Spheroid culture enhances osteogenic potential of periodontal ligament mesenchymal stem cells

Moritani, Yuki; Usui, Michihiko; Sano, Koichi; Nakazawa, Kimitaka; Hanatani, Tomoya; Nakatomi, Mitsushiro; Iwata, Takanori; Sato, Tsuyoshi; Ariyoshi, Wataru; Nishihara, Tatsuji; Nakashima, Keisuke

doi:10.1111/jre.12577

Cited by 45 publications

(57 citation statements)

References 45 publications

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“…Pennock et al demonstrated that spheroid culture of BM‐MSCs resulted in the induction of autophagy, as well as a shift in the mode of energy production from oxidative phosphorylation to anaerobic; the expression of the stem cell genes Oct4 , Nanog , and Sox2 was enhanced to induce the dedifferentiation of cells. Other previous studies have also reported the enhanced gene expression of Oct4 and Sox2 . We obtained data showing the enhancement of these genes; however, we concluded that this enhancement was derived from genomic DNA contamination, and that spheroid culture of PDLSCs did not increase their expression.…”

Section: Discussionmentioning

confidence: 38%

“…However, we did not find the regeneration of periodontal tissues by transplanting of PDLSC spheroids into periodontal defects in rats, although the sample size was small. There have been several reports that demonstrated the enhancement of tissue regeneration by transplantation of spheroids . Possible explanation of a failure of periodontal regeneration in this study maybe the number of dead cells contained in spheroid.…”

Section: Discussionmentioning

confidence: 62%

“…Other previous studies have also reported the enhanced gene expression of Oct4 and Sox2. [28][29][30]32,40,41 We obtained data showing the enhancement of these genes; however, we concluded that this enhancement was derived from genomic DNA contamination, and that spheroid culture of PDLSCs did not increase their expression. It is interesting that all these studies, which showed enhanced gene expression of Oct4-A, Nanog, and Sox2, did not mention about DNase treatment of RNA samples.…”

Section: Discussionmentioning

confidence: 85%

“…Recently, two studies have reported the characteristics of PDLSCs under spheroid culture . There are four big differences among them.…”

Section: Discussionmentioning

confidence: 99%

“…There have been several reports that demonstrated the enhancement of tissue regeneration by transplantation of spheroids. 41 Periodontal defects were created on buccal side of rat first mandibular (2 × 3 mm) and the defects were kept empty (Control) or filled with PDLSC spheres. Lower panels demonstrate the micro-CT images of rat mandibular first molar 4 wks after transplantation.…”

Section: Discussionmentioning

confidence: 99%

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Changes in characteristics of periodontal ligament stem cells in spheroid culture

Iwasaki

Akazawa

Watabe

et al. 2018

J of Periodontal Research

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Objectives The periodontal ligament (PDL) has important roles in maintaining homeostasis, wound healing, and regeneration of periodontal tissues by supplying stem/progenitor cells. Periodontal ligament stem cells (PDLSCs) have mesenchymal stem cell (MSC)‐like characteristics and can be isolated from periodontal tissues. The aim of this study was to examine the effect of three‐dimensional spheroid culture on the characteristics of PDLSCs. Material and Methods Periodontal ligament stem cells were isolated and cultured from healthy teeth, and PDLSC spheroids were formed by pellet culture in polypropylene tubes. The proliferation of PDLSCs in spheroids and conventional two‐dimensional (2D) cultures were examined by immunostaining for Ki67. Cell death and cell size were analyzed using flow cytometry. Gene expression changes were investigated by quantitative real time PCR. Results Periodontal ligament stem cells spontaneously formed spheroid masses in pellet culture. The size of PDLSC spheroids was inversely proportional to the culture period. Fewer Ki67‐positive cells were detected in PDLSC spheroids compared to those in 2D culture. Flow cytometry revealed an increase in dead cells and a decrease in cell size in PDLSC spheroids. The expression levels of genes related to anti‐inflammation (TSG6, COX2, MnSOD) and angiogenesis (VEGF, bFGF, HGF) were drastically increased by spheroid culture compared to 2D culture. TSG6 gene expression was inhibited in PDLSC spheroids in the presence of the apoptosis signal inhibitor, Z‐VAD‐FMK. Additionally, PDLSC spheroid transplantation into rat periodontal defects did not induce the regeneration of periodontal tissues. Conclusions We found that spheroid culture of PDLSCs affected several characteristics of PDLSCs, including the expression of genes related to anti‐inflammation and angiogenesis; apoptosis signaling may be involved in these changes. Our results revealed the characteristics of PDLSCs in spheroid culture and have provided new information to the field of stem cell research.

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Section: Discussionmentioning

confidence: 38%

Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 85%

“…Recently, two studies have reported the characteristics of PDLSCs under spheroid culture . There are four big differences among them.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Changes in characteristics of periodontal ligament stem cells in spheroid culture

Iwasaki

Akazawa

Watabe

et al. 2018

J of Periodontal Research

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Light‐controlled scaffold‐ and serum‐free hard palatal‐derived mesenchymal stem cell aggregates for bone regeneration

Jiang

Shao

et al. 2022

Bioengineering & Transla Med

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Cell aggregates that mimic in vivo cell–cell interactions are promising and powerful tools for tissue engineering. This study isolated a new, easily obtained, population of mesenchymal stem cells (MSCs) from rat hard palates named hard palatal‐derived mesenchymal stem cells (PMSCs). The PMSCs were positive for CD90, CD44, and CD29 and negative for CD34, CD45, and CD146. They exhibited clonogenicity, self‐renewal, migration, and multipotent differentiation capacities. Furthermore, this study fabricated scaffold‐free 3D aggregates using light‐controlled cell sheet technology and a serum‐free method. PMSC aggregates were successfully constructed with good viability. Transplantation of the PMSC aggregates and the PMSC aggregate‐implant complexes significantly enhanced bone formation and implant osseointegration in vivo, respectively. This new cell resource is easy to obtain and provides an alternative strategy for tissue engineering and regenerative medicine.

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Effects of collagen membranes and bone substitute differ in periodontal ligament cell microtissues and monolayers

Janjić

Agis

Moritz

et al. 2021

Journal of Periodontology

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Author contribution statement: KJ contributed to conceptualization of the project and manuscript, performance of experiments, data evaluation and interpretation as well as manuscript writing. HA contributed to conceptualization of the project and manuscript preparation. AM and XRF contributed to data interpretation and manuscript preparation. OA contributed to conceptualization of the project and manuscript, data evaluation and interpretation as well as manuscript preparation.

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Spheroid culture enhances osteogenic potential of periodontal ligament mesenchymal stem cells

Abstract: Spheroid cultures of hPDLMSCs may be a novel and useful tool in regenerative medicine.

Cited by 45 publications

References 45 publications

Changes in characteristics of periodontal ligament stem cells in spheroid culture

Changes in characteristics of periodontal ligament stem cells in spheroid culture

Light‐controlled scaffold‐ and serum‐free hard palatal‐derived mesenchymal stem cell aggregates for bone regeneration

Effects of collagen membranes and bone substitute differ in periodontal ligament cell microtissues and monolayers

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