Fibrin glue with autogenic bone marrow mesenchymal stem cells for urethral injury repair in rabbit model.
OBJECTIVE
Fibrin glue has been used for tissue adhesives and wound sealing. This study aimed to establish an approach to treat rabbit urethral injuries using fibrin glue and mesenchymal stem cells (MSCs).


METHODS
Rabbit urethral injury was performed by excising the subcutaneous tissue from the ventral aspect of the penile urethra. Thirty-six New Zealand rabbits were divided into four groups: injured without treatment (control), glue treatment (glue), glue and MSCs treatment (glue + MSCs), and without injury (normal). Animals were sacrificed and the penises were excised for analysis after treatment for 10 days (n=4) and 30 days (n=5).


RESULTS
The fibrin glue had a porous structure with cellular compatibility to MSCs. Two rabbits developed urethral fistulae in the control group, but none did in either the glue or the glue + MSCs groups at day 10 and 30. Hematoxylin and eosin staining showed that the distance between the skin and the epithelial layer at the ventral aspect of the penis increased in the glue and glue + MSCs groups compared to the control group at day 10 and 30. The density of blood vessels in the injured area increased in the glue and glue + MSCs groups compared to the control at day 10 and 30. The average thickness of the epithelial layer in the glue + MSCs group showed the same increasing trend among the three groups at day 10 and 30. The thickness and the area of the smooth muscle that surrounds the urethral mucosa at the operative region increased compared to the thickness in the control and glue groups at day 10 and 30. Pancytokeratins (AE1/AE3) staining showed weak signals in the urethral fistulae in the control group compared with the glue and glue + MSCs groups. The transplanted MSCs have differentiated into endothelial and smooth muscle cells, contributing to the formation of blood vessels and the recovery of urethral smooth muscle.


CONCLUSIONS
MSCs combined with fibrin glue showed improved neovascularization and smooth muscle formation in repairing urethral injury, resulting in effective prevention of the development of urethral fistulae. Our data indicate that fibrin glue combined with MSCs may be a feasible approach for repairing urethral injury.
State Key Laboratory of Medicinal Chemical Biology, The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin, China.
Kai
K
Wang
Yong
Y
Guan
Yi
Y
Liu
Meifeng
M
Zhu
Ting
T
Li
Di
D
An
Lailiang
L
Ou
Yongzhe
Y
Che
Guorong
G
Zhang
Jun
J
Zhang
Xi-Long
XL
Zheng
Deling
D
Kong
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D017577:Cutaneous Fistula / Q000209:etiology; D015718:Fibrin Tissue Adhesive / Q000494:pharmacology; D006085:Graft Survival; D008297:Male; D008422:Materials Testing; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000187:drug effects; D009092:Mucous Membrane / Q000473:pathology; D024510:Muscle Development; D009130:Muscle, Smooth / Q000473:pathology / Q000502:physiology*; D018919:Neovascularization, Physiologic; D011183:Postoperative Complications / Q000209:etiology; D011817:Rabbits; D012038:Regeneration / Q000187:drug effects*; D014182:Transplantation, Autologous; D014521:Urethra / Q000293:injuries / Q000473:pathology / Q000601:surgery*; D014522:Urethral Diseases / Q000209:etiology; D014548:Urinary Fistula / Q000209:etiology; D014945:Wound Healing
D015718:Fibrin Tissue Adhesive