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

¹ Pennsylvania State University College of Medicine, Division of Musculoskeletal Sciences, Department of Orthopaedics and Rehabilitation Hershey, PA 17033, USA
² Pennsylvania State University College of Medicine, Division of Musculoskeletal Sciences, Department of Orthopaedics and Rehabilitation and Biochemistry and Molecular Biology, Hershey, PA 17033, USA

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

	Abstract

We evaluated a single cell expanded marrow derived progenitors for engraftment in a developing mouse model of osteogenesis imperfecta (OI) following systemic transplantation. The present studies were 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 GFP 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 comprised 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.

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