Muscle-derived cells (MDCS) for augmenting or bulking urethral sphincter-muscle tissue
View Patent ↗The present invention provides muscle-derived cells, preferably myoblasts and muscle-derived stem cells, genetically engineered to contain and express one or more heterologous genes or functional segments of such genes, for delivery of the encoded gene products at or near sites of musculoskeletal, bone, ligament, meniscus, cartilage or genitourinary disease, injury, defect, or dysfunction. Ex vivo myoblast mediated gene delivery of human inducible nitric oxide synthase, and the resulting production of nitric oxide at and around the site of injury, are particularly provided by the invention as a treatment for lower genitourinary tract dysfunctions. Ex vivo gene transfer for the musculoskeletal system includes genes encoding acidic fibroblast growth factor, basic fibroblast growth factor, epidermal growth factor, insulin-like growth factor, platelet derived growth factor, transforming growth factor-1, transforming growth factor-a, nerve growth factor and interleukin-1 receptor antagonist protein (IRAP), bone morphogenetic protein (BMPs), cartilage derived morphogenetic protein (CDMPs), vascular endothelial growth factor (VEGF), and sonic hedgehog proteins.
1. A method of augmenting or bulking urethral sphincter muscle tissue in a recipient, comprising: introducing an isolated population of cells enriched in viable, non-fibroblast, desmin-expressing, autologous, skeletal muscle-derived myoblasts into urethral sphincter muscle tissue of the recipient in an amount sufficient for the myoblasts to augment or bulk the urethral sphincter muscle tissue.
2. The method according to claim 1 , wherein the skeletal muscle-derived myoblasts are introduced in a composition comprising a physiologically acceptable medium.
3. The method according to claim 1 , wherein the skeletal muscle-derived myoblasts are introduced in an amount of about 10 5 to 10 6 cells per cm 3 of tissue to be treated in physiologically acceptable medium.
4. The method according to claim 1 , wherein a cultured population of the skeletal muscle-derived myoblasts is introduced into the recipient.
5. The method according to claim 1 , wherein the skeletal muscle-derived myoblasts are contacted with a cytokine or growth factor selected from one or more of basic fibroblast growth factor (b-FGF), insulin-like growth factor (IGF), or nerve growth factor (NGF), prior to introducing the skeletal muscle-derived myoblasts into the recipient.
6. The method of claim 1 , wherein the augmenting or the bulking the urethral sphincter-muscle ameliorates a symptom associated with urethra in the recipient, wherein the symptom is stress urinary incontinence.
7. The method of claim 6 , wherein the recipient is a human.
8. The method of claim 1 , wherein the skeletal muscle-derived myoblasts are cultured to expand their number and are stored before being introduced to the urethral sphincter muscle tissue of said recipient.