Reconstruction of radical prostatectomy-induced urethral damage using skeletal muscle-derived multipotent stem cells.
BACKGROUND
Postoperative damage of the urethral rhabdosphincter (URS) and neurovascular bundle (NVB) is a major operative complication of radical prostatectomy. It is generally recognized to be caused by unavoidable surgical damage to the muscle-nerve-blood vessel units around the urethra. We attempted to treat this damage using skeletal muscle-derived stem cells, which are able to reconstitute muscle-nerve-blood vessel units.


METHODS
Cells were enzymatically extracted and sorted by flow cytometry as CD34/45 (Sk-34) and CD34/45 (Sk-DN) cells from green fluorescent protein transgenic mice and rats. URS-NVB damage was induced by manually removing one-third of the total URS and unilateral invasion of NVB in wild-type Sprague-Dawley and node rats. Freshly isolated Sk-34, Sk-34+Sk-DN cells, and cultured Sk-DN cells were directly transplanted into the damaged portion.


RESULTS
At 4 and 12 weeks after transplantation, urethral pressure profile by electrical stimulation through the sacral surface (L6-S1) was evaluated as functional recovery. The recovery ratio in the control and transplanted groups was 37.6% and 72.9%, at 4 weeks, and 41.6% and 78.4% at 12 weeks, respectively (P<0.05). Immunohistochemical and immunoelectron microscopic analysis revealed that transplanted cells differentiated into numerous skeletal muscle fibers having neuromuscular junctions (innervation) and nerve bundle-related Schwann cells and perineurium, and blood vessel-related endothelial cells and pericyte around the urethra.


CONCLUSIONS
Thus, we conclude that transplantation of skeletal muscle-derived multipotent Sk-34 and Sk-DN cells is potentially useful for the reconstitution of postoperative damage of URS and NVB after radical prostatectomy.
Hoshi
Akio
A
Department of Urology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Tamaki
Tetsuro
T
Tono
Kayoko
K
Okada
Yoshinori
Y
Akatsuka
Akira
A
Usui
Yukio
Y
Terachi
Toshiro
T
D000818:Animals; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D007150:Immunohistochemistry; D007431:Intraoperative Complications; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016253:Microscopy, Immunoelectron; D039902:Multipotent Stem Cells / Q000637:transplantation*; D018482:Muscle, Skeletal / Q000166:cytology* / Q000637:transplantation; D011468:Prostatectomy / Q000009:adverse effects*; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D019651:Plastic Surgery Procedures / Q000379:methods*; D020127:Recovery of Function; D033581:Stem Cell Transplantation / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014521:Urethra / Q000293:injuries* / Q000473:pathology / Q000601:surgery; D014563:Urodynamics / Q000502:physiology