Validation of human periodontal ligament‐derived cells as a reliable source for cytotherapeutic use

Iwata, Takanori; Yamato, Masayuki; Zhang, Zheng; Mukobata, Shigeki; Washio, Kaoru; Ando, Tomohiro; Feijén, Jan; Okano, Teruo; Ishikawa, Isao

doi:10.1111/j.1600-051x.2010.01597.x

Cited by 182 publications

(171 citation statements)

References 52 publications

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“…Taken together, the results of high periostin expression and a high ALP activity in hPDL cell sheets have confirmed evidence that cell sheets produced in CPC possess PDL properties. Furthermore, these results are consistent with those of experiments conducted on 41 samples of hPDL cells (Iwata et al 2010).…”

Section: Discussionsupporting

confidence: 94%

Assessment of cell sheets derived from human periodontal ligament cells: a pre-clinical study

et al. 2010

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Periodontal-ligament-derived cells (PDL cells) have stem-cell-like properties and, when implanted into periodontal defects in vivo, can induce periodontal regeneration including the formation of new bone, cementum, and periodontal ligament. We have previously demonstrated that PDL cell sheets, harvested from temperature-responsive cell culture dishes, have a great potential for periodontal regeneration. The purpose of this study has been to validate the safety and efficacy of human PDL (hPDL) cell sheets for use in clinical trials. hPDL tissues from three donors were enzymatically digested, and the obtained cells were cultured with media containing autologous serum in a cell-processing center (CPC). The safety and efficacy of hPDL cell sheets were evaluated both in vitro and in vivo. In vitro studies showed that the hPDL cell sheets had high alkaline phosphatase activity and periostin expression (known PDL markers) and no contamination with microorganisms. In vivo studies revealed that hPDL cell sheets, implanted with dentin blocks, induced the formation of cementum and PDL-like tissue in immunodeficient mice. The hPDL cells presented no evidence of malignant transformation. Thus, hPDL cell sheets created in CPCs are safe products and possess the potential to regenerate periodontal tissues.

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Section: Discussionsupporting

confidence: 94%

Assessment of cell sheets derived from human periodontal ligament cells: a pre-clinical study

et al. 2010

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“…In particular, many preclinical and clinical studies have suggested that PDLSCs represent an effective therapeutic tool for periodontal regeneration (Bright et al 2015;Bassir et al 2016). In parallel, methods for PDLSC isolation and production are developing very quickly, from rapid and safe cell propagation/expansion (Iwata et al 2010;Jung et al 2013;Trubiani et al 2015;Wu et al 2016) to optimal cell material production (Wei et al 2012;Gao et al 2013;Iwata et al 2015). Nevertheless, major challenges still exist, particularly challenges related to producing large numbers of cells from clinically limited PDL tissues and manufacturing/banking robust cell materials, ideally in an off-the-shelf format Tang et al 2016;Wu et al 2016).…”

Section: Discussionmentioning

confidence: 99%

“…Along with concerted efforts to produce predictable and reliable approaches to augment bone regeneration in intrabony bone defects, the development of tissue engineering and regenerative medicine has provided new avenues to improve the clinical outcomes of periodontal regeneration using stem cell-based technologies (Chen and Jin 2010;Izumi et al 2011;Chen et al 2012;Lu et al 2013;Monsarrat et al 2014). In this context, stem cells derived from the PDL (PDLSCs) have been demonstrated to be effective in preclinical trials and have been suggested as the best cell type for periodontal tissue regeneration (Iwata et al 2010;Dangaria et al 2011;Tsumanuma et al 2011;Dan et al 2014). Despite several small-scale pilot/feasibility studies that have been performed in humans (Feng et al 2010;Chen et al 2016), the clinical use of PDLSCs for periodontal regeneration still faces numerous challenges (Hynes et al 2012;Lu et al 2013).…”

Section: Introductionmentioning

confidence: 99%

Effects of short-term inflammatory and/or hypoxic pretreatments on periodontal ligament stem cells: in vitro and in vivo studies

et al. 2016

Cell Tissue Res

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In this study, we extensively screened the in vitro and in vivo effects of PDLSCs following short-term inflammatory and/or hypoxic pretreatments. We found that the 24-h hypoxic pretreatment of PDLSCs significantly enhanced cell migration and improved cell surface CXCR4 expression. In addition, hypoxia-pretreated PDLSCs exhibited improved cell colony formation and proliferation. Cells that were dually stimulated also formed more colonies compared to untreated cells but their proliferation did not increase. Importantly, the hypoxic pretreatment of PDLSCs enhanced cell differentiation as determined by elevated RUNX-2 and ALP protein expression. In this context, the inflammatory stimulus impaired cell OCN protein expression, while dual stimuli led to decreased RUNX-2 and OCN mRNA levels. Although preconditioning PDLSCs with inflammatory and/or hypoxic pretreatments resulted in no differences in the production of matrix proteins, hypoxic pretreatment led to the generation of thicker cell sheets; the inflammatory stimulus weakened the ability of cells to form sheets. All the resultant cell sheets exhibited clear bone regeneration following ectopic transplantation as well as in periodontal defect models; the amount of new bone formed by hypoxia-preconditioned cells was significantly greater than that formed by inflammatory stimulus- or dual-stimuli-treated cells or by nonpreconditioned cells. The regeneration of new cementum and periodontal ligaments was only identified in the hypoxia-stimulus and no-stimulus cell groups. Our findings suggest that PDLSCs that undergo short-term hypoxic pretreatment show improved cellular behavior in vitro and enhanced regenerative potential in vivo. The preconditioning of PDLSCs via combined treatments or an inflammatory stimulus requires further investigation.

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“…The differentiation assay was performed as previously described [38]. To study osteogenesis, 1000 cells were plated in a 100-mm culture dish and cultured for 7 days.…”

Section: Differentiation Assaymentioning

confidence: 99%

Multipotent mesenchymal stromal cell sheet therapy for bisphosphonate-related osteonecrosis of the jaw in a rat model

et al. 2016

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Bisphosphonates are frequently used to treat osteoporosis, bone metastasis of various cancers, and other diseases. However, bisphosphonate related-osteonecrosis of the jaw (BRONJ) is an intractable disease because it often recurs after surgery or is exacerbated following conservative treatment. Therefore, an alternative approach for treating BRONJ is needed. In this study, we developed a bone marrow-derived multipotent mesenchymal stromal cell (MSC) sheet to treat BRONJ and investigated the effect of MSC sheet transplantation in a rat model of BRONJ-like disease. The MSC sheet transplantation group showed wound healing in most cases, while only minimal healing was observed in the control group and MSC intravenous injection group. Our results suggest that the MSC sheet is a promising alternative approach for the treatment of BRONJ.

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Validation of human periodontal ligament‐derived cells as a reliable source for cytotherapeutic use

Abstract: A protocol for the successful cultivation and validation of hPDL cells is proposed for clinical settings.

Cited by 182 publications

References 52 publications

Assessment of cell sheets derived from human periodontal ligament cells: a pre-clinical study

Assessment of cell sheets derived from human periodontal ligament cells: a pre-clinical study

Effects of short-term inflammatory and/or hypoxic pretreatments on periodontal ligament stem cells: in vitro and in vivo studies

Multipotent mesenchymal stromal cell sheet therapy for bisphosphonate-related osteonecrosis of the jaw in a rat model

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