Humanized culture of periosteal progenitors in allogeneic serum enhances osteogenic differentiation and in vivo bone formation

Roberts, Scott J., Owen, Helen C., Tam, Wai Long, Solie, Lien, Van Cromphaut, Sophie J., Van den Berghe, Greet and Luyten, Frank P. (2014) Humanized culture of periosteal progenitors in allogeneic serum enhances osteogenic differentiation and in vivo bone formation. Stem Cells Translational Medicine, 3 (2). pp. 218-28. ISSN 2157-6564 (doi:10.5966/sctm.2012-0137)

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Abstract

The translation of stem cell-based regenerative solutions from the laboratory to the clinic is often hindered by the culture conditions used to expand cell populations. Although fetal bovine serum (FBS) is widely used, regulatory bodies and safety concerns encourage alternative, xeno-free culturing practices. In an attempt to apply this approach to a bone-forming combination product of human periosteal progenitors (human periosteum derived cells) on a clinically used calcium phosphate carrier, FBS was substituted for human allogeneic serum (hAS) during cell expansion. It was found that cell proliferation was increased in hAS along with an apparent commitment to the osteogenic lineage, indicated by enhanced Runx2 expression, as well as alkaline phosphatase activity and matrix mineralization. Following analysis of signaling pathways, it was found that interferon-mediated signaling was downregulated, whereas JAK-STAT signaling was upregulated. STAT3 phosphorylation was enhanced in hAS-cultured human periosteum derived cells, inhibition of which ablated the proliferative effect of hAS. Furthermore, following in vivo implantation of hAS-cultured cells on NuOss scaffolds, enhanced bone formation was observed compared with FBS (71% increase, p < .001). Interestingly, the de novo-formed bone appeared to have a higher ratio of immature regions to mature regions, indicating that after 8 weeks implantation, tissue-formation processes were continuing. Integration of the implant with the environment appeared to be altered, with a decrease in calcium phosphate grain size and surface area, indicative of accelerated resorption. This study highlights the advantages of using humanized culture conditions for the expansion of human periosteal progenitors intended for bone regeneration.

Item Type: Article
Additional Information: First published online in SCTM on December 27, 2013
Research Areas: A. > School of Science and Technology > Natural Sciences
Item ID: 19100
Useful Links:
Depositing User: Helen Roberts
Date Deposited: 21 Apr 2016 09:59
Last Modified: 11 May 2017 15:55
URI: https://eprints.mdx.ac.uk/id/eprint/19100

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