The study is focused on evaluating the safety and efficacy of using vascular stromal tissue, derived from autologous adipose tissue, and subjected to microfragmentation and emulsification (Stromal Vascular Fraction Micro-Emulsion - tSVFem), in the treatment of chronic gastrointestinal fistulae (CGF). Tissue regeneration will be stimulated using 3D bio-printed scaffolds, enriched at implantation with mesenchymal stem cells derived from patients' adipose tissue; injection of tSVFem and scaffold placement will be performed endoscopically. The study proposes to use 3D bioprinting to create customized polymeric bioinks (gels) on supporting scaffolds that can serve as a framework for the growth and development of the patient's cells. This approach aims to promote tissue regeneration and integration, repair extensive CGF and restore the proper microbiota. A small portion of the patient's tSVFem will be injected in a bioreactor into the scaffolds and used for evaluation of the ability of the scaffolds to support cell proliferation, migration, and differentiation, as well as secretion of cytokines and growth factors and the immunological response. Also, to analyze the effect on cells and microbial species, the intestinal microbiota will be analyzed in a bioreactor under different dynamic conditions on the growth and differentiation of the MSCs contained in tsVFem, on the bio-printed scaffolds and the immunological results.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
tSVFem injection + 3D scaffold placement
Fondazione Policlinico Universitario Agostino gemelli IRCCS
Roma, Italy
Efficacy of the custom-made 3D printed vascular stromal tissue and scaffolds to treat CGFs.
Efficacy: endoscopic evaluation with or without radiological auxilium at 3 months after the procedure. Fistula will be described as: closed or still open. Further endoscopic evaluations with or without radiological auxilium could be repeated to assess maintenance of the closure.
Time frame: 24 months
Evaluation of immunological response
Exposure of the tSVFem-containing scaffolds to peripheral blood mononuclear cells obtained from the same patient. Microbiota analysis (obtained from stool sample of the patient) before and after the treatment. DNA extraction, metagenomics or 16S rRNA gene sequencing will be used to determine the diversity and abundance of the microbial community. Statistical analysis will be performed to identify specific microbial taxa that have changed significantly. PICRUSt2 and ALDEx2 tools will be applied to identify microbial signatures
Time frame: 24 months
Incidence of Treatment-Emergent Adverse Events
treatment-related adverse events as assessed by CTCAE v5.0 will be registered during follow-up
Time frame: 24 months
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