Bone augmentation utilizing muscle-derived progenitor compositions in biocompatible matrix, 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 non-soft tissue following introduction (e.g. via injection, transplantation, or implantation) into a site of non-soft tissue (e.g. bone) when combined with a biocompatible matrix, preferably SIS. The invention further provides methods of using compositions comprising muscle-derived progenitor cells with a biocompatible matrix for the augmentation and bulking of mammalian, including human, bone tissues in the treatment of various functional conditions, including osteoporosis, Paget's Disease, osteogenesis imperfecta, bone fracture, osteomalacia, decrease in bone trabecular strength, decrease in bone cortical strength and decrease in bone density with old age.
1. A method of repairing a calvarial defect with small intestine submucosa (SIS) seeded with muscle-derived progenitor cells (MDCs) in a mammalian subject in need thereof comprising:
(a) providing MDCs, wherein the MDCs are isolated by:
(i) isolating skeletal muscle from a mammal,
(ii) suspending the mammalian skeletal muscle in a medium in a first cell culture container for between 30 and 120 minutes thereby producing a cell population of adherent cells and a population of non-adherent cells;
(iii) decanting the medium and the population of the non-adherent cells from the first cell culture container to a second cell culture container;
(iv) allowing the population of the decanted non-adherent cells in the medium from the first cell culture container to attach to the walls of the second cell culture container for 1-3 days;
(v) isolating the population of cells from the walls of the second cell culture container, wherein the isolated cells are MDCs;
(b) providing SIS;
(c) seeding the SIS with the MDCs twelve hours before transplantation to the calvarial defect of the subject; and
(d) transplanting the MDC seeded SIS produced by step c to the calvarial defect of the mammalian subject;
thereby, repairing the calvarial defect in the mammalian subject in need thereof, wherein the MDCs express desmin.
2. The method of claim 1 , wherein the MDC is seeded onto a single layer SIS sheet and positioned in the interior of the bone.
3. The method of claim 1 , wherein the mammal is a human.
4. The method of claim 1 , wherein the MDCs are cultured to expand their number before being used to seed the SIS.
5. The method of claim 1 , wherein the calvarial defect is repaired by formation of new bone.
6. The method of claim 5 , wherein the new bone is formed within 4 weeks.
7. The method of claim 5 , wherein the new bone is formed within 10 weeks.