TY - JOUR
T1 - The fate of mesenchymal stem cells transplanted into immunocompetent neonatal mice
T2 - Implications for skeletal gene therapy via stem cells
AU - Niyibizi, Christopher
AU - Wang, Sujing
AU - Mi, Zhibao
AU - Robbins, Paul D.
N1 - Funding Information:
This work was supported in part by NIH Grant R01 AR049688 and a grant from the Children’s Brittle Bone Foundation to C.N. The authors thank Dr. Simon Watkins and Dr. Glenn Papworth of University of Pittsburgh for the help with the whole-body imaging.
PY - 2004/6
Y1 - 2004/6
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ymthe.2004.02.022
DO - 10.1016/j.ymthe.2004.02.022
M3 - Article
C2 - 15194062
AN - SCOPUS:3042775005
SN - 1525-0016
VL - 9
SP - 955
EP - 963
JO - Molecular Therapy
JF - Molecular Therapy
IS - 6
ER -