Soft tissue and bone augmentation and bulking utilizing muscle-derived progenitor cells, compositions and treatments thereof
The present invention provides muscle-derived progenitor cells that show long-term survival following transplantation into body tissues and which can augment soft tissue following introduction (e.g. via injection, transplantation, or implantation) into a site of soft tissue. Also provided are methods of isolating muscle-derived progenitor cells, and methods of genetically modifying the cells for gene transfer therapy. The invention further provides methods of using compositions comprising muscle-derived progenitor cells for the augmentation and bulking of mammalian, including human, soft tissues in the treatment of various cosmetic or functional conditions, including malformation, injury, weakness, disease, or dysfunction. In particular, the present invention provides treatments and amelioration for dermatological conditions, gastroesophageal reflux, vesico-ureteral reflux, urinary incontinence, fecal incontinence, heart failure, and myocardial infarction.
1. An isolated population of muscle-derived progenitor cells (MDCs), produced by the process of:
(a) plating a suspension of muscle cells from skeletal muscle tissue in a first container to which fibroblast cells of the muscle cell suspension adhere;
(b) re-plating slowly adhering cells from step (a) in a second container, wherein the slowly adhering cells do not adhere within about one hour of plating;
(c) repeating step (b) at least once; and
(d) isolating the MDCs from the walls of the container or suspension, wherein the MDCs give rise to osteogenic cell lineages and myogenic cell lineages.
2. The isolated population according to claim 1 , wherein step (b) is repeated at least five times, wherein the population of cells shows higher desmin expression than cells wherein step (b) is repeated less than five times.
3. The isolated population according to claim 1 , wherein the skeletal muscle tissue is mammalian skeletal muscle tissue.
4. The isolated population according to claim 3 , wherein the mammalian skeletal muscle tissue is human skeletal muscle tissue.
5. The isolated population according to claim 1 , wherein the population of cells shows greater than 95% desmin expression.