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TISSUE-SPECIFIC STEM CELLS

Distribution of Single-Cell Expanded Marrow Derived Progenitors in a Developing Mouse Model of Osteogenesis Imperfecta Following Systemic Transplantation

^aDepartment of Orthopaedics and Rehabilitation, Division of Musculoskeletal Sciences, and
^bDepartment of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA

Key Words. Progenitors • Osteogenesis imperfecta • Stem cell transplantation • Mouse model of osteogenesis imperfecta • Neonatal mice

Correspondence: Christopher Niyibizi, Ph.D., Department of Orthopaedics and Rehabilitation, Division of Musculoskeletal Sciences, Pennsylvania State University College of Medicine, H089, 500 University Drive, Hershey, Pennsylvania 17033, USA. Telephone: 717-531-5649; Fax: 717-531-7583; e-mail: Cniyibizi{at}psu.edu

Received June 21, 2007; accepted for publication August 27, 2007.
First published online in STEM CELLS EXPRESS   September 6, 2007.



We evaluated single-cell-expanded, marrow-derived progenitors for engraftment in a developing mouse model of osteogenesis imperfecta (OI) following systemic transplantation. The present study was initiated to evaluate the potential of mesenchymal stem cells to treat OI. Single-cell-derived progenitors were prepared from marrow stromal cells harvested from normal mice. Selected single-cell-expanded progenitors marked with green fluorescent protein were injected into the neonatal mouse model of OI, and the recipient mice were sacrificed at 2 and 4 weeks following cell transplantation. Examination of the tissues harvested from recipient mice at 2 and 4 weeks after cell transplantation demonstrated that the cells extravasated and engrafted in most of the bones as well as other tissues. Tissue sections made from the tibias and femurs of a selected recipient mouse showed that the cells were distributed in bone marrow, trabecular, and cortical bone as demonstrated by histology and confocal microscopy. The cells that engrafted in the bones of the recipient mouse synthesized and deposited type I collagen composed of 1(I) and 2(I) collagen heterotrimers. Genotyping and gene expression analysis of the cells retrieved from the bones of the recipient mouse at 2 and 4 weeks demonstrated that the cells expressed osteoblast-specific genes, suggesting that the donor cells differentiated into osteoblasts in vivo with no evidence of cell fusion. These data suggest that progenitors infused in developing mice will engraft in various tissues including bones, undergo differentiation, and deposit matrix and form bone in vivo.

Disclosure of potential conflicts of interest is found at the end of this article.

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