This study investigated the cellular and molecular characteristics of AT-MSCs obtained from autologous AT therapy in patients with high transphincteric perianal fistulas of crytoglandular origin. Adipose tissue was injected into anal fistulas. Characteristics of adipose tissue mesenchymal stemcells (AT-MSC) was investigated and compared in patients with fistula that healed after the treatment (responders) to patients who failed to heal (non-responders)
Injection with allogene or autologous stem cells has been reported to be efficient treatment of perianal fistulas. An alternative to this treatment could be injection with freshly collected autologous adipose tissue. In this study 27 patients with cryptoglandular anal fistulas were treated with freshly collected autologous adipose tissue.A clinical assessment of the patient prior to inclusion was undertaken and a loose seton placed for at least 6 weeks prior to fat injection. An MRI of the pelvis was performed before inclusion. Fistulas with secondary tracts and/or cavities were excluded. The operation was performed in one procedure including liposuction and injection of adipose tissue. A sample of adipose tissue from all 27 patients was analyzed. AT-MSCs were isolated and characterized using cellular and molecular analyses. Clinical and MRI-scanning evaluation of fistula healing and evaluation of ano-rectal function was performed after 6 months. AT-MSCs phenotype was compared between responders and non-responders with respect to fistula healing. The evaluation of the AT-MSCs was performed in a blinded manner.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
27
Investigation of cell proliferation of AT-MSCs
Cell proliferation of AT-MSCs evaluated as number of cells/per day
Time frame: At start of treatment
Investigation of differentiation potential of AT-MSCs to differentiate into adipocyte
Differentiation potential of AT-MSCs: to differentiate into adipocyte measured by Oil-Red O staining and gene expression of adipogenic markers (PPARg and LPL normalized to housekeeping gene beta actin) presented as a Fold change to undifferentiated cells (arbitrary units)
Time frame: At start of treatment
Investigation of differentiation potential of AT-MSCs to differentiate into osteoblast
Differentiation potential of AT-MSCs: to differentiate into osteoblast measured by Alizarin S staining and gene expression of osteogenic markers (BGALP and RUNX2 normalized to housekeeping gene beta actin) presented as a Fold change to undifferentiated cells (arbitrary units)
Time frame: At start of treatment
Measurement of gene expression profile of AT-MSCs
Gene expression of proinflammatory (NFKB, TNFa, IL1B, IL6) and senescence associated molecules(CDKN2A, TP53, TGFB1, VEGFA, IFNG, IL6) of AT-MSCs in relation to the outcome of fistula treatment (i.e. comparison between responders and non-responders). The data are normalized to housekeeping gene beta actin (arbitrary units)
Time frame: At start of treatment
Healing of anal fistula after treatment
Clinical healing defined as closure of the internal and external fistula opening and no discharge evaluated as success rate of the healing in (%)
Time frame: 6 months after last injection of autologous adipose tissue
Evaluation of fistula healing after treatment
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A combination of Clinical and MRI healing defined as closure of the internal and external fistula opening and no discharge and no fluid filled fistula tracts on evaluated as success rate of the healing in (%)
Time frame: 6 months after last injection of autologous adipose tissue
Functional gastroenterological outcome after treatment
Anal continence evaluated as the St. Mark's Score (0-24)
Time frame: 6 months after last injection of autologous adipose tissue
Defecation disorder evaluation after treatment
Defecation disorders evaluated as Altomare Obstructed Defecation Score (0-31)
Time frame: 6 months after last injection of autologous adipose tissue
Functional urological outcome after treatment
Urinary incontinence evaluated as ICIQ-UI-SF (0-21)
Time frame: 6 months after last injection of autologous adipose tissue