Adipose-derived stem cells (MYSTEM® EVO Technology) as a treatment for complex transsphincteric anal fistula

Lobascio, Pierluigi; Balducci, G; Minafra, Marina; Laforgia, Rita; Fedele, Salvatore; Conticchio, Maria; Palasciano, Nicola

doi:10.1007/s10151-018-1785-2

Cited by 11 publications

(5 citation statements)

References 8 publications

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“…Other clinical applications have been highlighted in Table 5 [7, 15, 21, 22, 33–39, 47, 51, 54, 55, 57–59, 62, 67, 71–73, 76]. None of the authors reported the constituents of the cellular therapies used in these studies.…”

Section: Cell Concentrationsmentioning

confidence: 99%

The composition of cell-based therapies obtained from point-of-care devices/systems which mechanically dissociate lipoaspirate: a scoping review of the literature

et al. 2022

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Purpose Cell-based therapies using lipoaspirate are gaining popularity in orthopaedics due to their hypothesised regenerative potential. Several ‘point-of-care’ lipoaspirate-processing devices/systems have become available to isolate cells for therapeutic use, with published evidence reporting their clinical relevance. However, few studies have analysed the composition of their ‘minimally-manipulated’ cellular products in parallel, information that is vital to understand the mechanisms by which these therapies may be efficacious. This scoping review aimed to identify devices/systems using mechanical-only processing of lipoaspirate, the constituents of their cell-based therapies and where available, clinical outcomes. Methods PRISMA extension for scoping reviews guidelines were followed. MEDLINE, Embase and PubMed databases were systematically searched to identify relevant articles until 21st April 2022. Information relating to cellular composition and clinical outcomes for devices/systems was extracted. Further information was also obtained by individually searching the devices/systems in the PubMed database, Google search engine and contacting manufacturers. Results 2895 studies were screened and a total of 15 articles (11 = Level 5 evidence) fulfilled the inclusion criteria. 13 unique devices/systems were identified from included studies. All the studies reported cell concentration (cell number regardless of phenotype per millilitre of lipoaspirate) for their devices/systems (range 0.005–21 × 106). Ten reported cell viability (the measure of live cells- range 60–98%), 11 performed immuno-phenotypic analysis of the cell-subtypes and four investigated clinical outcomes of their cellular products. Only two studies reported all four of these parameters. Conclusion When focussing on cell concentration, cell viability and MSC immuno-phenotypic analysis alone, the most effective manual devices/systems were ones using filtration and cutting/mincing. However, it was unclear whether high performance in these categories would translate to improved clinical outcomes. Due to the lack of standardisation and heterogeneity of the data, it was also not possible to draw any reliable conclusions and determine the role of these devices/systems in clinical practice at present. Level of Evidence Level V Therapeutic.

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Section: Cell Concentrationsmentioning

confidence: 99%

The composition of cell-based therapies obtained from point-of-care devices/systems which mechanically dissociate lipoaspirate: a scoping review of the literature

et al. 2022

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“…In the tissue regeneration and repair of gastrointestinal disorders, including IBD, MSC transplantation has proven to be one of the most promising therapeutic methods [40]. Many clinical trials based on autologous/ allogeneic hADSCs for the treatment of Crohn's disease perianal fistula have been carried out [41][42][43][44][45][46][47][48][49][50][51][52][53], including long-term clinical follow-ups in multiple countries and centers around the world. These studies have observed that hADSCs have good therapeutic efficacy, but the mechanism by which MSCs treat enteritis and repair tissue damage has not been fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic efficacy of human adipose mesenchymal stem cells in Crohn’s colon fibrosis is improved by IFN-γ and kynurenic acid priming through indoleamine 2,3-dioxygenase-1 signaling

Zhang

et al. 2022

Stem Cell Res Ther

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Background Inflammatory bowel diseases (IBD) are chronic relapsing–remitting inflammatory diseases of the gastrointestinal tract that are typically categorized into two subtypes: Crohn's disease (CD) and ulcerative colitis (UC). Although MSCs therapy has achieved encouraging outcomes in IBD therapy, objective responses are limited in colon fibrosis stenosis owing to the complicated microenvironment of CD and MSCs heterogeneity of quality. Here, we chose IFN-γ and kynurenic acid (KYNA) to overcome the low response and heterogeneity of human adipose-derived MSCs (hADSCs) to treat IBD and expand the therapeutic effects based on the excellent ability of IFN-γ and KYNA to promote indoleamine 2,3-dioxygenase-1 (IDO-1) signaling, providing a potential protocol to treat IBD and fibrosis disease. Methods hADSCs were isolated, cultured, and identified from human abdominal adipose tissue. The CD pathology-like acute colitis and chronic colon fibrosis rat model was induced by 2,4,6-trinitrobenzen sulfonic acid (TNBS). hADSCs were pretreated in vitro with IFN-γ and KYNA and then were transplanted intravenously at day 1 and 3 of TNBS administration in colitis along with at day 1, 15, and 29 of TNBS administration in chronic colonic fibrosis. Therapeutic efficacy was evaluated by body weights, disease activity index, pathological staining, real-time PCR, Western blot, and flow cytometry. For knockout of IDO-1, hADSCs were transfected with IDO-1-targeting small gRNA carried on a CRISPR-Cas9-lentivirus vector. Results hADSCs treated with IFN-γ and KYNA significantly upregulated the expression and secretion of IDO-1, which has effectively ameliorated CD pathology-like colitis injury and fibrosis. Notably, the ability of hADSCs with IDO-1 knockout to treat colitis was significantly impaired and diminished the protective effects of the primed hADSCs with IFN-γ and KYNA. Conclusion Inflammatory cytokines IFN-γ- and KYNA-treated hADSCs more effectively alleviate TNBS-induced colitis and colonic fibrosis through an IDO-1-dependent manner. Primed hADSCs are a promising new strategy to improve the therapeutic efficacy of MSCs and worth further research.

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“…No obvious immune rejection response was found in our FIA model after rabbit ADMSC transplantation. Although it is no controversy for FIA patients to transplant their own ADMSCs at present [5], the allogeneic expanded adipose-derived stem cells (Cx601) have been used even in a phase III clinical trial [16, 29]. The results suggest that human ADMSCs can be produced in batches based on its immune exemption.…”

Section: Discussionmentioning

confidence: 99%

“…Males are affected twice as commonly as females [4]. Several surgical procedures to treat FIA have been developed in recent decades, but patients complain about discomfort and the prolonged healing period [5]. Cutting seton is a key method to treat complex anal fistula, which can protect sphincter function to some extent; however, the anal incontinence rate is still up to 34%-63%, and the postoperative pain is severe [6].…”

Section: Introductionmentioning

confidence: 99%

Adipose-Derived Stem Cells Are an Efficient Treatment for Fistula-in-ano of Japanese Rabbit

Qin

Wang

Huang

et al. 2019

Stem Cells International

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Fistula-in-ano (FIA, anal fistula) treatment remains a surgical challenge for coloproctologists. Adipose tissue-derived stem cells (ADSCs) are a new frontier in the treatment of FIA. In this study, we established a FIA model of Japanese rabbit and evaluated the effect of four treatments on fistula healing: ADSC transplantation, acellular small intestinal submucosa (ASIS), noncutting seton, and PBS as negative control. High-throughput RNA sequencing was also performed to investigate the anal tissue (normal and ADSC treatment group) expression profile of mRNA. Our data showed that ADSC treatment had the shortest time to promote fistula healing compared to the other treatments, and fistula filled with new adipose tissue and muscle cells without scar. Gene Ontology (GO) analysis of RNA-seq data showed that the differential genes are enriched in system development and animal organ development. Taken together, our findings demonstrate that ADSCs rapidly promote fistula healing through differentiation, a promising stem cell therapy for FIA. The rabbit is an effective animal model for evaluating FIA therapeutic options.

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Adipose-derived stem cells (MYSTEM® EVO Technology) as a treatment for complex transsphincteric anal fistula

Cited by 11 publications

References 8 publications

The composition of cell-based therapies obtained from point-of-care devices/systems which mechanically dissociate lipoaspirate: a scoping review of the literature

The composition of cell-based therapies obtained from point-of-care devices/systems which mechanically dissociate lipoaspirate: a scoping review of the literature

Therapeutic efficacy of human adipose mesenchymal stem cells in Crohn’s colon fibrosis is improved by IFN-γ and kynurenic acid priming through indoleamine 2,3-dioxygenase-1 signaling

Adipose-Derived Stem Cells Are an Efficient Treatment for Fistula-in-ano of Japanese Rabbit

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