title: Neo-vascularization and bone formation mediated by fetal mesenchymal stem cell tissue-engineered bone grafts in critical-size femoral defects.
abstract: Tissue-engineered bone grafts (TEBG) require highly osteogenic cell sources for use in fracture repair applications. Compared to other sources of mesenchymal stem cells (MSC), human fetal MSC (hfMSC) have recently been shown to be more proliferative and osteogenic. We studied the functional performance of hfMSC-mediated TEBG in 7 mm rat femoral critical-sized bone defects (CSD). Dynamically-cultured and osteogenically-primed hfMSC seeded onto macroporous poly-epsilon-caprolactone tri-calcium phosphate scaffolds were transplanted into CSDs. After 12 weeks, hfMSC-mediated TEBG induced 2.1x more new bone formation (43.3+/-10.5 vs. 21.0+/-7.4 mm(3), p<0.05), with greater compact and woven bone, and a 9.8x increase in stiffness (3.9+/-1.7 vs. 0.4+/-0.3 mNm/degree, p<0.05) compared to acellular scaffolds, such that only animals transplanted with TEBG underwent full fracture repair of the CSD. Although hfMSC survived for <4 weeks, by 4 weeks they were associated with a 3.9x larger vasculature network in the defect area (35.2+/-11.1 vs. 6.5+/-3.6 mm(3)p<0.05), suggesting an important role for hfMSC in the promotion of neo-vasculogenesis. We speculate that hfMSC-mediated healing of the CSD by stimulating neo-vascularization through as yet undetermined mechanisms. This proof-of-principle study demonstrates the utility of primitive MSC for bone regeneration, and may be of relevance to vascularization in other areas of regenerative medicine.
authors.affiliation: Mechanical Engineering, Faculty of Engineering, National University of Singapore, Singapore.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Zhang
authors.forename: Swee-Hin
authors.initials: SH
authors.lastname: Teoh
authors.forename: Mark S K
authors.initials: MS
authors.lastname: Chong
authors.forename: Eddy S M
authors.initials: ES
authors.lastname: Lee
authors.forename: Lay-Geok
authors.initials: LG
authors.lastname: Tan
authors.forename: Citra N
authors.initials: CN
authors.lastname: Mattar
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Fisk
authors.forename: Mahesh
authors.initials: M
authors.lastname: Choolani
authors.forename: Jerry
authors.initials: J
authors.lastname: Chan
mesh_terms: D000818:Animals; D005269:Femur / Q000098:blood supply*; D005333:Fetus / Q000166:cytology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D018625:Microscopy, Atomic Force; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D023822:Tissue Engineering / Q000379:methods*; D014057:Tomography, X-Ray Computed