Mapping human serum induced gene networks as a basis for the creation of biomimetic periosteum for bone repair
Article
Al Hosni, R., Shah, M., Cheema, U., Roberts, H., Luyten, F. and Roberts, S. 2020. Mapping human serum induced gene networks as a basis for the creation of biomimetic periosteum for bone repair. Cytotherapy. 22 (8), pp. 424-435.
| Type | Article |
|---|---|
| Title | Mapping human serum induced gene networks as a basis for the creation of biomimetic periosteum for bone repair |
| Authors | Al Hosni, R., Shah, M., Cheema, U., Roberts, H., Luyten, F. and Roberts, S. |
| Abstract | The periosteum is a highly vascularised, collagen-rich tissue that plays a crucial role in directing bone repair. This is orchestrated primarily by its resident progenitor cell population. Indeed, preservation of periosteum integrity is critical for bone healing. Cells extracted from the periosteum retain their osteochondrogenic properties and as such are a promising basis for tissue engineering strategies for the repair of bone defects. However, the culture expansion conditions, and the way in which the cells are reintroduced to the defect site are critical aspects of successful translation. Indeed, expansion in human serum and implantation on biomimetic materials has previously been shown to improve in vivo bone formation. As such, this study aimed to develop a protocol to allow for the expansion of human periosteum derived cells (hPDCs) in a biomimetic periosteal-like environment. The expansion conditions were defined through the investigation of the bioactive cues involved in augmenting hPDC proliferative and multipotency characteristics, based on transcriptomic analysis of cells cultured in human serum. Master regulators of transcriptional networks were identified and an optimised periosteal derived-growth factor cocktail (PD-GFC; containing β-Estradiol, FGF2, TNFα, TGFβ, IGF-1 and PDGF-BB) was generated. Expansion of hPDCs in PD-GFC resulted in serum mimicry with regards to the cell morphology, proliferative capacity and chondrogenic differentiation. When incorporated into a 3D collagen-type-1 matrix and cultured in PD-GFC, the hPDCs migrated to the surface that represented the matrix topography of the periosteum cambium layer. Furthermore, gene expression analysis revealed a downregulated Wnt and TGFβ signature and an upregulation of CREB, which may indicate the hPDCs are recreating their progenitor cell signature. This study highlights the first stage in the development of a biomimetic periosteum which may have applications in bone repair. |
| Keywords | periosteum; bone defect; periosteal cells ; transcriptomics; cell potency |
| Publisher | Elsevier |
| Journal | Cytotherapy |
| ISSN | 1465-3249 |
| Electronic | 1477-2566 |
| Publication dates | |
| Online | 07 Jun 2020 |
| 01 Aug 2020 | |
| Publication process dates | |
| Deposited | 31 Mar 2020 |
| Submitted | 05 Dec 2019 |
| Accepted | 23 Mar 2020 |
| Output status | Published |
| Accepted author manuscript | License |
| Copyright Statement | © 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license. |
| Web address (URL) | https://doi.org/10.1016/j.jcyt.2020.03.434 |
| Web of Science identifier | WOS:000550737200004 |
| Language | English |
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