The fate of mesenchymal stem cells transplanted into immunocompetent neonatal mice: Implications for skeletal gene therapy via stem cells

Christopher Niyibizi, Sujing Wang, Zhibao Mi, Paul D. Robbins

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)955-963
Number of pages9
JournalMolecular Therapy
Volume9
Issue number6
DOIs
StatePublished - Jun 2004

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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