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A COMPARATIVE ANALYSIS OF OPEN, LAPAROSCOPIC AND ROBOTIC RADICAL CYSTECTOMY FOR BLADDER CANCER
983
984
MUSCLE PROGENITOR CELLS FOR THE RESTORATION OF IRREVERSIBLY DAMAGED SPHINCTER FUNCTION
SPHINCTER REPAIR WITH AUTOLOGOUS SKELETAL MUSCLE DERIVED CELLS (MDC) - WHAT DO WE TRANSPLANT?
Eberli D.1, Yoo J.2, Soker S.2, Atala A.2
Otto T., Eimer C., Gerullis H.
1 University Hospital Zurich, Dept. of Urology, Zurich, Switzerland, 2Wake Forest Institute for Regenerative Medicine, Dept. of Urology, Winston-Salem, NC, United States of America
Lukas Clinics, Dept. of Urology, Neuss, Germany
Introduction & Objectives: Multiple treatment modalities, including surgeries and injection therapies have been tried for urinary incontinence. However, none of these methods is able to restore normal sphincter muscle function. We explored the possibility of achieving functional recovery of the urinary sphincter muscle using progenitor cells in a canine model. In addition, we explored the possibility of establishing a model of irreversibly damaged urinary sphincter function. Material & Methods: $ PRGHO RI XULQDU\ VSKLQFWHU LQVXᚑFLHQF\ ZDV FUHDWHG E\ micro surgically excising approximately 25% of the sphincter muscle in 26 dogs. Autologous progenitor muscle cells were grown and expanded in culture. Sphincteric function was assessed by urodynamic studies on normal and damaged sphincters. The culture expanded muscle progenitor cells were injected into the damaged sphincter muscle of 12 animals. The animals were followed for up to 6 months after injection, and urodynamic studies, functional organ bath studies, ultra structural, and histological examinations were performed. Results: Canine muscle progenitor cells were successfully and reproducibly isolated, grown and expanded. The animals injected with the cells showed a substantial improvement in sphincter function. Animals with MPC injection were able to recover the sphincter pressure to approximately 80% of normal, while the pressures in the control animals dropped and remained at 20%. Histologically, the implanted cells that ZHUHODEHOOHGZLWKWKHᚐXRUHVFHQWG\HWUDFHU3.+VXUYLYHGWRIRUPWLVVXHZLWKLQWKH LQMHFWHGUHJLRQRIWKHVSKLQFWHUDQGIRUPHGQHZLQQHUYDWHGPXVFOHᚏEHUV Conclusions: Autologous muscle progenitor cells are able to restore otherwise irreversibly damaged sphincter function in dogs. The injected cells are able to survive and form mature tissue within the damaged sphincter region. This study demonstrates the possibility of using autologous muscle precursor cells for the functional restoration RIXULQDU\VSKLQFWHUPXVFOHLQSDWLHQWVZLWKVSKLQFWHULQVXᚑFLHQF\
985
Introduction & Objectives: At our institute for tissue engineering, we perform successful sphincter repair by using MDC according to § 20 AMG (German pharmaceutical law). In order to study the nature of transplanted cells, we DQDO\]HG 0'& E\ LPPXQRF\WRFKHPLVWU\ IRU WKH H[SUHVVLRQ RI GLᚎHUHQW PDUNHUV LQYROYHG LQ PXVFOH FHOO GHYHORSPHQW DQG GLᚎHUHQWLDWLRQ 7KH VWXG\ ZDVDFFRPSOLVKHGLQᚏYHGLᚎHUHQWSDWLHQWV Material & Methods: Cells grown on chamber slides were rinsed in PBS, ᚏ[HGLQSDUDIRUPDOGHK\G3%6LQFXEDWHGLQ01+&OIROORZHGE\ LQFXEDWLRQLQEORFNLQJEXᚎHUFRQVLVWLQJRIERYLQHVHUXPDOEXPLQDQG Triton X-100/PBS for 15 minutes. Primary antibodies were: a-sarcomeric actin, DVPRRWKPXVFOHDFWLQGHVPLQ0\R'DQG&'$IWHUZDVKLQJFHOOVZHUH LQFXEDWHGZLWKᚐXRUHVFLQRU&<FRQMXJDWHGVHFRQGDU\DQWLERG\1XFOHLZHUH FRXQWHUVWDLQHGZLWK'$3,1HJDWLYHFRQWUROZHUHSHUIRUPHGXVLQJQRQVSHFLᚏF mouse IgG. Results: Five male patients (mean age:72.4 years, range:67-77) were enrolled LQWKHVWXG\$IWHUGD\VRIFHOOFXOWXUH UDQJH ZHUHYHDOHG0LR FHOOV UDQJH RIWKRVHFHOOV VWDQGDUGHUURURIPHDQ6(0 ZHUH SRVLWLYH IRU DVDUFRPHULF DFWLQ 6(0 IRU DVPRRWK PXVFOH DFWLQ DQG 6(0 IRU GHVPLQ &RLPPXQRVWDLQLQJ GHPRQVWUDWHG that 2.8% (SEM 0.5) of the MDC were positive for both a-sarcomeric actin and a-smooth muscle actin. The myogenic transcription factor MyoD1 was present LQ XS WR ZKLOH QR &' SRVLWLYH FHOOV ZHUH GHWHFWHG SDWLHQWV ZDV completely continent and 2 patients had an improvement from incontinence grade III to I. In 2 patients, no improvement was observed. Conclusions: Cells injected into the sphincter were 50% of myogenic origin. 7KHUHVLGXDOLVRIᚏEUREODVWRULJLQ7KHLGHQWLW\RIWKHWUDQVSODQWHGFHOOVZDV YHU\VLPLODULQGLᚎHUHQWSDWLHQWV
P61 TREATMENT OF ADVANCED STAGE BLADDER CANCER Friday, 28 March, 15.45-17.15, Blue Hall 2
986
EFFECT OF HUMAN ADIPOSE TISSUE-DERIVED STEM CELLS ON STRESS URINARY INCONTINENCE IN RATS
A COMPARATIVE ANALYSIS OF OPEN, LAPAROSCOPIC AND ROBOTIC RADICAL CYSTECTOMY FOR BLADDER CANCER
Kim K.H.1, Jung H.1, Yoon S.J.1, Lee M.S.1, Yun J.C.1, Park H.J.2, Kwon C.H.2, Ko I.G., Shin M.S., Kim C.J.
Elhage O.1, Keegan J.1, Challacombe B.1, Murphy D.1, Rimington P.2, Khan M.S.1, Dasgupta P.1
1 Gil Medical Centre, Gachon University of Medicine and Science, Dept. of Urology, Incheon, South Korea, 2Kangbuk Samsung Hospital , Sungkyunkwan University School of Medicine, Dept. of Urology, Seoul, South Korea, College of Medicine, Kyung Hee University, Dept. of Physiology, Seoul, South Korea
1
Introduction & Objectives: Stress urinary incontinence (SUI) states involuntary urinary leakage during activities such as exertion, sneezing, and coughing that increase abdominal pressure, and it is very common in women over middle age. For the treatment of urinary incontinence, many therapeutic trials such as surgical VXSSRUWDQGEXONLQJDJHQWVKDYHEHHQSHUIRUPHG5HFHQWO\WKHHᚎHFWVRIVHYHUDO kinds of tissue-derived stem cells for the incurable diseases have been examined DQG YHULᚏHG ,Q WKH SUHVHQW VWXG\ ZH LQYHVWLJDWHG WKH HᚎHFW RI KXPDQ DGLSRVH tissue-derived stem cells on SUI in rats. Material & Methods: Female Sprague-Dawley rats were anesthetized and their periurethral tissues were dissected (urethrolysis) to induce the rat model of urinary incontinence. The adipose aspirates were collected from female patients undergoing conventional liposuction and the adipose aspirates were processed to yield a pluripotent population of processed lipoaspirate (PLA) cells. After LPPXQRSKHQRW\SLQJ E\ ᚐRZ F\WRPHWULF DQDO\VLV 3/$ FHOOV ZHUH ᚐXRUHVFHQW labelled and injected on proximal urethra of the rats. The rats were divided into three groups: sham-operation group, urethrolysis group, urethrolysis & PLA cells injection group. At 8 weeks after injection of stem cells, leak point pressure was measured by using the pressure transducer after spinal cord transection at the level RI77WREORFNWKHUHᚐH[RIEODGGHUFRQWUDFWLRQV Results: ,QWKHSUHVHQWUHVXOWVOHDNSRLQWSUHVVXUHZDVVLJQLᚏFDQWO\GHFUHDVHGLQ the rats of urethrolysis group, while injection of human adipose tissue-derived stem cells increased the leak point pressure of urethrolysis-rats.
Guy’s & St Thomas’ Hospitals NHS Foundation Trust, Dept. of Urology, London, United Kingdom, 2Easbourne General Hospital, Dept. of Urology, Easbourne, United Kingdom Introduction & Objectives: With advancements in technology open radical cystectomy (ORC) is being challenged by the minimally invasive options RI ODSDURVFRSLF /5& DQG URERWLF UDGLFDO F\VWHFWRP\ 55& 7KLV LV WKH ᚏUVW reported comparison of the three techniques. Material & Methods: DJHPDWFKHG SDWLHQWV LQ HDFK JURXS KDG 25& LRC or RRC and ileal conduit diversion by three surgeons within a team over a 5 year period. Median data is presented in each category. Results: Op
Op timemins
Blood loss-mls
Complication %
Hosp staydays
Recoverywks
Oncologic follow-up
ORC
60
16
8
60% DF@5yr
LRC
50
16
60% DF@4yr
RRC
150
20
10.5
4
')#\U
DF = disease free either local or systemic mins = minutes op = operation wks = weeks Conclusions: RRC and LRC take longer than ORC but are associated with VLJQLᚏFDQWO\ OHVV EORRG ORVV DQG TXLFNHU UHFRYHU\ +RVSLWDO VWD\ LV VKRUWHVW for RRC which also has the lowest complication rate. The minimally invasive approaches do not appear to compromise cancer control at least in the medium term.
Conclusions: These results showed the possibility that human adipose tissueGHULYHGVWHPFHOOVFRXOGEHXVHGIRUWKHHᚎHFWLYHWKHUDSHXWLFPRGDOLW\WRDPHOLRUDWH the symptoms of urinary incontinence.
Eur Urol Suppl 2008;7(3):317
984
MUSCLE PROGENITOR CELLS FOR THE RESTORATION OF IRREVERSIBLY DAMAGED SPHINCTER FUNCTION
SPHINCTER REPAIR WITH AUTOLOGOUS SKELETAL MUSCLE DERIVED CELLS (MDC) - WHAT DO WE TRANSPLANT?
Eberli D.1, Yoo J.2, Soker S.2, Atala A.2
Otto T., Eimer C., Gerullis H.
1 University Hospital Zurich, Dept. of Urology, Zurich, Switzerland, 2Wake Forest Institute for Regenerative Medicine, Dept. of Urology, Winston-Salem, NC, United States of America
Lukas Clinics, Dept. of Urology, Neuss, Germany
Introduction & Objectives: Multiple treatment modalities, including surgeries and injection therapies have been tried for urinary incontinence. However, none of these methods is able to restore normal sphincter muscle function. We explored the possibility of achieving functional recovery of the urinary sphincter muscle using progenitor cells in a canine model. In addition, we explored the possibility of establishing a model of irreversibly damaged urinary sphincter function. Material & Methods: $ PRGHO RI XULQDU\ VSKLQFWHU LQVXᚑFLHQF\ ZDV FUHDWHG E\ micro surgically excising approximately 25% of the sphincter muscle in 26 dogs. Autologous progenitor muscle cells were grown and expanded in culture. Sphincteric function was assessed by urodynamic studies on normal and damaged sphincters. The culture expanded muscle progenitor cells were injected into the damaged sphincter muscle of 12 animals. The animals were followed for up to 6 months after injection, and urodynamic studies, functional organ bath studies, ultra structural, and histological examinations were performed. Results: Canine muscle progenitor cells were successfully and reproducibly isolated, grown and expanded. The animals injected with the cells showed a substantial improvement in sphincter function. Animals with MPC injection were able to recover the sphincter pressure to approximately 80% of normal, while the pressures in the control animals dropped and remained at 20%. Histologically, the implanted cells that ZHUHODEHOOHGZLWKWKHᚐXRUHVFHQWG\HWUDFHU3.+VXUYLYHGWRIRUPWLVVXHZLWKLQWKH LQMHFWHGUHJLRQRIWKHVSKLQFWHUDQGIRUPHGQHZLQQHUYDWHGPXVFOHᚏEHUV Conclusions: Autologous muscle progenitor cells are able to restore otherwise irreversibly damaged sphincter function in dogs. The injected cells are able to survive and form mature tissue within the damaged sphincter region. This study demonstrates the possibility of using autologous muscle precursor cells for the functional restoration RIXULQDU\VSKLQFWHUPXVFOHLQSDWLHQWVZLWKVSKLQFWHULQVXᚑFLHQF\
985
Introduction & Objectives: At our institute for tissue engineering, we perform successful sphincter repair by using MDC according to § 20 AMG (German pharmaceutical law). In order to study the nature of transplanted cells, we DQDO\]HG 0'& E\ LPPXQRF\WRFKHPLVWU\ IRU WKH H[SUHVVLRQ RI GLᚎHUHQW PDUNHUV LQYROYHG LQ PXVFOH FHOO GHYHORSPHQW DQG GLᚎHUHQWLDWLRQ 7KH VWXG\ ZDVDFFRPSOLVKHGLQᚏYHGLᚎHUHQWSDWLHQWV Material & Methods: Cells grown on chamber slides were rinsed in PBS, ᚏ[HGLQSDUDIRUPDOGHK\G3%6LQFXEDWHGLQ01+&OIROORZHGE\ LQFXEDWLRQLQEORFNLQJEXᚎHUFRQVLVWLQJRIERYLQHVHUXPDOEXPLQDQG Triton X-100/PBS for 15 minutes. Primary antibodies were: a-sarcomeric actin, DVPRRWKPXVFOHDFWLQGHVPLQ0\R'DQG&'$IWHUZDVKLQJFHOOVZHUH LQFXEDWHGZLWKᚐXRUHVFLQRU&<FRQMXJDWHGVHFRQGDU\DQWLERG\1XFOHLZHUH FRXQWHUVWDLQHGZLWK'$3,1HJDWLYHFRQWUROZHUHSHUIRUPHGXVLQJQRQVSHFLᚏF mouse IgG. Results: Five male patients (mean age:72.4 years, range:67-77) were enrolled LQWKHVWXG\$IWHUGD\VRIFHOOFXOWXUH UDQJH ZHUHYHDOHG0LR FHOOV UDQJH RIWKRVHFHOOV VWDQGDUGHUURURIPHDQ6(0 ZHUH SRVLWLYH IRU DVDUFRPHULF DFWLQ 6(0 IRU DVPRRWK PXVFOH DFWLQ DQG 6(0 IRU GHVPLQ &RLPPXQRVWDLQLQJ GHPRQVWUDWHG that 2.8% (SEM 0.5) of the MDC were positive for both a-sarcomeric actin and a-smooth muscle actin. The myogenic transcription factor MyoD1 was present LQ XS WR ZKLOH QR &' SRVLWLYH FHOOV ZHUH GHWHFWHG SDWLHQWV ZDV completely continent and 2 patients had an improvement from incontinence grade III to I. In 2 patients, no improvement was observed. Conclusions: Cells injected into the sphincter were 50% of myogenic origin. 7KHUHVLGXDOLVRIᚏEUREODVWRULJLQ7KHLGHQWLW\RIWKHWUDQVSODQWHGFHOOVZDV YHU\VLPLODULQGLᚎHUHQWSDWLHQWV
P61 TREATMENT OF ADVANCED STAGE BLADDER CANCER Friday, 28 March, 15.45-17.15, Blue Hall 2
986
EFFECT OF HUMAN ADIPOSE TISSUE-DERIVED STEM CELLS ON STRESS URINARY INCONTINENCE IN RATS
A COMPARATIVE ANALYSIS OF OPEN, LAPAROSCOPIC AND ROBOTIC RADICAL CYSTECTOMY FOR BLADDER CANCER
Kim K.H.1, Jung H.1, Yoon S.J.1, Lee M.S.1, Yun J.C.1, Park H.J.2, Kwon C.H.2, Ko I.G., Shin M.S., Kim C.J.
Elhage O.1, Keegan J.1, Challacombe B.1, Murphy D.1, Rimington P.2, Khan M.S.1, Dasgupta P.1
1 Gil Medical Centre, Gachon University of Medicine and Science, Dept. of Urology, Incheon, South Korea, 2Kangbuk Samsung Hospital , Sungkyunkwan University School of Medicine, Dept. of Urology, Seoul, South Korea, College of Medicine, Kyung Hee University, Dept. of Physiology, Seoul, South Korea
1
Introduction & Objectives: Stress urinary incontinence (SUI) states involuntary urinary leakage during activities such as exertion, sneezing, and coughing that increase abdominal pressure, and it is very common in women over middle age. For the treatment of urinary incontinence, many therapeutic trials such as surgical VXSSRUWDQGEXONLQJDJHQWVKDYHEHHQSHUIRUPHG5HFHQWO\WKHHᚎHFWVRIVHYHUDO kinds of tissue-derived stem cells for the incurable diseases have been examined DQG YHULᚏHG ,Q WKH SUHVHQW VWXG\ ZH LQYHVWLJDWHG WKH HᚎHFW RI KXPDQ DGLSRVH tissue-derived stem cells on SUI in rats. Material & Methods: Female Sprague-Dawley rats were anesthetized and their periurethral tissues were dissected (urethrolysis) to induce the rat model of urinary incontinence. The adipose aspirates were collected from female patients undergoing conventional liposuction and the adipose aspirates were processed to yield a pluripotent population of processed lipoaspirate (PLA) cells. After LPPXQRSKHQRW\SLQJ E\ ᚐRZ F\WRPHWULF DQDO\VLV 3/$ FHOOV ZHUH ᚐXRUHVFHQW labelled and injected on proximal urethra of the rats. The rats were divided into three groups: sham-operation group, urethrolysis group, urethrolysis & PLA cells injection group. At 8 weeks after injection of stem cells, leak point pressure was measured by using the pressure transducer after spinal cord transection at the level RI77WREORFNWKHUHᚐH[RIEODGGHUFRQWUDFWLRQV Results: ,QWKHSUHVHQWUHVXOWVOHDNSRLQWSUHVVXUHZDVVLJQLᚏFDQWO\GHFUHDVHGLQ the rats of urethrolysis group, while injection of human adipose tissue-derived stem cells increased the leak point pressure of urethrolysis-rats.
Guy’s & St Thomas’ Hospitals NHS Foundation Trust, Dept. of Urology, London, United Kingdom, 2Easbourne General Hospital, Dept. of Urology, Easbourne, United Kingdom Introduction & Objectives: With advancements in technology open radical cystectomy (ORC) is being challenged by the minimally invasive options RI ODSDURVFRSLF /5& DQG URERWLF UDGLFDO F\VWHFWRP\ 55& 7KLV LV WKH ᚏUVW reported comparison of the three techniques. Material & Methods: DJHPDWFKHG SDWLHQWV LQ HDFK JURXS KDG 25& LRC or RRC and ileal conduit diversion by three surgeons within a team over a 5 year period. Median data is presented in each category. Results: Op
Op timemins
Blood loss-mls
Complication %
Hosp staydays
Recoverywks
Oncologic follow-up
ORC
60
16
8
60% DF@5yr
LRC
50
16
60% DF@4yr
RRC
150
20
10.5
4
')#\U
DF = disease free either local or systemic mins = minutes op = operation wks = weeks Conclusions: RRC and LRC take longer than ORC but are associated with VLJQLᚏFDQWO\ OHVV EORRG ORVV DQG TXLFNHU UHFRYHU\ +RVSLWDO VWD\ LV VKRUWHVW for RRC which also has the lowest complication rate. The minimally invasive approaches do not appear to compromise cancer control at least in the medium term.
Conclusions: These results showed the possibility that human adipose tissueGHULYHGVWHPFHOOVFRXOGEHXVHGIRUWKHHᚎHFWLYHWKHUDSHXWLFPRGDOLW\WRDPHOLRUDWH the symptoms of urinary incontinence.
Eur Urol Suppl 2008;7(3):317