title: Potential of human fetal chorionic stem cells for the treatment of osteogenesis imperfecta.
abstract: Osteogenesis imperfecta (OI) is a genetic bone pathology with prenatal onset, characterized by brittle bones in response to abnormal collagen composition. There is presently no cure for OI. We previously showed that human first trimester fetal blood mesenchymal stem cells (MSCs) transplanted into a murine OI model (oim mice) improved the phenotype. However, the clinical use of fetal MSC is constrained by their limited number and low availability. In contrast, human fetal early chorionic stem cells (e-CSC) can be used without ethical restrictions and isolated in high numbers from the placenta during ongoing pregnancy. Here, we show that intraperitoneal injection of e-CSC in oim neonates reduced fractures, increased bone ductility and bone volume (BV), increased the numbers of hypertrophic chondrocytes, and upregulated endogenous genes involved in endochondral and intramembranous ossification. Exogenous cells preferentially homed to long bone epiphyses, expressed osteoblast genes, and produced collagen COL1A2. Together, our data suggest that exogenous cells decrease bone brittleness and BV by directly differentiating to osteoblasts and indirectly stimulating host chondrogenesis and osteogenesis. In conclusion, the placenta is a practical source of stem cells for the treatment of OI.
authors.affiliation: 1 Institute of Reproductive and Developmental Biology , Imperial College London, London, United Kingdom .
authors.forename: Gemma N
authors.initials: GN
authors.lastname: Jones
authors.forename: Dafni
authors.initials: D
authors.lastname: Moschidou
authors.forename: Hassan
authors.initials: H
authors.lastname: Abdulrazzak
authors.forename: Bhalraj Singh
authors.initials: BS
authors.lastname: Kalirai
authors.forename: Maximilien
authors.initials: M
authors.lastname: Vanleene
authors.forename: Suchaya
authors.initials: S
authors.lastname: Osatis
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Shefelbine
authors.forename: Nicole J
authors.initials: NJ
authors.lastname: Horwood
authors.forename: Massimo
authors.initials: M
authors.lastname: Marenzana
authors.forename: Paolo
authors.initials: P
authors.lastname: De Coppi
authors.forename: J H Duncan
authors.initials: JH
authors.lastname: Bassett
authors.forename: Graham R
authors.initials: GR
authors.lastname: Williams
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Fisk
authors.forename: Pascale V
authors.initials: PV
authors.lastname: Guillot
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000002:abnormalities / Q000378:metabolism; D064987:Cell- and Tissue-Based Therapy; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D020219:Chondrogenesis; D002823:Chorion / Q000166:cytology* / Q000378:metabolism; D024042:Collagen Type I / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D053686:Fetal Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation*; D005333:Fetus; D050723:Fractures, Bone / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D015870:Gene Expression; D006801:Humans; D007274:Injections, Intraperitoneal; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010013:Osteogenesis Imperfecta / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D010920:Placenta / Q000166:cytology* / Q000378:metabolism; D011247:Pregnancy; D033581:Stem Cell Transplantation; D014183:Transplantation, Heterologous
chemical_list: D024042:Collagen Type I
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