Human adipose-derived stem cell spheroids incorporating platelet-derived growth factor (PDGF) and bio-minerals for vascularized bone tissue engineering
- Authors
- Lee, Jinkyu; Lee, Sangmin; Ahmad, Taufiq; Perikamana, Sajeesh Kumar Madhurakkat; Lee, Jinki; Kim, Eun Mi; Shin, Heungsoo
- Issue Date
- Oct-2020
- Publisher
- ELSEVIER SCI LTD
- Keywords
- Fragmented fibers; Spheroid; hADSCs; Stem cell; Angiogenic factor; Bone regeneration
- Citation
- BIOMATERIALS, v.255, pp.1 - 16
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIOMATERIALS
- Volume
- 255
- Start Page
- 1
- End Page
- 16
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/4432
- DOI
- 10.1016/j.biomaterials.2020.120192
- ISSN
- 0142-9612
- Abstract
- Stem cells with mineralized materials have been used for bone regeneration; however, engineering the complex vascularized structure of the natural bone remains a challenge. Here, we developed platelet-derived growth factor (PDGF) and bio-mineral coated fibers which were then assembled with human adipose-derived stem cells (hADSCs) to form spheroids as building blocks for vascularized bone regeneration. The PDGF incorporated within the spheroid increased the proliferation of hADSCs, which was characterized by Ki-67 staining and DNA contents. Furthermore, the PDGF enhanced not only osteogenic differentiation, but also endothelial differentiation of hADSCs; the cells within the spheroids showed significantly greater gene expression by 2.46 +/- 0.14 fold for osteocalcin (OCN) and by 12.85 +/- 3.36 fold for von Willebrand factor (vWF) than those without PDGF. Finally, at two months following transplantation of PDGF-incorporated spheroids onto in vivo mouse calvarial defect, the regenerated bone area (42.48 +/- 10.84%) was significantly enhanced and the greatest number of capillaries and arterioles with indication of transplanted hADSCs were observed. Moreover, millimeter-scale in vitro tissue prepared by fused assembly of the spheroids exhibited greater mRNA expression-associated to endothelial lineage. Taken together, these findings indicate that stem cell spheroids incorporating PDGF and biominerals could be used as a module for successful vascularized bone regeneration.
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