Human adipose-derived stem cells and simvastatin-functionalized biomimetic calcium phosphate to construct a novel tissue-engineered bone

Zhang, Xiao; Jiang, Weiran; Liu, Yunsong; Zhang, Ping; Wang, Linchuan; Li, Wenyue; Wu, Gang; Ge, Yajun

doi:10.1016/j.bbrc.2017.11.150

Cited by 12 publications

(14 citation statements)

References 19 publications

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“…At each point of investigation the present study revealed significant decreases ( p < 0.01) of the groups with 1.0 and 2.0 µM SV compared to all other groups. On the contrary, a significant increase of ALP within studies investigating SV impregnated scaffolds regarding the effect of SV determined at day 7 and 14, respectively [6,7,28], but only one of them investigated hADSC [28]. Previous findings shows observation periods up to 14 days so a comparison to the present results with an observation period of 28 days in the present study is limited [5][6][7]28].…”

Section: Discussioncontrasting

confidence: 63%

“…The investigated effects of SV upon mineralizing cells like induced hADSC can be defined as pleiotropic effects of SV. When the results of the current study were combined with the findings of other studies [5][6][7]28], hADSC appear to be a promising source of cells that can be used as the basis for a potential bone graft substitute. royalsocietypublishing.org/journal/rsob Open Biol.…”

Section: Discussionmentioning

confidence: 58%

“…In previous studies mineralization potential [6,27], expression of osteogenic markers on gene and protein level [10,14,27] and osteoblastic differentiation and proliferation [9,14,27] were investigated under influence of SV. The used human cells were, for instance, obtained from tissues like bone marrow and mesenchymal stem cells [14], periodontal ligament [10,27], odontoblast-like cells [11], cells from adipose tissues [5,28] and osteoblasts from bone chips [8]. The used SV concentrations in animal studies of rodent origin [6,7,[15][16][17][18][19][20][29][30][31][32][33] were quiet equal.…”

Section: Discussionmentioning

confidence: 99%

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Pleiotropic effects on proliferation and mineralization of primary human adipose tissue-derived stromal cells induced by simvastatin

et al. 2022

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The circulating low-density lipoprotein concentration in blood can be reduced by the administration of statins. Frequently simvastatin (SV) is prescribed. Due to the reported pleiotropic effects of SV the aim of this study was to evaluate mineralization effects on human adipose tissue-derived stromal cells upon administration of SV. After informed consent human adipose tissue-derived stromal cells were obtained from tissue surplus of regular treatments of 14 individuals. According to established protocols after adding various SV concentrations (0.01 µM, 0.1 µM, 1.0 µM, 2.0 µM), alkaline phosphate (osteoblastic marker), mineralization capability and viability were determined at day 18, 21 and 28. The Kruskal–Wallis test was performed for statistical analysis. After adding SV a dose-dependent significant decreased viability and levels of alkaline phosphatase ( p < 0.01) and a significantly increased mineralization ( p < 0.01) of the primary cultures was recognized during the late mineralization stage. Mineralization of the human adipose tissue-derived stromal cells was induced by SV, possibly originated from alternative pathways than the alkaline phosphatase pathway. Further investigations should be performed regarding switching into the osteoblastic differentiation and as a possible source of cells that can be used as the basis for a potential bone graft substitute, which may allow an extension of the field of application.

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Section: Discussioncontrasting

confidence: 63%

Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

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Pleiotropic effects on proliferation and mineralization of primary human adipose tissue-derived stromal cells induced by simvastatin

et al. 2022

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“…Cell-based bone tissue engineering is an interdisciplinary technology that combines stem cells and technologies in material engineering and bioactive reagents with the ultimate goal of regenerating bone tissues in LVBD 14,33,34. For hASC-based tissue-engineered bone, the application of bioactive agents to efficaciously induce the osteoblastogenic differentiation of hASCs is pivotal for the success of this technique.…”

Section: Discussionmentioning

confidence: 99%

<p>Epigallocatechin-3-gallate enhances the osteoblastogenic differentiation of human adipose-derived stem cells</p>

Zhang¹,

Wu²,

Xu³

et al. 2019

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Purpose The aim of this study is to investigate the effects of epigallocatechin-3-gallate (EGCG), a major polyphenol extracted from green tea, on the osteoblastogenic differentiation of human adipose-derived stem cells (hASCs). Patients and methods hASCs were acquired from human adipose tissue. With informed consent, subcutaneous adipose tissue samples were harvested from periorbital fat pad resections from ten healthy female adults who underwent double eyelid surgery. hASCs were cultured in osteogenic medium with or without EGCG (1 μM, 5 μM, or 10 μM) for 14 days. We evaluated the effects of EGCG by quantifying cell growth, ALP activity (an early osteoblastogenic differentiation marker), BSP, OCN (a late osteoblastogenic differentiation marker), and extracellular matrix mineralization. We also performed Western blots to measure osteoblastogenesis-related proteins such as Runx2 and adipoblastogenesis-related transcription factors, such as STAT3, C/EBP-α, and PPAR-γ. Results EGCG at 5 μM resulted in significantly higher cell proliferation and ALP activity than did the control on days 3, 7, and 14. On day 7, 5 μM EGCG significantly enhanced BSP expression. On day 14, EGCG at all concentrations promoted OCN expression. In addition, EGCG at 5 μM resulted in the highest level of extracellular matrix mineralization. On day 3, the expression levels of Runx2 were significantly higher in the 5 μM EGCG group than in the other groups, whereas later, on days 7 and 14, Runx2 expression levels in the EGCG group were significantly lower than those of the control group. EGCG at all three concentrations was associated with significantly lower levels of phosphorylated STAT3, C/EBP-α, and PPAR-γ. Conclusion EGCG at 5 μM significantly enhanced the osteoblastogenic differentiation of hASCs.

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“…In addition, sustained release of proteins or growth factors within the therapeutic range can be achieved by incorporating therapeutic agents into the coating (37)(38)(39)(40)(41). A gradual long-term release of simvastatin was also achieved by the incorporation of the drug in bCaP coating (42)(43)(44).…”

Section: Introductionmentioning

confidence: 99%

Controlled M1-to-M2 transition of aged macrophages by calcium phosphate coatings

et al. 2019

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Older adults suffer from weakened and delayed bone healing due to age-related alterations in bone cells and in the immune system. Given the interaction between the immune system and skeletal cells, therapies that address deficiencies in both the skeletal and the immune system are required to effectively treat bone injuries of older patients. The sequence of macrophage activation observed in healthy tissue repair involves a transition from a pro-inflammatory state followed by a pro-reparative state. In older patients, inflammation is slower to resolve and impedes healing. The goal of this study was to design a novel drug delivery system for temporal guidance of the polarization of macrophages using bone grafting materials. A biomimetic calcium phosphate coating (bCaP) physically and temporally separated the pro-inflammatory stimulus interferon-gamma (IFNγ) from the pro-reparative stimulus simvastatin (SIMV). Effective doses were identified using a human monocyte line (THP-1) and testing culminated with bone marrow macrophages obtained from old mice. Sequential M1-to-M2 activation was achieved with both cell types. These results suggest that this novel immunomodulatory drug delivery system holds potential for controlling macrophage activation in bones of older patients.

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Human adipose-derived stem cells and simvastatin-functionalized biomimetic calcium phosphate to construct a novel tissue-engineered bone

Cited by 12 publications

References 19 publications

Pleiotropic effects on proliferation and mineralization of primary human adipose tissue-derived stromal cells induced by simvastatin

Pleiotropic effects on proliferation and mineralization of primary human adipose tissue-derived stromal cells induced by simvastatin

<p>Epigallocatechin-3-gallate enhances the osteoblastogenic differentiation of human adipose-derived stem cells</p>

Controlled M1-to-M2 transition of aged macrophages by calcium phosphate coatings

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