapy
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journal_title:Stem cell research & therapy
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journal_title:Stem cell research & therapy
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journal_title:Stem cell research & therapy
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journal_title:Stem cell research & therapy
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journal_title:Stem cell research & therapy
pub_type: 杂志文章,评审
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journal_title:Stem cell research & therapy
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journal_title:Stem cell research & therapy
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journal_title:Stem cell research & therapy
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journal_title:Stem cell research & therapy
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journal_title:Stem cell research & therapy
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journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-020-01888-0
更新日期:2020-09-07 00:00:00
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journal_title:Stem cell research & therapy
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更新日期:2012-03-19 00:00:00
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journal_title:Stem cell research & therapy
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pub_type: 杂志文章,随机对照试验
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更新日期:2017-06-24 00:00:00
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journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-019-1190-4
更新日期:2019-03-12 00:00:00
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journal_title:Stem cell research & therapy
pub_type: 杂志文章
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journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-018-0945-7
更新日期:2018-07-18 00:00:00
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journal_title:Stem cell research & therapy
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journal_title:Stem cell research & therapy
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更新日期:2019-10-17 00:00:00
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journal_title:Stem cell research & therapy
pub_type: 杂志文章
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更新日期:2020-07-16 00:00:00
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journal_title:Stem cell research & therapy
pub_type: 杂志文章
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更新日期:2013-05-21 00:00:00
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journal_title:Stem cell research & therapy
pub_type: 临床试验,杂志文章
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更新日期:2017-08-01 00:00:00
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journal_title:Stem cell research & therapy
pub_type: 已发布勘误
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更新日期:2020-01-23 00:00:00
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journal_title:Stem cell research & therapy
pub_type: 杂志文章
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更新日期:2021-01-07 00:00:00
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journal_title:Stem cell research & therapy
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journal_title:Stem cell research & therapy
pub_type: 杂志文章
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