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Pro-Angiogenic and Osteogenic Effects of Adipose Tissue-Derived Pericytes Synergistically Enhanced by Nel-like Protein-1.
- Source :
-
Cells [Cells] 2021 Aug 30; Vol. 10 (9). Date of Electronic Publication: 2021 Aug 30. - Publication Year :
- 2021
-
Abstract
- An important objective of vascularized tissue regeneration is to develop agents for osteonecrosis. We aimed to identify the pro-angiogenic and osteogenic efficacy of adipose tissue-derived (AD) pericytes combined with Nel-like protein-1 (NELL-1) to investigate the therapeutic effects on osteonecrosis. Tube formation and cell migration were assessed to determine the pro-angiogenic efficacy. Vessel formation was evaluated in vivo using the chorioallantoic membrane assay. A mouse model with a 2.5 mm necrotic bone fragment in the femoral shaft was used as a substitute for osteonecrosis in humans. Bone formation was assessed radiographically (plain radiographs, three-dimensional images, and quantitative analyses), and histomorphometric analyses were performed. To identify factors related to the effects of NELL-1, analysis using microarrays, qRT-PCR, and Western blotting was performed. The results for pro-angiogenic efficacy evaluation identified synergistic effects of pericytes and NELL-1 on tube formation, cell migration, and vessel formation. For osteogenic efficacy analysis, the mouse model for osteonecrosis was treated in combination with pericytes and NELL-1, and the results showed maximum bone formation using radiographic images and quantitative analyses, compared with other treatment groups and showed robust bone and vessel formation using histomorphometric analysis. We identified an association between FGF2 and the effects of NELL-1 using array-based analysis. Thus, combinatorial therapy using AD pericytes and NELL-1 may have potential as a novel treatment for osteonecrosis.
- Subjects :
- Adipose Tissue metabolism
Aged
Aged, 80 and over
Animals
Apoptosis
Calcium-Binding Proteins genetics
Cell Movement
Cell Proliferation
Cells, Cultured
Embryo, Mammalian blood supply
Embryo, Mammalian cytology
Embryo, Mammalian metabolism
Female
Humans
Male
Mice
Mice, Inbred NOD
Mice, SCID
Osteonecrosis etiology
Osteonecrosis metabolism
Osteonecrosis pathology
Pericytes metabolism
Adipose Tissue cytology
Calcium-Binding Proteins metabolism
Neovascularization, Physiologic
Osteogenesis
Osteonecrosis therapy
Pericytes cytology
Subjects
Details
- Language :
- English
- ISSN :
- 2073-4409
- Volume :
- 10
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Cells
- Publication Type :
- Academic Journal
- Accession number :
- 34571892
- Full Text :
- https://doi.org/10.3390/cells10092244