Comparative characterization of stem cells from human exfoliated deciduous teeth, dental pulp, and bone marrow–derived mesenchymal stem cells

Kunimatsu, Ryo; Nakajima, Kengo; Awada, Tetsuya; Tsuka, Yuji; Abe, Takaharu; Ando, Kazuyo; Hiraki, Tomoka; Kimura, Aya Hirata; Tanimoto, Kotaro

doi:10.1016/j.bbrc.2018.04.213

Cited by 134 publications

(121 citation statements)

References 25 publications

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“…The bone regeneration ability of SHEDs and DPSCs was comparable to that of hBMSCs (Nakajima et al, ). Further, SHEDs were highly proliferative with up‐regulated bFGF and BMP‐2, compared to that in hBMSCs and hDPSCs, after bone differentiation was induced in vitro (Kunimatsu et al, ). For the in vivo experiment, MSCs were transplanted into the calvaria bone defect.…”

Section: Discussionmentioning

confidence: 99%

Stem cell‐derived conditioned media from human exfoliated deciduous teeth promote bone regeneration

et al. 2020

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Objectives Cleft lip and palate (CL/P) are common congenital orofacial anomalies. Autogenous iliac bone grafting closes alveolar cleft defects but requires surgical intervention. Mesenchymal stem cell culture supernatant can regenerate tissues via paracrine activity. However, little is known about the bone‐regenerative effects of stem cells from human exfoliated deciduous teeth (SHED) and conditioned media (CM). Our aim was to address this. Materials and methods Stem cells were isolated from primary tooth pulp and cultured. Defects were made in calvariae of immunodeficient mice and implanted with stem cell‐ or CM‐containing atelocollagen. Regenerated bone was analysed by microcomputed tomography, haematoxylin–eosin and Masson's trichrome staining. Vascular endothelial growth factor, CD31 and CD34 expression were confirmed by immunohistochemistry, and the presence of several proteins and growth factors was verified in SHED‐CM. Results Bone regeneration was enhanced in defects treated with stem cells and CM compared to that in controls 8 weeks after transplantation. Mature bone formation and angiogenesis were confirmed with CM but not with stem cells or in controls. Secretome analysis using multiple cytokine assays revealed that SHED‐CM contained tissue‐regenerating factors with roles in angiogenesis and osteogenesis. Conclusion CM non‐invasively regenerate bone and might be effective to reconstruct alveolar clefts in CL/P patients.

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Section: Discussionmentioning

confidence: 99%

Stem cell‐derived conditioned media from human exfoliated deciduous teeth promote bone regeneration

et al. 2020

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“…Several studies have observed that stem cells from human exfoliated deciduous teeth (SHED) have signi cantly better and more sustained ability to proliferate and resist senescence than hBMSCs [21,22]. In addition, as the factors secreted by MSCs have a crucial role in maintaining their stemness, we speculate that this may also be true for SHED.…”

Section: Introductionmentioning

confidence: 68%

Hepatocyte growth factor (HGF) and stem cell factor (SCF) maintained the stemness of human bone marrow mesenchymal stem cells (hBMSCs) during long-term expansion by preserving mitochondrial function via the PI3K/AKT, ERK1/2, and STAT3 signaling pathways

Cao

Xie

Liu

et al. 2020

Preprint

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Background: Mesenchymal stem cells (MSCs) have a limited self-renewal ability, impaired multi-differentiation potential, and undetermined cell senescence during in vitro series expansion. To address this concern, we investigated the effects of the microenvironment provided by stem cells from human exfoliated deciduous teeth (SHED) in maintaining the stemness of human bone marrow mesenchymal stem cells (hBMSCs) and identified the key factors and possible mechanisms responsible for maintaining the stemness of MSCs during long-term expansion in vitro.Methods: The passage 3 (P3) to passage 8 (P8) hBMSCs were cultured in the conditioned medium from SHED (SHED-CM). The percentage of senescent cells was evaluated by β-galactosidase staining. In addition, the osteogenic differentiation potential was analyzed by reverse transcription quantitative PCR (RT-qPCR), Western blot, alizarin red and alkaline phosphatase (ALP) staining. Furthermore, RT-qPCR results identified hepatocyte growth factor (HGF) and stem cell factor (SCF) as key factors. Thus, the effects of HGF and SCF on mitochondrial function were assessed by measuring the ROS and mitochondrial membrane potential levels. Finally, selected mitochondrial-related proteins associated with the PI3K/AKT, ERK1/2, and STAT3 signaling pathways were investigated to determine the effects of HGF and SCF in preserving the mitochondrial function of hBMSCs during long-term expansion. Results: SHED-CM had significantly enhanced the cell proliferation, reduced the senescent cells, and maintained the osteogenesis and pro-angiogenic capacity in P8 hBMSCs during long-term expansion. In addition, hBMSCs treated with 100 ng/ml HGF and 10 ng/ml SCF had reduced ROS levels, and preserved mitochondrial membrane potential compared with P8 hBMSCs during long-term expansion. Furthermore, HGF and SCF upregulated the expression of mitochondrial-related proteins associated with the PI3K/AKT, ERK1/2, and STAT3 signaling pathways, possibly contributing to the maintenance of hBMSCs stemness by preserving mitochondrial function. Conclusion: Both HGF and SCF are key factors in maintaining the stemness of hBMSCs by preserving mitochondrial function through the expression of proteins associated with the PI3K/AKT, ERK1/2, and STAT3 signaling pathways. This study provides new insights into the anti-senescence capability of HGF and SCF, as well as new evidence for their potential application in optimizing the long-term culture of MSCs.

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“…Recently, stem cell therapy and tissue engineering have been commonly considered as a great approaches for the treatment of various diseases. Autologous and allogenic bone transplantation is one of the gold standard treatments in bone defect reparation which could be caused by various diseases, infections, congenital defects or trauma [13,14]. Moreover, bone grafting techniques have several limitations and disadvantages, including post-operative pain, infection risk, donor side morbidity, as well as immunological problems, and the search for suitable bone substituents that will mimic the osteogenic potential of autologous bone is needed [15].…”

Section: Discussionmentioning

confidence: 99%

A Comparative In Vitro Analysis of the Osteogenic Potential of Human Dental Pulp Stem Cells Using Various Differentiation Conditions

Okajčeková

Strnádel

Pokusa

et al. 2020

IJMS

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Dental pulp stem cells (DPSCs) have excellent proliferative properties, mineralization potential and can be easily obtained from third molar teeth. Recently, many studies have focused on isolation and differentiation of DPSCs. In our study, we focused on biological properties of non-differentiated DPSCs in comparison with osteogenic differentiated cells from DPSCs. We analyzed morphology as well as mineralization potential using three varied osteogenic differentiation media. After fifteen days of differentiation, calcium deposit production was observed in all three osteogenic differentiation media. However, only one osteogenic medium, without animal serum supplement, showed rapid and strong calcification—OsteoMAX-XF™ Differentiation Medium. Therefore, we examined specific surface markers, and gene and protein expression of cells differentiated in this osteogenic medium, and compared them to non-differentiated DPSCs. We proved a decrease in expression of CD9 and CD90 mesenchymal stem cell surface markers, as well as downregulation in the expression of pluripotency genes (NANOG and OCT-4) and increased levels of expression in osteogenic genes (ALP, BSP, OCN and RUNX2). Moreover, osteogenic proteins, such as BSP and OCN, were only produced in differentiated cells. Our findings confirm that carefully selected differentiation conditions for stem cells are essential for their translation into future clinical applications.

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Comparative characterization of stem cells from human exfoliated deciduous teeth, dental pulp, and bone marrow–derived mesenchymal stem cells

Cited by 134 publications

References 25 publications

Stem cell‐derived conditioned media from human exfoliated deciduous teeth promote bone regeneration

Stem cell‐derived conditioned media from human exfoliated deciduous teeth promote bone regeneration

Hepatocyte growth factor (HGF) and stem cell factor (SCF) maintained the stemness of human bone marrow mesenchymal stem cells (hBMSCs) during long-term expansion by preserving mitochondrial function via the PI3K/AKT, ERK1/2, and STAT3 signaling pathways

A Comparative In Vitro Analysis of the Osteogenic Potential of Human Dental Pulp Stem Cells Using Various Differentiation Conditions

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