Yiou René, Yoo James J, Atala Anthony
Laboratory of Tissue Engineering and Cellular Therapeutics, Children's Hospital, Boston, MA, USA.
Transplantation. 2003 Oct 15;76(7):1053-60. doi: 10.1097/01.TP.0000090396.71097.C2.
Urinary incontinence is a debilitating condition that affects primarily elderly individuals. One major mechanism results from chronic denervation of the striated urethral sphincter with associated fibrosis. The authors investigated the fate of muscle precursor cells (MPC) injected into a model of striated urethral sphincter injury that reproduces the histopathologic changes of sphincter insufficiency.
The striated urethral sphincter of older male rats was damaged by electrocoagulation. MPC were isolated from limb myofiber explants, infected with an adenovirus carrying the transgene encoding beta-galactosidase, and injected into the sphincter of the same animal 37 days after injury. Animals were killed 5 and 30 days after injection for assessment of sphincter function and the formation of motor units.
Electrocoagulation resulted in an irreversible destruction of both sphincteric myofibers and nerve endings, with a functional incapacity of the damaged sphincter to sustain an increase in bladder pressure; atrophy and fibrosis developed after 1 month. Injection of MPC resulted in the formation of beta-galactosidase-expressing myotubes in the sphincter that persisted beyond 30 days. The regenerated myotubes carried acetylcholine receptors associated with a nerve ending and were thus considered to form anatomic motor units. Urodynamic studies confirmed the restoration of 41% of sphincter function 1 month after MPC injection.
The authors showed that MPC isolated from limb muscles of an older animal can recapitulate a myogenic program when injected into an irreversibly injured sphincter. The maturation of MPC activates nerve regeneration and restores functional motor units.
尿失禁是一种主要影响老年人的使人衰弱的病症。一种主要机制是由于横纹肌尿道括约肌的慢性去神经支配及相关纤维化所致。作者研究了注射到横纹肌尿道括约肌损伤模型中的肌肉前体细胞（MPC）的命运，该模型再现了括约肌功能不全的组织病理学变化。
用电凝法损伤老年雄性大鼠的横纹肌尿道括约肌。从肢体肌纤维外植体中分离出MPC，用携带编码β-半乳糖苷酶转基因的腺病毒感染，并在损伤后37天注射到同一动物的括约肌中。在注射后5天和30天处死动物，以评估括约肌功能和运动单位的形成。
电凝导致括约肌肌纤维和神经末梢的不可逆破坏，受损括约肌无法维持膀胱压力升高；1个月后出现萎缩和纤维化。注射MPC导致括约肌中形成表达β-半乳糖苷酶的肌管，且持续超过30天。再生的肌管带有与神经末梢相关的乙酰胆碱受体，因此被认为形成了解剖学运动单位。尿动力学研究证实，注射MPC后1个月，括约肌功能恢复了41%。
作者表明，从老年动物肢体肌肉中分离出的MPC注射到不可逆损伤的括约肌中时，能够重现肌源性程序。MPC的成熟激活神经再生并恢复功能性运动单位。
