Origin of bone-forming cells in human osteosarcomas transplanted into nude mice—which cells produce bone, human or mouse?

In this study, we investigated a clinically relevant model of in vivo ectopic bone formation utilizing human periosteum derived cells (HPDCs) seeded in a Collagraft™ carrier and explored the mechanisms by which this process is driven. Bone formation occurred after eight weeks when a minimum of one million HPDCs was loaded on Collagraft™ carriers and implanted subcutaneously in NMRI nu/nu mice. De novo bone matrix, mainly secreted by the HPDCs, was found juxta-proximal of the calcium phosphate (CaP) granules suggesting that CaP may have triggered the ‘osteoinductive program’. Indeed, removal of the CaP granules by ethylenediaminetetraacetic acid decalcification prior to cell seeding and implantation resulted in loss of bone formation. In addition, inhibition of endogenous bone morphogenetic protein and Wnt signalling by overexpression of the secreted antagonists Noggin and Frzb, respectively, also abrogated osteoinduction. Proliferation of the engrafted HPDCs was strongly reduced in the decalcified scaffolds or when seeded with adenovirus-Noggin/Frzb transduced HPDCs indicating that cell division of the engrafted HPDCs is required for the direct bone formation cascade. These data suggest that this model of bone formation is similar to that observed during physiological intramembranous bone development and may be of importance when investigating tissue engineering strategies.

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“…The probes for human specific and mouse specific Alu were prepared by PCR [12, 33]. ISH was performed as described previously [34].…”

Section: Methodsmentioning

confidence: 99%

A clinically relevant model of osteoinduction: a process requiring calcium phosphate and BMP/Wnt signalling

Eyckmans

Roberts

Schrooten

et al. 2010

J Cellular Molecular Medi

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“…In situ hybridization for mL1 sequences was carried out with a digoxigenin (DIG)-labeled, 416 bp antisense DNA probe corresponding to the consensus sequence of mouse mL1 (Hatano et al, 1998). Probe labeling was performed by PCR with the PCR DIG Probe Synthesis Kit (Roche, Mannheim, Germany).…”

Section: In Situ Hybridizationmentioning

confidence: 99%

BMP-2-dependent integration of adult mouse subventricular stem cells into the neural crest of chick and quail embryos

Busch¹,

Oppitz²,

Sailer³

et al. 2006

Journal of Cell Science

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Central nervous system (CNS) stem cells isolated from the subventricular zone (SVZ) show a remarkable differentiation potential into neural derivatives. Surprisingly adult SVZ cells can also be induced in vitro to differentiate into neural crest cell fates. This fate switch is dependent on the combination of fibroblast growth factor 2 (FGF2) and bone morphogenetic proteins (BMPs). Here we transplanted adult SVZ stem cells from GFP mice as neurospheres into the trunk neural tube of chick and quail embryos. Only neurospheres pre-exposed to BMP-2 and FGF2 formed close contacts with the dorsal neuroepithelium corresponding to the neural crest area. GFP-positive cells emigrated from the neurosphere and were identified in the roof plate, the dorsal neuroepithelium and among emigrating neural crest cells adjacent to the neural tube. Neurospheres not treated with BMP-2 did not integrate into the neuroepithelium. Our data demonstrate that adult CNS stem cells can be efficiently prepared in vitro for integration into the embryonic neural crest. BMP-2 treatment conveys the necessary morphogenetic capabilities to adult stem cells for future clinical transplantation strategies.

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“…Digoxigenin was detected using a commercially available kit (DIG Nucleic Acid Detection kit; Roche Molecular Biochemicals) according to the manufacturer's protocol. DIG-labeled mouse-specific L1 probe was obtained as described previously (25). In situ hybridization for m-specific L1 repeats was carried out as described above for human ALU repeats, with a few modifications.…”

Section: Genesmentioning

confidence: 99%

Molecular markers predictive of the capacity of expanded human articular chondrocytes to form stable cartilage in vivo

Dell’Accio¹,

Bari²,

Luyten³

2001

Arthritis & Rheumatism

301

217

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Origin of bone-forming cells in human osteosarcomas transplanted into nude mice—which cells produce bone, human or mouse?

Cited by 23 publications

References 19 publications

A clinically relevant model of osteoinduction: a process requiring calcium phosphate and BMP/Wnt signalling

A clinically relevant model of osteoinduction: a process requiring calcium phosphate and BMP/Wnt signalling

BMP-2-dependent integration of adult mouse subventricular stem cells into the neural crest of chick and quail embryos

Molecular markers predictive of the capacity of expanded human articular chondrocytes to form stable cartilage in vivo

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