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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1717-1725. Prepublished online as a Blood First Edition Paper on October 29, 2007; DOI 10.1182/blood-2007-08-105809. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-08-105809v1 111/3/1717    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Guillot, P. V. Articles by Fisk, N. M. Search for Related Content PubMed PubMed Citation Articles by Guillot, P. V. Articles by Fisk, N. M. Related Collections Transplantation Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Intrauterine transplantation of human fetal mesenchymal stem cells from first-trimester blood repairs bone and reduces fractures in osteogenesis imperfecta mice Pascale V. Guillot1, Oyebode Abass1, J. H. Duncan Bassett2, Sandra J. Shefelbine3, George Bou-Gharios4, Jerry Chan1,5, Hitoshi Kurata1, Graham R. Williams2, Julia Polak5, and Nicholas M. Fisk1,6 1 Institute of Reproductive and Developmental Biology, 2 Division of Medicine and Medical Research Council (MRC) Clinical Sciences Centre, 3 Department of Bioengineering, 4 Department of Renal Medicine, and 5 Tissue Engineering and Regenerative Medicine Centre, Imperial College, South Kensington Campus, London; 6 Centre for Fetal Care, Queen Charlotte's & Chelsea Hospital, London, United Kingdom The inherited skeletal dysplasia osteogenesis imperfecta (OI) results in multiple fractures and is currently treated empirically. We transplanted human first-trimester fetal blood mesenchymal stem cells (MSCs) into homozygous oim mice in utero. This resulted in a two-thirds reduction in long bone fractures (P < .01), with fewer fractures per mouse (median 1, range 0-2 in mice that received transplants vs median 3, range 1-5 in mice that did not receive transplants by 12 weeks, P < .01). Nearly all mice that did not receive transplants had fractures (47 [97.9%] of 48), in contrast to 17 (58.6%) of 29 4- to 12-week-old mice that received transplants (P < .01). Transplantation was associated with increased bone strength (P < .01), thickness (P < .01), and length (P < .01), and normalization/reduction of growth plate height in 4- to 12-week-old oim was reduced in mice that underwent transplantion (P < .001). More donor cells were found in bone tissues compared with other organs (P < .001), with cells clustered in areas of active bone formation and remodeling, and at sites of fracture healing. Donor cells found in the bone expressed osteoblast lineage genes, and produced the extracellular bone structural protein osteopontin. Finally, MSC transplantation decreased bone hydroxyproline content. In conclusion, intrauterine transplantation of fetal MSCs markedly reduced fracture rates and skeletal abnormalities in a mouse model of the intermediate severity type III OI, suggesting a scientific basis for MSC treatment of affected human fetuses. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Fixing bones before birth Alan W. Flake Blood 2008 111: 978-979. [Full Text] [PDF] This article has been cited by other articles: C. Panaroni, R. Gioia, A. Lupi, R. Besio, S. A. Goldstein, J. Kreider, S. Leikin, J. C. Vera, E. L. Mertz, E. Perilli, et al. In utero transplantation of adult bone marrow decreases perinatal lethality and rescues the bone phenotype in the knockin murine model for classical, dominant osteogenesis imperfecta Blood, July 9, 2009; 114(2): 459 - 468. [Abstract] [Full Text] [PDF] F. Porta, F. Locatelli, and G. R. Burgio Hematopoietic stem cell transplantation: 40 years of continuous progress and evolution Haematologica, November 1, 2008; 93(11): 1607 - 1610. [Full Text] [PDF] J. Chan, S. Kumar, and N. M. Fisk First trimester embryo-fetoscopic and ultrasound-guided fetal blood sampling for ex vivo viral transduction of cultured human fetal mesenchymal stem cells Hum. Reprod., November 1, 2008; 23(11): 2427 - 2437. [Abstract] [Full Text] [PDF] M. A. Santos, K. O'Donoghue, J. Wyatt-Ashmead, and N. M Fisk Fetal cells in the maternal appendix: a marker of inflammation or fetal tissue repair? Hum. Reprod., October 1, 2008; 23(10): 2319 - 2325. [Abstract] [Full Text] [PDF]

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