BMP4-regulated human dental pulp stromal cells promote pulp-like tissue regeneration in a decellularized dental pulp matrix scaffold

Tan, Qin; Cao, Yongguo; Zheng, Xiaowei; Peng, Mengtian; Huang, Enyi; Wang, Jinhua

doi:10.1007/s10266-021-00620-5

Cited by 15 publications

(19 citation statements)

References 28 publications

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“…Of interest, BMP4 was least expressed in DPSCs on soft substrates and showed a stronger mRNA expression on stiffer substrates (15 kPa and 28 kPa). These results are in line with an osteogenic/odontogenic differentiation as promoted by BMP4 [ 78 ]. Consequently, hard tissue formation of DPSCs is promoted by rather stiff substrates [ 31 , 54 ].…”

Section: Discussionsupporting

confidence: 79%

Biomechanical Modulation of Dental Pulp Stem Cell (DPSC) Properties for Soft Tissue Engineering

et al. 2023

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Dental pulp regeneration strategies frequently result in hard tissue formation and pulp obliteration. The aim of this study was to investigate whether dental pulp stem cells (DPSCs) can be directed toward soft tissue differentiation by extracellular elasticity. STRO-1-positive human dental pulp cells were magnetically enriched and cultured on substrates with elasticities of 1.5, 15, and 28 kPa. The morphology of DPSCs was assessed visually. Proteins relevant in mechanobiology ACTB, ITGB1, FAK, p-FAK, TALIN, VINCULIN, PAXILLIN, ERK 1/2, and p-ERK 1/2 were detected by immunofluorescence imaging. Transcription of the pulp marker genes BMP2, BMP4, MMP2, MMP3, MMP13, FN1, and IGF2 as well as the cytokines ANGPT1, VEGF, CCL2, TGFB1, IL2, ANG, and CSF1 was determined using qPCR. A low stiffness, i.e., 1.5 kPa, resulted in a soft tissue-like phenotype and gene expression, whereas DPSCs on 28 kPa substrates exhibited a differentiation signature resembling hard tissues with a low cytokine expression. Conversely, the highest cytokine expression was observed in cells cultured on intermediate elasticity, i.e., 15 kPa, substrates possibly allowing the cells to act as “trophic mediators”. Our observations highlight the impact of biophysical cues for DPSC fate and enable the design of scaffold materials for clinical pulp regeneration that prevent hard tissue formation.

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Section: Discussionsupporting

confidence: 79%

Biomechanical Modulation of Dental Pulp Stem Cell (DPSC) Properties for Soft Tissue Engineering

et al. 2023

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“…Different animal models were used in the included studies. The majority used mice [ 38 , 39 , 41 , 42 , 45 , 46 , 48 , 50 , 51 , 53 ] followed by rats [ 43 , 44 , 49 , 52 ], pigs [ 39 , 40 ] and beagle dogs [ 23 , 47 ]. The main source of ECM used was swine [ 23 , 39 , 41 , 47 , 53 ], human [ 46 , 48 , 50 ] or bovine dental pulp [ 43 – 45 ].…”

Section: Resultsmentioning

confidence: 99%

“…The majority used mice [ 38 , 39 , 41 , 42 , 45 , 46 , 48 , 50 , 51 , 53 ] followed by rats [ 43 , 44 , 49 , 52 ], pigs [ 39 , 40 ] and beagle dogs [ 23 , 47 ]. The main source of ECM used was swine [ 23 , 39 , 41 , 47 , 53 ], human [ 46 , 48 , 50 ] or bovine dental pulp [ 43 – 45 ]. Others used cell-generated ECM [ 38 , 42 ], swine tooth bud [ 40 ], human amniotic membrane [ 49 , 52 ] and rats’ submandibular glands [ 51 ].…”

Section: Resultsmentioning

confidence: 99%

Influence of extracellular matrix scaffolds on histological outcomes of regenerative endodontics in experimental animal models: a systematic review

Elnawam,

Abdallah,

Nouh

et al. 2024

BMC Oral Health

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Background Decellularized extracellular matrix (dECM) from several tissue sources has been proposed as a promising alternative to conventional scaffolds used in regenerative endodontic procedures (REPs). This systematic review aimed to evaluate the histological outcomes of studies utilizing dECM-derived scaffolds for REPs and to analyse the contributing factors that might influence the nature of regenerated tissues. Methods The PRISMA 2020 guidelines were used. A search of articles published until April 2024 was conducted in Google Scholar, Scopus, PubMed and Web of Science databases. Additional records were manually searched in major endodontic journals. Original articles including histological results of dECM in REPs and in-vivo studies were included while reviews, in-vitro studies and clinical trials were excluded. The quality assessment of the included studies was analysed using the ARRIVE guidelines. Risk of Bias assessment was done using the (SYRCLE) risk of bias tool. Results Out of the 387 studies obtained, 17 studies were included for analysis. In most studies, when used as scaffolds with or without exogenous cells, dECM showed the potential to enhance angiogenesis, dentinogenesis and to regenerate pulp-like and dentin-like tissues. However, the included studies showed heterogeneity of decellularization methods, animal models, scaffold source, form and delivery, as well as high risk of bias and average quality of evidence. Discussion Decellularized ECM-derived scaffolds could offer a potential off-the-shelf scaffold for dentin-pulp regeneration in REPs. However, due to the methodological heterogeneity and the average quality of the studies included in this review, the overall effectiveness of decellularized ECM-derived scaffolds is still unclear. More standardized preclinical research is needed as well as well-constructed clinical trials to prove the efficacy of these scaffolds for clinical translation. Other The protocol was registered in PROSPERO database #CRD42023433026. This review was funded by the Science, Technology and Innovation Funding Authority (STDF) under grant number (44426).

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“…Conditioned medium made from decellularized scaffolds can ameliorate the proliferation and migration ability of DPSCs, and the animal model of dental pulp regeneration demonstrates ideal results [ 51 , 54 , 55 , 56 , 57 ]. Decellularized pulp matrix also enhanced the odontogenic differentiation ability of DPSCs with high BMP4 expression with the help of recombinant adenovirus [ 58 ]. Considering the loss of extracellular matrix components during the acellular process, some researchers modified the decellularized dental pulp matrix materials with laminin, a kind of extracellular matrix protein, which exhibits more advantages in odontogenic differentiation [ 59 ].…”

Section: Strategiesmentioning

confidence: 99%

Creating a Microenvironment to Give Wings to Dental Pulp Regeneration—Bioactive Scaffolds

Jiang

et al. 2023

Pharmaceutics

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Dental pulp and periapical diseases make patients suffer from acute pain and economic loss. Although root canal therapies, as demonstrated through evidence-based medicine, can relieve symptoms and are commonly employed by dentists, it is still difficult to fully restore a dental pulp’s nutrition, sensory, and immune-regulation functions. In recent years, researchers have made significant progress in tissue engineering to regenerate dental pulp in a desired microenvironment. With breakthroughs in regenerative medicine and material science, bioactive scaffolds play a pivotal role in creating a suitable microenvironment for cell survival, proliferation, and differentiation, following dental restoration and regeneration. This article focuses on current challenges and novel perspectives about bioactive scaffolds in creating a microenvironment to promote dental pulp regeneration. We hope our readers will gain a deeper understanding and new inspiration of dental pulp regeneration through our summary.

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BMP4-regulated human dental pulp stromal cells promote pulp-like tissue regeneration in a decellularized dental pulp matrix scaffold

Cited by 15 publications

References 28 publications

Biomechanical Modulation of Dental Pulp Stem Cell (DPSC) Properties for Soft Tissue Engineering

Biomechanical Modulation of Dental Pulp Stem Cell (DPSC) Properties for Soft Tissue Engineering

Influence of extracellular matrix scaffolds on histological outcomes of regenerative endodontics in experimental animal models: a systematic review

Creating a Microenvironment to Give Wings to Dental Pulp Regeneration—Bioactive Scaffolds

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