Journal
STEM CELLS TRANSLATIONAL MEDICINE
Volume 1, Issue 1, Pages 70-78Publisher
ALPHAMED PRESS
DOI: 10.5966/sctm.2011-0007
Keywords
CXCR4; Stem cell transplantation; Mesenchymal stem cells; SDF1; Fetal stem cells; Osteogenesis imperfecta
Categories
Funding
- Genesis ResearchTrust
- Henry Smith Charity
- Action Medical Research
- Research Council United Kingdom
- Kidney Research United Kingdom
- Medical Research Council
- Great Ormond Street Hospital Children's Charity
- Rosetrees Trust
- Action Medical Research [1749] Funding Source: researchfish
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Stem cells have considerable potential to repair damaged organs and tissues. We previously showed that prenatal transplantation of human first trimester fetal blood mesenchymal stem cells (hfMSCs) in a mouse model of osteogenesis imperfecta (oim mice) led to a phenotypic improvement, with a marked decrease in fracture rate. Donor cells differentiated into mature osteoblasts, producing bone proteins and minerals, including collagen type I alpha 2, which is absent in nontransplanted mice. This led to modifications of the bone matrix and subsequent decrease of bone brittleness, indicating that grafted cells directly contribute to improvement of bone mechanical properties. Nevertheless, the therapeutic effect was incomplete, attributing to the limited level of engraftment in bone. In this study, we show that although migration of hfMSCs to bone and bone marrow is CXCR4-SDF1 (SDF1 is stromal-derived factor) dependent, only a small number of cells present CXCR4 on the cell surface despite high levels of internal CXCR4. Priming with SDF1, however, upregulates CXCR4 to increase the CXCR4(+) cell fraction, improving chemotaxis in vitro and enhancing engraftment in vivo at least threefold in both oim and wild-type bone and bone marrow. Higher engraftment in oim bones was associated with decreased bone brittleness. This strategy represents a step to improve the therapeutic benefits of fetal cell therapy toward being curative. STEM CELLS TRANSLATIONAL MEDICINE 2012;1:70-78
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