Intrauterine transplantation of human fetal mesenchymal stem cells from first-trimester blood repairs bone and reduces fractures in osteogenesis impertecta mice

被引:129
作者
Guillot, Pascale V. [1 ]
Abass, Oyebode [1 ]
Bassett, J. H. Duncan [2 ]
Shefelbine, Sandra J. [3 ]
Bou-Gharios, George [4 ]
Chan, Jerry [1 ,5 ]
Kurata, Hitoshi [1 ]
Williams, Graham R. [2 ]
Polak, Julia [5 ]
Fisk, Nicholas M. [1 ,6 ]
机构
[1] Imperial Coll London, Inst Reprod & Dev Biol, London, England
[2] Imperial Coll London, Ctr Clin Sci, MRC, Div Med, London, England
[3] Imperial Coll London, Dept Bioengn, London, England
[4] Imperial Coll London, Dept Renal Med, London, England
[5] Imperial Coll London, Tissue Engn & Regenerat Med Ctr, London, England
[6] Queen Charlottes & Chelsea Hosp, Ctr Fetal Care, London, England
基金
英国医学研究理事会;
关键词
D O I
10.1182/blood-2007-08-105809
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The inherited skeletal dysplasia osteogenesis imperfecta (01) 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 hydroxyprolin content. In conclusion, intrauterine transplantation of fetal MSCs markedly reduced fracture rates and skeletal abnormalities in a mouse model of the intermediate severity type 111 01, suggesting a scientific basis for MSC treatment of affected human fetuses. (Blood. 2008;111: 1717-1725). (C) 2008 by The American Society of Hematology.
引用
收藏
页码:1717 / 1725
页数:9
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