Ex Vivo Gene Therapy to Produce Bone Using Different Cell Types

Bone formation following transplantation of genetically modified primary bone marrow stromal cells

“…In addition, Musgrave et al compared the bone formation by five different types of BMP-2-transduced cells (immortalized osteogenesis imperfecta marrow stromal cells, primary muscle derived cells, primary bone marrow stromal cells, articular condrocytes and skin fibroblasts) and found that bone marrow stromal cells reportedly have less ability to induce new bone than immortalized osteogenesis imperfecta marrow stromal cells or muscle derived cells [22]. These investigators injected 5.0 x lo5 cells infected with recombinant adenovirus (MOI = 50) into the muscles of adult severe combined immune deficient mice.…”

Muscle-derived stem cells

“…21 Since this discovery, several researchers have transduced murine candidate MDSCs with an adenovirus encoding for BMP-2, and transplanted the cells into an allogeneic host to demonstrate bone matrix formation and cellular differentiation into osteoblasts and osteocytes. [22][23][24] In particular, Lee et al 22 demonstrated that genetic engineering of the musclederived cells provided an effective cellular therapy in healing a critical-size skull bone defect. Additionally, muscle-derived cells showed improved cartilage healing in comparison to chondrocytes when seeded on to collagen gel scaffolds and placed into a full-thickness cartilage defect.…”

Transfer and Stable Transgene Expression of a Mammalian Artificial Chromosome into Bone Marrow‐Derived Human Mesenchymal Stem Cells

“…This list includes the replacement of genes to correct acquired or inherited disorders of bone, muscle, or cartilage by transfer of genes encoding bone morphogenic proteins -2, -4, -9 [21,[32][33][34][35][36][37][38][39][40], the transfer of genes encoding the blood coagulation factors VIII and IX for the treatment of hemophilia [41][42][43][44][45][46][47], human growth hormone [46,48], insulin-like growth factor 1 [49], and interleukin-3 [50]. This list also includes: erythropoietin [51], α-l-iduronidase for treatment of mucopolysaccharidosis type I [52], proα2 collagen (I) for treatment of osteogenesis imperfecta [53], sox9 [54] to enhance chondrogenesis, and interferon to treat tumors [55].…”