Effect of Gelatin on Osteogenic Cell Sheet Formation Using Canine Adipose-Derived Mesenchymal Stem Cells

Kim, Ah Young; Kim, Yongsun; Lee, Jun Young; Yoon, Yongseok; Kim, Wan Hee; Kweon, Oh‐Kyeong

doi:10.3727/096368916x693338

Cited by 56 publications

(52 citation statements)

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“…The properties of cell sheets from various cell sources have been analyzed previously regarding bone regeneration [ 22 , 23 ]. Because cell sheets are flexible and simple to transplantation, cell-sheet technology may replace conventional bone graft methods in the future.…”

Section: Discussionmentioning

confidence: 99%

Bone regeneration by human dental pulp stem cells using a helioxanthin derivative and cell-sheet technology

et al. 2018

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BackgroundHuman dental pulp stem cells (DPSCs), which have the ability to differentiate into multiple lineages, were recently identified. DPSCs can be collected readily from extracted teeth and are now considered to be a type of mesenchymal stem cell with higher clonogenic and proliferative potential than bone marrow stem cells (BMSCs). Meanwhile, the treatment of severe bone defects, such as fractures, cancers, and congenital abnormalities, remains a great challenge, and novel bone regenerative techniques are highly anticipated. Several studies have previously shown that 4-(4-methoxyphenyl)pyrido[40,30:4,5]thieno[2,3-b]pyridine-2-carboxamide (TH), a helioxanthin derivative, induces osteogenic differentiation of preosteoblastic and mesenchymal cells. However, the osteogenic differentiation activities of TH have only been confirmed in some mouse cell lines. Therefore, in this study, toward the clinical use of TH in humans, we analyzed the effect of TH on the osteogenic differentiation of DPSCs, and the in-vivo osteogenesis ability of TH-induced DPSCs, taking advantage of the simple transplantation system using cell-sheet technology.MethodsDPSCs were obtained from dental pulp of the wisdom teeth of five healthy patients (18–22 years old) and cultured in regular medium and osteogenic medium with or without TH. To evaluate osteogenesis of TH-induced DPSCs in vivo, we transplanted DPSC sheets into mouse calvaria defects.ResultsWe demonstrated that osteogenic conditions with TH induce the osteogenic differentiation of DPSCs more efficiently than those without TH and those with bone morphogenetic protein-2. However, regular medium with TH did not induce the osteogenic differentiation of DPSCs. TH induced osteogenesis in both DPSCs and BMSCs, although the gene expression pattern in DPSCs differed from that in BMSCs up to 14 days after induction with TH. Furthermore, we succeeded in bone regeneration in vivo using DPSC sheets with TH treatment, without using any scaffolds or growth factors.ConclusionsOur results demonstrate that TH-induced DPSCs are a useful cell source for bone regenerative medicine, and the transplantation of DPSC sheets treated with TH is a convenient scaffold-free method of bone healing.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-0783-7) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Bone regeneration by human dental pulp stem cells using a helioxanthin derivative and cell-sheet technology

et al. 2018

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“…It is noteworthy that gel is an indispensable material for tissue engineering applications . Both col and gel substrates have excellent osteogenic characteristics and can be used to afford the drawbacks of ionically cross‐linked alg gels …”

Section: Introductionmentioning

confidence: 99%

Collagen‐alginate‐nano‐silica microspheres improved the osteogenic potential of human osteoblast‐like MG‐63 cells

Khatami

Khoshfetrat

Khaksar

et al. 2019

J of Cellular Biochemistry

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Modular bone tissue engineering is touted as an alternative approach to replace the damaged bone tissue. Hydrogel microcapsules could promote therapeutic properties by providing 3D condition and an increased cell‐to‐cell interaction. We investigated the osteogenic properties of alginate‐nano‐silica hydrogels enriched with collagen and gelatin on human osteoblast‐like MG‐63 cells. For encapsulation, cells were divided into three groups; control (alginate+ nano‐silica), collagen (alginate + collagen + nano‐silica), and gelatin (alginate + gelatin + nano‐silica) and expanded for 28 days. Cell survival was determined by trypan blue staining and 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay. To confirm the osteogenic potential, we measured the alkaline phosphatase activity. Alizarin red S staining was used to reveal the existence of hydroxyapatite and transcription BMP‐2, osteocalcin and osteonectin evaluated by the real‐time polymerase chain reaction. Collagen substrate caused a reduced swelling ratio compared with the control and gelatin groups (P < 0.05). Compared with other groups, collagen had potential to improve mechanical strength and generate porous membrane structure. The addition of collagen (4‐fold) and gelatin (1.5‐fold) increased cell proliferation rate compared with the control (P < 0.05). Biochemical analysis and Alizarin red S staining showed that collagen‐induced osteogenesis by induction of alkaline phosphatase and matrix mineralization. The expression of osteocalcin and BMP‐2 was increased in cells from the collagen group. As a result, the combination of natural polymers collagen and gelatin with alginate + nano‐silica can increase the osteogenic potential of human osteoblasts.

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“…In the present study, elevated expression of VEGF in GMSCs might be influenced by the RGD peptide. In a similar study, the application of gelatin in osteogenic cell sheets induced the proliferation of osteoblasts, which was also attributed to the activation of the wnt/β-catenin pathway (Kim et al, 2017). In the present study, Ad-MSCs incubated with gelatin concentrations of 1%, 2%, and 4% had a lower proliferation rate, which might be due to alterations in the optimal medium composition required for the growth of Ad-MSCs.…”

Section: Discussionmentioning

confidence: 52%

“…Osteogenic cell sheets incorporating gelatin had upregulated expression of osteogenic markers such as BMP-7, TGF-β, AP, osteocalcin, and osteopontin in osteogenically differentiated Ad-MSCs (Kim et al, 2017). Similarly, virally transfected BMP-7-overexpressing MSCs had rapid osteogenic differentiation (Xue et al, 2015), which induced bone regeneration in critical-size bone defects in rats (Kargozar et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Gelatin positively regulates the immunosuppressive capabilitiesof adipose-derived mesenchymal stem cells

et al. 2017

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IntroductionAdipose-derived mesenchymal stem cells (Ad-MSCs) are highly multipotent cells with a high potential for differentiation into multiple cell types (Vieira et al., 2010;Park et al., 2012;Mellor et al., 2015). Ad-MSCs produce various growth factors that contribute to injury healing and tissue regeneration (Salgado et al., 2010). The antiinflammatory, immunomodulatory, and antioxidant properties of mesenchymal stem cells (MSCs) make them desirable candidates for cell-based therapies (Soleymaninejadian et al., 2012).The usefulness of MSCs has been selectively enhanced by either manipulating the culture media composition (Langenbach and Handschel, 2013) or by gene transduction (Liu et al., 2015). Pretreatment with proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), and interleukin-6 (IL-6), enhances the immunosuppressive capacity of MSCs by upregulating the expression of indoleamine-2,3-dioxygenase (IDO), which inhibits the proliferation of lymphocytes (Hoogduijn et al., 2010). Gelatin sponges incorporating high amounts of β-tricalcium phosphate (β TCP) have been used to stimulate rat bone marrow MSC proliferation and osteogenic differentiation by stimulating higher alkaline phosphatase (AP) activity and osteocalcin expression (Takahashi et al., 2005). Similarly, a scaffold prepared by mixing chitosan with gelatin, β TCP, and hydroxyapatite (HA) has also been used to induce MSC adhesion, differentiation, and proliferation (Zhao et al., 2006).MSCs cultured in a hyperoxic environment have enhanced viability and paracrine therapeutic capabilities (Song et al., 2010), as well as increased expression of the naturally occurring antioxidant stanniocalcin-1 (SC-1), which prevents oxygen-induced bronchopulmonary dysplasia in rats (Waszak et al., 2012). HO-1, a potent antioxidant enzyme, can be induced in undifferentiated MSCs treated with hemin, which renders the MSCs more resistant to oxidative injury (Barbagallo et al., 2008). Osteogenic growth peptide (OGP) induces HO-1 expression in human bone marrow MSCs, which induces osteogenic differentiation as evidenced by elevated levels of bone morphogenic protein-2 (BMP-2) and osteonectin (Vanella et al., 2010(Vanella et al., , 2013. We have previously reported that gelatin-induced osteogenic cell sheets had active cell proliferation with abundant extracellular matrix and upregulation of osteogenic markers (Kim et al., 2016). In the present study, we evaluated the effects of gelatin on

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Effect of Gelatin on Osteogenic Cell Sheet Formation Using Canine Adipose-Derived Mesenchymal Stem Cells

Cited by 56 publications

References 41 publications

Bone regeneration by human dental pulp stem cells using a helioxanthin derivative and cell-sheet technology

Bone regeneration by human dental pulp stem cells using a helioxanthin derivative and cell-sheet technology

Collagen‐alginate‐nano‐silica microspheres improved the osteogenic potential of human osteoblast‐like MG‐63 cells

Gelatin positively regulates the immunosuppressive capabilitiesof adipose-derived mesenchymal stem cells

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