Histologic and urodynamic effects of autologous stromal vascular fraction extracted from fat tissue with minimal ex vivo manipulation on a porcine model of intrinsic sphincter deficiency

To evaluate the healing abilities of autologous stem cell therapy (stromal vascular fraction - SVF) prepared from adipose tissue using an automated system without an ex vivo culture phase in a pig model of intrinsic sphincteric deficiency (ISD).

Fifteen pigs were subjected to endoscopic section of the urethral sphincter. Animals were then randomly assigned to three groups: controls without injection of SVF, "early injection" (EI) with injection of SVF on 2-3 days following the section, and "late injection" (LI) delivery of SVF 30 days following the injury. Extraction and injection of SVF were performed in a single procedure. The SVF was characterized by flow cytometry. The mesenchymal stem cell-like cells (MSC-like) were enumerated by clonogenicity assay (CFU-F). End points included histological assessment of the surface of the urethral injury (SUrI), urodynamically, the maximum urethral pressure (MUP).

Flow cytometric analysis revealed a phenotype of MSC-like for 47.3% ±11.8% of SVF cells. CFU-F frequency was 1.3 to 6.6 per 100 SVF cells (1.3-6.6%). SVF injection was associated with a reduction of SUrI in EI and LI groups compared with respective controls (EI: 7% vs. 17%; p = 0.050 and LI: 1% vs. 13%; p = 0.029). On D30 after injection of SVF, MUP was significantly higher in the injected groups compared with the control group: 64% vs. 50% of D0 MUP (p = 0.04).

These data demonstrated the ability of autologous SVF to improve the urethral healing process in a large animal model of intrinsic sphincteric deficiency.

The Journal of urology. 2016 Jun 02 [Epub ahead of print]

R Boissier, J Magalon, F Sabatier, J Veran, L Giraudo, S Giusiano, S Garcia, F Dignat-George, L Arnaud, G Magalon, E Lechevallier, S Berdah, G Karsenty

Aix-Marseille University, 13284, Marseille, France; APHM, Conception University Hospital, Dept. of Urology and Kidney Transplantation, 13285, Marseille, France. Electronic address: ., APHM, Conception University Hospital, Dept. of Cell Therapy, INSERM CBT 1409, 13285, Marseille, France; Aix-Marseille University, INSERM UMR 1076, 13284, Marseille France., APHM, Conception University Hospital, Dept. of Cell Therapy, INSERM CBT 1409, 13285, Marseille, France; Aix-Marseille University, INSERM UMR 1076, 13284, Marseille France., APHM, Conception University Hospital, Dept. of Cell Therapy, INSERM CBT 1409, 13285, Marseille, France., APHM, Conception University Hospital, Dept. of Cell Therapy, INSERM CBT 1409, 13285, Marseille, France., Aix-Marseille University, 13284, Marseille, France; APHM, Nord University Hospital, Dept. of Pathology, 13015, Marseille, France., Aix-Marseille University, 13284, Marseille, France; APHM, Conception University Hospital, Dept. of Cell Therapy, INSERM CBT 1409, 13285, Marseille, France., APHM, Hospital Conception, Dept. of Biology and Hematology, 13285, Marseille, France., APHM, Hospital Conception, Dept. of Biology and Hematology, 13285, Marseille, France., Aix-Marseille University, 13284, Marseille, France; APHM, Conception University Hospital, Dept. of Plastic and Reconstructive Surgery, 13285, Marseille, France., Aix-Marseille University, 13284, Marseille, France; APHM, Conception University Hospital, Dept. of Urology and Kidney Transplantation, 13285, Marseille, France., Aix-Marseille University, 13284, Marseille, France; Aix-Marseille University, CERC - Center for Research and Teaching in Surgery, 13284, Marseille, France., Aix-Marseille University, 13284, Marseille, France; APHM, Conception University Hospital, Dept. of Urology and Kidney Transplantation, 13285, Marseille, France.