Histological and Urodynamic Effects of Autologous Stromal Vascular Fraction Extracted from Fat Tissue with Minimal Ex Vivo Manipulation in a Porcine Model of Intrinsic Sphincter Deficiency.
OBJECTIVE
To evaluate the healing abilities of autologous stem cell therapy (stromal vascular fraction) prepared from adipose tissue we used an automated system without an ex vivo culture phase in a pig model of intrinsic sphincteric deficiency.


METHODS
A total of 15 pigs underwent endoscopic section of the urethral sphincter. Animals were then randomly assigned to 3 groups, including 1) controls without stromal vascular fraction injection, 2) early injection with stromal vascular fraction 2 to 3 days after section and 3) late stromal vascular fraction injection delivery 30 days after injury. Extraction and stromal vascular fraction injection were performed as a single procedure. The stromal vascular fraction was characterized by flow cytometry. Mesenchymal stem cell-like cells were enumerated by clonogenicity (cfu fibroblast) assay. Study end points included histological assessment of the urethral injury surface and urodynamics to determine maximum urethral pressure.


RESULTS
Flow cytometry analysis revealed a mesenchymal stem cell-like phenotype in a mean ± SD of 47.3% ± 11.8% of stromal vascular fraction cells. The cfu fibroblast frequency was 1.3 to 6.6/100 stromal vascular fraction cells (1.3% to 6.6%). Stromal vascular fraction injection was associated with a reduction of the urethral injury surface in the early and late injection groups compared with the respective controls (7% vs 17% and 1% vs 13%, p = 0.050 and 0.029, respectively). On day 30 after injection maximum urethral pressure was significantly higher in the injected groups than in the control group, that is 64% vs 50% of maximum urethral pressure on day 0 (p = 0.04).


CONCLUSIONS
These data demonstrate the ability of an autologous stromal vascular fraction to improve the urethral healing process in a large animal model of intrinsic sphincteric deficiency.
Aix-Marseille University, 13284, Marseille, France; Department of Urology and Kidney Transplantation, 13285, Assistance Publique Hôpitaux de Marseille, Marseille, France. Electronic address: romain.boissier@ap-hm.fr.
Romain
R
Boissier
Institut national de la santé et de la recherche médicale Unités mixtes de recherche 1076, Aix-Marseille University, 13284, Marseille, France; Department of Cell Therapy, Institut national de la santé et de la recherche médicale Unités mixtes de recherche 1076, 13285, Assistance Publique Hôpitaux de Marseille, Marseille, France; Center for Research and Cliniques en biothérapies 1409, 13285, Assistance Publique Hôpitaux de Marseille, Marseille, France.
Jeremy
J
Magalon
Institut national de la santé et de la recherche médicale Unités mixtes de recherche 1076, Aix-Marseille University, 13284, Marseille, France; Department of Cell Therapy, Institut national de la santé et de la recherche médicale Unités mixtes de recherche 1076, 13285, Assistance Publique Hôpitaux de Marseille, Marseille, France; Center for Research and Cliniques en biothérapies 1409, 13285, Assistance Publique Hôpitaux de Marseille, Marseille, France.
Florence
F
Sabatier
Center for Research and Cliniques en biothérapies 1409, 13285, Assistance Publique Hôpitaux de Marseille, Marseille, France.
Julie
J
Veran
Center for Research and Cliniques en biothérapies 1409, 13285, Assistance Publique Hôpitaux de Marseille, Marseille, France.
Laurent
L
Giraudo
Aix-Marseille University, 13284, Marseille, France; Center for Research and Cliniques en biothérapies 1409, 13285, Assistance Publique Hôpitaux de Marseille, Marseille, France; Department of Pathology, 13015, Assistance Publique Hôpitaux de Marseille, Nord University Hospital, Marseille, France.
Sophie
S
Giusiano
Aix-Marseille University, 13284, Marseille, France.
Stephane
S
Garcia
Department of Biology and Hematology, 13285, Assistance Publique Hôpitaux de Marseille, Hospital Conception, Marseille, France.
Françoise
F
Dignat-George
Department of Biology and Hematology, 13285, Assistance Publique Hôpitaux de Marseille, Hospital Conception, Marseille, France.
Laurent
L
Arnaud
Aix-Marseille University, 13284, Marseille, France; Department of Plastic and Reconstructive Surgery, 13285, Assistance Publique Hôpitaux de Marseille, Marseille, France.
Guy
G
Magalon
Aix-Marseille University, 13284, Marseille, France; Department of Urology and Kidney Transplantation, 13285, Assistance Publique Hôpitaux de Marseille, Marseille, France.
Eric
E
Lechevallier
Center for Research and Teaching in Surgery, Aix-Marseille University, 13284, Marseille, France; Aix-Marseille University, 13284, Marseille, France.
Stephane
S
Berdah
Aix-Marseille University, 13284, Marseille, France; Department of Urology and Kidney Transplantation, 13285, Assistance Publique Hôpitaux de Marseille, Marseille, France.
Gilles
G
Karsenty
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D004195:Disease Models, Animal; D033581:Stem Cell Transplantation / Q000379:methods*; D013552:Swine; D014521:Urethra / Q000473:pathology / Q000503:physiopathology*; D014550:Urinary Incontinence, Stress / Q000503:physiopathology / Q000601:surgery*; D014563:Urodynamics / Q000502:physiology*
adipose tissue; cell- and tissue-based therapy; stem cells; urethra; urinary incontinence