Progenitors Systemically Transplanted into Neonatal Mice Localize to Areas of Active Bone Formation in vivo: Implications of Cell Therapy for Skeletal Diseases

¹ Pennsylvania State College of Medicine, Division of Musculoskeletal Sciences, Department of Orthopaedics & Rehabilitation, Hershey, Pennsylvania

^* To whom correspondence should be addressed. E-mail: cniyibizi{at}psu.edu.

	Abstract

The potential of cell or gene therapy to treat skeletal diseases was evaluated through analysis of transplanted osteoprogenitors into neonatal homozygous and heterozygous osteogenesis imperfecta mice (oim). The osteoprogenitors used for transplantation were prepared by injection of mesenchymal stem cells (MSCs) marked with the green fluorescent protein (GFP) into normal mice with the subsequent retrieval of the cells at 35 days. The retrieved cells referred to here as osteoprogenitors were expanded in culture and transplanted into the 2-day old oim mice via the superficial temporal vein. The recipient mice were evaluated at 2 and 4 weeks after cell transplantation. Four weeks after transplantation, tissue sections made from femurs and tibia of oim mice showed that the GFP positive (GFP+) cells were distributed on the surfaces of the bone spicules in the spongiosa, the area of active bone formation. In the diaphysis, the GFP+ cells were distributed in the bone marrow, on the endosteal surfaces and also in the cortical bone. Immunofluorescence localization for GFP, confirmed that the fluorescence seen in tissue sections was due to the engrafted donor cells, not bone autofluorescence. Gene expression analysis by PCR of the GFP+ cells retrieved from the bones and marrow of the recipient mice demonstrated that the cells from bone were osteoblasts, while those from bone marrow were progenitors. This data demonstrates that MSCs delivered systemically to developing OI mice engraft in bones, localize to areas of active bone formation, differentiate into osteoblasts in vivo, and may contribute to bone formation in vivo.

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