Potential of mesenchymal stem cell in stabilization of abdominal aortic aneurysm sac

Moral, Luis Riera del; Largo, Carlota; Ramirez, Jairo; Clemente, Luz Vega; Heredero, Álvaro Fernández; Cubas, L. Riera de; García-Olmo, Damián; García‐Arranz, Mariano

doi:10.1016/j.jss.2014.12.020

Cited by 10 publications

(6 citation statements)

References 22 publications

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“…Georgiev-Hristov et al[ 27 ] showed an early switch from acute to chronic inflammation in the presence of ASCs after tracheal anastomosis. And, Riera del Moral et al[ 66 ] observed less acute and chronic inflammation and increasing fibrosis of aneurysm sacs in pigs.…”

Section: Discussionmentioning

confidence: 99%

Rat model of anal sphincter injury and two approaches for stem cell administration

Trébol¹,

Georgiev-Hristov²,

Vega-Clemente³

et al. 2018

WJSC

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AIMTo establish a rat model of anal sphincter injury and test different systems to provide stem cells to injured area.METHODSAdipose-derived stem cells (ASCs) were isolated from BDIX rats and were transfected with green fluorescent protein (GFP) for cell tracking. Biosutures (sutures covered with ASCs) were prepared with 1.5 x 106 GFP-ASCs, and solutions of 106 GFP-ASCs in normal saline were prepared for injection. Anorectal normal anatomy was studied on Wistar and BDIX female rats. Then, we designed an anal sphincter injury model consisting of a 1-cm extra-mucosal miotomy beginning at the anal verge in the anterior middle line. The sphincter lesion was confirmed with conventional histology (hematoxylin and eosin) and immunofluorescence with 4', 6-diamidino-2-phenylindole (commonly known as DAPI), GFP and α-actin. Functional effect was assessed with basal anal manometry, prior to and after injury. After sphincter damage, 36 BDIX rats were randomized to three groups for: (1) Cell injection without repair; (2) biosuture repair; and (3) conventional suture repair and cell injection. Functional and safety studies were conducted on all the animals. Rats were sacrificed after 1, 4 or 7 d. Then, histological and immunofluorescence studies were performed on the surgical area.RESULTSWith the described protocol, biosutures had been covered with at least 820000-860000 ASCs, with 100% viability. Our studies demonstrated that some ASCs remained adhered after suture passage through the muscle. Morphological assessment showed that the rat anal anatomy is comparable with human anatomy; two sphincters are present, but the external sphincter is poorly developed. Anal sphincter pressure data showed spontaneous, consistent, rhythmic anal contractions, taking the form of “plateaus” with multiple twitches (peaks) in each pressure wave. These basal contractions were very heterogeneous; their frequency was 0.91-4.17 per min (mean 1.6980, SD 0.57698), their mean duration was 26.67 s and mean number of peaks was 12.53. Our morphological assessment revealed that with the aforementioned surgical procedure, both sphincters were completely sectioned. In manometry, the described activity disappeared and was replaced by a gentle oscillation of basal line, without a recognizable pattern. Surprisingly, these findings appeared irrespective of injury repair or not. ASCs survived in this potentially septic area for 7 d, at least. We were able to identify them in 84% of animals, mainly in the muscular section area or in the tissue between the muscular endings. ASCs formed a kind of “conglomerate” in rats treated with injections, while in the biosuture group, they wrapped the suture. ASCs were also able to migrate to the damaged zone. No relevant adverse events or mortality could be related to the stem cells in our study. We also did not find unexpected tissue growths.CONCLUSIONThe proposed procedure produces a consistent sphincter lesion. Biosutures and injections are suitable for cell delivery. ASCs survive and are completely safe in this clinical s...

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Section: Discussionmentioning

confidence: 99%

Rat model of anal sphincter injury and two approaches for stem cell administration

Trébol¹,

Georgiev-Hristov²,

Vega-Clemente³

et al. 2018

WJSC

View full text Add to dashboard Cite

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“…Given the current studies on MSCs' active role in aortic aneurysm and dissection ( 13 – 15 ), we hypothesis that MSCs in AD patient might have some deficits thus patients consequently manifest with insufficient repair and thus the repair-destruction balance is broken. As a matter of fact, some researchers suggested that the dysregulation of MSCs' activity may contribute to the disease ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

Transcriptome sequencing revealed candidate genes relevant to mesenchymal stem cells' role in aortic dissection patients

et al. 2017

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Aortic dissection (AD) results from the imbalance between synthesis and degradation of extracellular matrices in aortic wall, which is characterized by chronic inflammation. Mesenchymal stem cells (MSCs) are known for anti-inflammatory and repairing effects and have therefore been studied for treatment for numerous diseases, including AD. However, it is unclear which genes or signaling pathways contribute to MSCs' role in AD. In the present study, RNA sequencing (RNA-seq) was conducted between MSCs from patients with AS (AD-MSCs) and those from age-matched healthy donors (HD-MSCs). RNA-seq revealed 201 differentially expressed genes (DEGs) under the filter of fold change>2 and P-value <0.05, in which 93 genes were upregulated and 108 downregulated. We selectively verified 9 out of 201 DEGs via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) with an enlarged sample size. The trends of RT-qPCR results were consistent with RNA-seq data. Unsupervised hierarchical clustering of the 9-gene expression profiles enables the division of clinical samples into AD and HD groups. Kyoto Encyclopedia of Genes and Genomes analysis displayed a significant change in adhesion-related signaling pathways in AD-MSCs compared with HD-MSCs, whereas gene ontology analysis demonstrated DEGs were enriched in functions associated with development and morphogenesis, from a functional perspective. The present results indicate that gene expression profiles of AD-MSCs were significantly changed compared with HD-MSCs. These changes are probably associated with MSCs' adhesion capacity and development. These results may provide important insights into the role of MSCs in AD pathogenesis.

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“…Németh et al[ 86 ] observed MSC sepsis attenuation by macrophage reprogramming to increase IL-10, a cytokine that decreases neutrophil migration. Our research team has added contributions to that evidence: Georgiev-Hristov found an early shift from acute to chronic inflammation in the presence of ASCs (neutrophil descent and macrophage increment) after tracheal anastomosis[ 33 ], and Riera observed less acute and chronic inflammation during 3 mo, with the increasing fibrosis of the aneurysm sac in pigs[ 87 ]. Regeneration is not clearly demonstrated in many studies and is very difficult to observe; it may be that more complex morphometric or molecular analyses are needed to confirm it.…”

Section: Discussionmentioning

confidence: 99%

Stem cell therapy for faecal incontinence: Current state and future perspectives

Trébol¹,

Carabias-Orgaz²,

García-Arranz³

et al. 2018

WJSC

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Faecal continence is a complex function involving different organs and systems. Faecal incontinence is a common disorder with different pathogeneses, disabling consequences and high repercussions for quality of life. Current management modalities are not ideal, and the development of new treatments is needed. Since 2008, stem cell therapies have been validated, 36 publications have appeared (29 in preclinical models and seven in clinical settings), and six registered clinical trials are currently ongoing. Some publications have combined stem cells with bioengineering technologies. The aim of this review is to identify and summarise the existing published knowledge of stem cell utilization as a treatment for faecal incontinence. A narrative or descriptive review is presented. Preclinical studies have demonstrated that cellular therapy, mainly in the form of local injections of muscle-derived (muscle derived stem cells or myoblasts derived from them) or mesenchymal (bone-marrow- or adipose-derived) stem cells, is safe. Cellular therapy has also been shown to stimulate the repair of both acute and subacute anal sphincter injuries, and some encouraging functional results have been obtained. Stem cells combined with normal cells on bioengineered scaffolds have achieved the successful creation and implantation of intrinsically-innervated anal sphincter constructs. The clinical evidence, based on adipose-derived stem cells and myoblasts, is extremely limited yet has yielded some promising results, and appears to be safe. Further investigation in both animal models and clinical settings is necessary to drawing conclusions. Nevertheless, if the preliminary results are confirmed, stem cell therapy for faecal incontinence may well become a clinical reality in the near future.

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Potential of mesenchymal stem cell in stabilization of abdominal aortic aneurysm sac

Cited by 10 publications

References 22 publications

Rat model of anal sphincter injury and two approaches for stem cell administration

Rat model of anal sphincter injury and two approaches for stem cell administration

Transcriptome sequencing revealed candidate genes relevant to mesenchymal stem cells' role in aortic dissection patients

Stem cell therapy for faecal incontinence: Current state and future perspectives

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