The fate of mesenchymal stem cells transplanted into immunocompetent neonatal mice: implications for skeletal gene therapy via stem cells.
To explore the feasibility of skeletal gene and cell therapies, we transduced murine bone marrow-derived mesenchymal stem cells (MSCs) with a retrovirus carrying the enhanced green fluorescent protein and zeocin-resistance genes prior to transplantation into 2-day-old immunocompetent neonatal mice. Whole-body imaging of the recipient mice at 7 days post-systemic cell injection demonstrated a wide distribution of the cells in vivo. Twenty-five days posttransplantation, most of the infused cells were present in the lung as assessed by examination of the cells cultured from the lungs of the recipient mice. The cells persisted in lung and maintained a high level of gene expression and could be recovered from the recipient mice at 150 days after cell transplantation. A significant number of GFP-positive cells were also present in the bones of the recipient mice at 35 days post-cell transplantation. Recycling of the cells recovered from femurs of the recipient mice at 25 days posttransplantation by repeated injections into different neonatal mice resulted in the isolation of a clone of cells that was detected in bone and cartilage, but not in lung and liver after systemic injection. These data demonstrate that MSCs persist in immunocompetent neonatal mice, maintain a high level of gene expression, and may participate in skeletal growth and development of the recipient animals.
Niyibizi
Christopher
C
Department of Orthopaedics and Rehabilitation, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA. cniyibizi@psu.edu
Wang
Sujing
S
Mi
Zhibao
Z
Robbins
Paul D
PD
D000818:Animals; D000831:Animals, Newborn; D000954:Antigens, Surface / Q000032:analysis; D001847:Bone Diseases / Q000628:therapy*; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D002356:Cartilage / Q000737:chemistry / Q000166:cytology; D002465:Cell Movement; D024043:Collagen Type II / Q000032:analysis; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D007121:Immunocompetence; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000502:physiology; D051379:Mice; D012190:Retroviridae / Q000235:genetics; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D000954:Antigens, Surface; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D024043:Collagen Type II; D016212:Transforming Growth Factor beta; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins