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

Guillot, PV, Abass, O, Bassett, JHD, Shefelbine, SJ, Bou-Gharios, G, Chan, J, Kurata, H, Williams, GR, Polak, J and Fisk, NM (2008) Intrauterine transplantation of human fetal mesenchymal stem cells from first-trimester blood repairs bone and reduces fractures in osteogenesis imperfecta mice. Blood, 111 3: 1717-1725. doi:10.1182/blood-2007-08-105809


Author Guillot, PV
Abass, O
Bassett, JHD
Shefelbine, SJ
Bou-Gharios, G
Chan, J
Kurata, H
Williams, GR
Polak, J
Fisk, NM
Title Intrauterine transplantation of human fetal mesenchymal stem cells from first-trimester blood repairs bone and reduces fractures in osteogenesis imperfecta mice
Journal name Blood   Check publisher's open access policy
ISSN 0006-4971
1528-0020
Publication date 2008-02
Year available 2007
Sub-type Article (original research)
DOI 10.1182/blood-2007-08-105809
Volume 111
Issue 3
Start page 1717
End page 1725
Total pages 9
Place of publication Washington DC., U..S.A.
Publisher American Society of Hematology
Language eng
Subject 1103 Clinical Sciences
Formatted abstract
 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 oimwas 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 ascientific basis for MSC treatment of affected human fetuses.
Keyword Fractures
Osteogenesis Imperfecta
Transplantation
Q-Index Code C1
Q-Index Status Provisional Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Health and Rehabilitation Sciences Publications
 
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