Abstract
Introduction: Erectile dysfunction (ED) is a major complication of type 2 diabetes, and many diabetic men with ED are refractory to common ED therapies. Aim: To determine whether autologous adipose tissue-derived stem cells (ADSCs) injected into the penis of impotent type 2 diabetic rats improve erectile function. Main Outcome Measures: Blood glucose levels, intracavernous pressure (ICP) increase upon cavernous nerve (CN) electrostimulation, and immunohistochemistry. Methods: Twenty-two male Zucker diabetic fatty (ZDF) rats were used. At 22 weeks of age, all the animals underwent unilateral CN electrostimulation and ICP measurement to confirm impotence. Paragonadal adipose tissue was harvested to procure ADSCs. The impotent animals were randomized to ADSC treatment and sham control groups. At 23 weeks of age, the treatment group animals underwent a penile injection of 1 million ADSCs; the control group animals received vehicle only. Erectile function studies were repeated at 26 weeks of age, followed by tissue harvest. Results: The rats developed diabetes within the first 10 weeks of age. At 22 weeks of age, 20 out of the 22 rats presented with ED. The post-treatment ICP increase during CN stimulation and ICP increase/mean arterial pressure were significantly higher in the treatment group compared with controls. Three weeks after injection into the corpus cavernosum, only a small number of BrdU-labeled ADSCs was detectable within corporal tissue of the treatment group. There was a significant increase in neuronal nitric oxide synthase (nNOS) in the penile dorsal nerve and in the number of endothelial cells in the corpora cavernosa of the rats in the treatment group. Conclusion: Autologous ADSCs injected into the penis were effective to improve erectile function and to alter the microarchitecture of the corpus cavernosum. Since the number of ADSCs retained in the corpus cavernosum is very small, we postulate that their paracrine function, not trans-differentiation to smooth muscle or endothelial cells, is responsible for the improvement in penile function.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 89-98 |
| Number of pages | 10 |
| Journal | Journal of Sexual Medicine |
| Volume | 7 |
| Issue number | 1 PART 1 |
| DOIs | |
| State | Published - Jan 2010 |
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Keywords
- Adipose tissue-derived stem cells
- Adult stem cells
- Erectile dysfunction
- Mesenchymal stem cells
- Regenerative therapy
- Type 2 diabetes
ASJC Scopus subject areas
- Urology
- Obstetrics and Gynecology
- Reproductive Medicine
Cite this
Treatment of erectile dysfunction in the obese Type 2 diabetic ZDF rat with adipose tissue-derived stem cells. / Garcia, Maurice M.; Fandel, Thomas M.; Lin, Guiting; Shindel, Alan W; Banie, Lia; Lin, Ching Shwun; Lue, Tom F.
In: Journal of Sexual Medicine, Vol. 7, No. 1 PART 1, 01.2010, p. 89-98.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Treatment of erectile dysfunction in the obese Type 2 diabetic ZDF rat with adipose tissue-derived stem cells
AU - Garcia, Maurice M.
AU - Fandel, Thomas M.
AU - Lin, Guiting
AU - Shindel, Alan W
AU - Banie, Lia
AU - Lin, Ching Shwun
AU - Lue, Tom F.
PY - 2010/1
Y1 - 2010/1
N2 - Introduction: Erectile dysfunction (ED) is a major complication of type 2 diabetes, and many diabetic men with ED are refractory to common ED therapies. Aim: To determine whether autologous adipose tissue-derived stem cells (ADSCs) injected into the penis of impotent type 2 diabetic rats improve erectile function. Main Outcome Measures: Blood glucose levels, intracavernous pressure (ICP) increase upon cavernous nerve (CN) electrostimulation, and immunohistochemistry. Methods: Twenty-two male Zucker diabetic fatty (ZDF) rats were used. At 22 weeks of age, all the animals underwent unilateral CN electrostimulation and ICP measurement to confirm impotence. Paragonadal adipose tissue was harvested to procure ADSCs. The impotent animals were randomized to ADSC treatment and sham control groups. At 23 weeks of age, the treatment group animals underwent a penile injection of 1 million ADSCs; the control group animals received vehicle only. Erectile function studies were repeated at 26 weeks of age, followed by tissue harvest. Results: The rats developed diabetes within the first 10 weeks of age. At 22 weeks of age, 20 out of the 22 rats presented with ED. The post-treatment ICP increase during CN stimulation and ICP increase/mean arterial pressure were significantly higher in the treatment group compared with controls. Three weeks after injection into the corpus cavernosum, only a small number of BrdU-labeled ADSCs was detectable within corporal tissue of the treatment group. There was a significant increase in neuronal nitric oxide synthase (nNOS) in the penile dorsal nerve and in the number of endothelial cells in the corpora cavernosa of the rats in the treatment group. Conclusion: Autologous ADSCs injected into the penis were effective to improve erectile function and to alter the microarchitecture of the corpus cavernosum. Since the number of ADSCs retained in the corpus cavernosum is very small, we postulate that their paracrine function, not trans-differentiation to smooth muscle or endothelial cells, is responsible for the improvement in penile function.
AB - Introduction: Erectile dysfunction (ED) is a major complication of type 2 diabetes, and many diabetic men with ED are refractory to common ED therapies. Aim: To determine whether autologous adipose tissue-derived stem cells (ADSCs) injected into the penis of impotent type 2 diabetic rats improve erectile function. Main Outcome Measures: Blood glucose levels, intracavernous pressure (ICP) increase upon cavernous nerve (CN) electrostimulation, and immunohistochemistry. Methods: Twenty-two male Zucker diabetic fatty (ZDF) rats were used. At 22 weeks of age, all the animals underwent unilateral CN electrostimulation and ICP measurement to confirm impotence. Paragonadal adipose tissue was harvested to procure ADSCs. The impotent animals were randomized to ADSC treatment and sham control groups. At 23 weeks of age, the treatment group animals underwent a penile injection of 1 million ADSCs; the control group animals received vehicle only. Erectile function studies were repeated at 26 weeks of age, followed by tissue harvest. Results: The rats developed diabetes within the first 10 weeks of age. At 22 weeks of age, 20 out of the 22 rats presented with ED. The post-treatment ICP increase during CN stimulation and ICP increase/mean arterial pressure were significantly higher in the treatment group compared with controls. Three weeks after injection into the corpus cavernosum, only a small number of BrdU-labeled ADSCs was detectable within corporal tissue of the treatment group. There was a significant increase in neuronal nitric oxide synthase (nNOS) in the penile dorsal nerve and in the number of endothelial cells in the corpora cavernosa of the rats in the treatment group. Conclusion: Autologous ADSCs injected into the penis were effective to improve erectile function and to alter the microarchitecture of the corpus cavernosum. Since the number of ADSCs retained in the corpus cavernosum is very small, we postulate that their paracrine function, not trans-differentiation to smooth muscle or endothelial cells, is responsible for the improvement in penile function.
KW - Adipose tissue-derived stem cells
KW - Adult stem cells
KW - Erectile dysfunction
KW - Mesenchymal stem cells
KW - Regenerative therapy
KW - Type 2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=74049113244&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=74049113244&partnerID=8YFLogxK
U2 - 10.1111/j.1743-6109.2009.01541.x
DO - 10.1111/j.1743-6109.2009.01541.x
M3 - Article
C2 - 20104670
AN - SCOPUS:74049113244
VL - 7
SP - 89
EP - 98
JO - Journal of Sexual Medicine
JF - Journal of Sexual Medicine
SN - 1743-6095
IS - 1 PART 1
ER -