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TISSUE-SPECIFIC STEM CELLS

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

Division of Musculoskeletal Sciences, Department of Orthopaedics and Rehabilitation, Penn State College of Medicine, Hershey, Pennsylvania, USA

Key Words. Osteogenesis imperfecta • Cell therapy • Progenitors • Mesenchymal stem cells

Correspondence: Christopher Niyibizi, Ph.D., Departments of Orthopedics and Rehabilitation and Biochemistry and Molecular Biology, Division of Musculoskeletal Sciences, Penn State College of Medicine, Mail Code H089, 500 University Drive, Hershey, Pennsylvania 17033, USA. Telephone: 717-531-5649; Fax: 717-531-7583; e-mail: cniyibizi{at}psu.edu

Received September 2, 2005; accepted for publication April 28, 2006.
First published online in STEM CELLS EXPRESS   May 4, 2006.



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 tibias 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 polymerase chain reaction of the GFP⁺ cells retrieved from the bones and marrow of the recipient mice demonstrated that the cells from bone were osteoblasts, whereas those from bone marrow were progenitors. These data demonstrate that MSCs delivered systemically to developing osteogenesis imperfecta 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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