FGF2/HGF priming facilitates adipose-derived stem cell-mediated bone formation in osteoporotic defects

Jeong Seop Park; Do Young Kim; Hyun Sook Hong

Heliyon (Jan 2024)

FGF2/HGF priming facilitates adipose-derived stem cell-mediated bone formation in osteoporotic defects

Jeong Seop Park,
Do Young Kim,
Hyun Sook Hong

Affiliations

Jeong Seop Park: Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul, 02447, South Korea
Do Young Kim: Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul, 02447, South Korea
Hyun Sook Hong: Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul, 02447, South Korea; East-West Medical Research Institute, Kyung Hee University, Seoul, 02447, South Korea; Kyung Hee Institute of Regenerative Medicine (KIRM), Medical Science Research Institute, Kyung Hee University Medical Center, Seoul, 02447, South Korea; Corresponding author. Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul, 02447, South Korea.

Journal volume & issue: Vol. 10, no. 2
p. e24554

Abstract

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Aims: The activity of adipose-derived stem cells (ADSCs) is susceptible to the physiological conditions of the donor. Therefore, employing ADSCs from donors of advanced age or with diseases for cell therapy necessitates a strategy to enhance therapeutic efficacy before transplantation. This study aims to investigate the impact of supplementing Fibroblast Growth Factor 2 (FGF2) and Hepatocyte Growth Factor (HGF) on ADSC-mediated osteogenesis under osteoporotic conditions and to explore the underlying mechanisms of action. Main methods: Adipose-derived stem cells (ADSCs) obtained from ovariectomized (OVX) rats were cultured ex vivo. These cells were cultured in an osteogenic medium supplemented with FGF2 and HGF and subsequently autologously transplanted into osteoporotic femur defects using Hydroxyapatite-Tricalcium Phosphate. The assessment of bone formation was conducted four weeks post-transplantation. Key findings: Osteoporosis detrimentally affects the viability and osteogenic differentiation potential of ADSCs, often accompanied by a deficiency in FGF2 and HGF signaling. However, priming with FGF2 and HGF facilitated the formation of immature osteoblasts from OVX ADSCs in vitro, promoting the expression of osteoblastogenic proteins, including Runx-2, osterix, and ALP, during the early phase of osteogenesis. Furthermore, FGF2/HGF priming augmented the levels of VEGF and SDF-1α in the microenvironment of OVX ADSCs under osteogenic induction. Importantly, transplantation of OVX ADSCs primed with FGF2/HGF for 6 days significantly enhanced bone formation compared to non-primed cells. The success of bone regeneration was confirmed by the expression of type-1 collagen and osteocalcin in the bone tissue of the deficient area. Significance: Our findings corroborate that priming with FGF2/HGF can improve the differentiation potential of ADSCs. This could be applied in autologous stem cell therapy for skeletal disease in the geriatric population.

Published in Heliyon

ISSN: 2405-8440 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Science: Science (General); Social Sciences: Social sciences (General)
Website: https://www.cell.com/heliyon/home

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