Translational pathway of scalable, allogenic encapsulated Mesenchymal Stem Cells for Dental Pulp Regeneration. RanoKure a controlled Phase I/II clinical trial designed to evaluate the survival of mature permanent teeth with apical lesion following a regenerative endodontics procedure

Cytotherapy ◽  
2018 ◽  
Vol 20 (5) ◽  
pp. S93-S94
Author(s):  
C. Brizuela ◽  
D. Urrejola ◽  
G. Meza ◽  
I. Angelopoulos ◽  
M. Khoury
Keyword(s):  
Clinical Trial ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Phase I ◽  
Dental Pulp ◽  
Permanent Teeth ◽  
Pulp Regeneration ◽  
Regenerative Endodontics

scholarly journals Pulp Stem Cell–Mediated Functional Pulp Regeneration

2018 ◽  
Vol 98 (1) ◽  
pp. 27-35 ◽  
Author(s):  
B. Sui ◽  
C. Chen ◽  
X. Kou ◽  
B. Li ◽  
K. Xuan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Dental Pulp ◽  
De Novo ◽  
Convincing Evidence ◽  
Permanent Teeth ◽  
Deciduous Teeth ◽  
Pulp Regeneration ◽  
Regenerative Endodontics

The preservation of vital dental pulp with vasculature and nerve components remains one of the most significant challenges in modern dentistry. Due to the immense potential for neurovascularization, mesenchymal stem cell (MSC) transplantation has shown emerging promise in regenerative medicine and dental translational practice. Actually, pulp mesenchymal stem cells, including postnatal dental pulp stem cells (from permanent teeth) and stem cells from human exfoliated deciduous teeth, possess unique properties based on their origins from neural crest or glial cells. Furthermore, they reside in a neurovascular niche and have the potential for neurogenesis, angiogenesis, and neurovascular inductive activity. According to current pulp regeneration strategies, pulp stem cell–mediated approaches to regeneration have demonstrated convincing evidence that they can rebuild the complex histologic structure of native pulp in situ with highly organized physiologic patterns or even achieve de novo regeneration of complete dental pulp tissues. More importantly, recent clinical studies emphasized in situ neurovascularization outcomes in successful regeneration of vitalized pulp via pulp stem cell transplantation. In this review, we summarize recent breakthroughs in pulp stem cell–mediated pulp regeneration, emphasizing the crucial achievement of neurovascularization. This functional pulp regeneration represents an innovative and promising approach for future regenerative endodontics.

scholarly journals Delivery of affordable and scalable encapsulated allogenic/autologous mesenchymal stem cells in coagulated platelet poor plasma for dental pulp regeneration

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Ioannis Angelopoulos ◽  
Cesar Trigo ◽  
Maria-Ignacia Ortuzar ◽  
Jimena Cuenca ◽  
Claudia Brizuela ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Dental Pulp ◽  
Cost Effective ◽  
Pulp Regeneration ◽  
Platelet Poor Plasma ◽  
Regenerative Endodontics ◽  
Cell Sources ◽  
Autologous Mesenchymal Stem Cells

AbstractThe main goal of regenerative endodontics procedures (REPs) is to revitalize teeth by the regeneration of healthy dental pulp. In this study, we evaluated the potential of combining a natural and accessible biomaterial based on Platelet Poor Plasma (PPP) as a support for dental pulp stem cells (DPSC) and umbilical cord mesenchymal stem cells (UC-MSC). A comparison study between the two cell sources revealed compatibility with the PPP based scaffold with differences noted in the proliferation and angiogenic properties in vitro. Additionally, the release of growth factors including VEGF, HGF and DMP-1, was detected in the media of cultured PPP and was enhanced by the presence of the encapsulated MSCs. Dentin-Discs from human molars were filled with PPP alone or with MSCs and implanted subcutaneously for 4 weeks in mice. Histological analysis of the MSC-PPP implants revealed a newly formed dentin-like structure evidenced by the expression of Dentin sialophosphoprotein (DSPP). Finally, DPSC induced more vessel formation around the dental discs. This study provides evidence of a cost-effective, xenofree scaffold that is compatible with either autologous or allogenic strategy for dental pulp regeneration. This attempt if successfully implemented, could make REPs treatment widely accessible, contributing in improving global health conditions.

Cell-Based Regenerative Endodontics for Treatment of Periapical Lesions: A Randomized, Controlled Phase I/II Clinical Trial

2020 ◽  
Vol 99 (5) ◽  
pp. 523-529 ◽  
Author(s):  
C. Brizuela ◽  
G. Meza ◽  
D. Urrejola ◽  
M.A. Quezada ◽  
G. Concha ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Phase I ◽  
Umbilical Cord ◽  
Root Canal ◽  
Categorical Variables ◽  
Safety And Efficacy ◽  
Randomized Controlled

A randomized controlled phase I/II clinical trial was designed to evaluate the safety and efficacy of encapsulated human umbilical cord mesenchymal stem cells in a plasma-derived biomaterial for regenerative endodontic procedures (REPs) in mature permanent teeth with apical lesions. The trial included 36 patients with mature incisors, canines, or mandibular premolars showing pulp necrosis and apical periodontitis. Patients were randomly and equally allocated between experimental (REP) or conventional root canal treatment (ENDO) groups. On the first visit, cavity access and mechanical preparation of the root canal were performed. Calcium hydroxide medication was used, and the cavity was sealed. Three weeks later, patients were treated following their assigned protocol of ENDO or REP. Clinical follow-up examinations were performed at 6 and 12 mo. Categorical variables were evaluated by Fisher’s exact test. Quantitative variables were compared using the Mann-Whitney test. The evolution over time of the percentage of perfusion units and the dimensions of lesion and cortical compromise were explored. After the 12-mo follow-up, no adverse events were reported, and the patients showed 100% clinical efficacy in both groups. Interestingly, in the REP group, the perfusion unit percentage measured by laser Doppler flowmetry revealed an increase from 60.6% to 78.1% between baseline and 12-mo follow-up. Sensitivity tests revealed an increase of the positive pulp response in the REP group at 12-mo follow-up (from 6% to 56% on the cold test, from 0% to 28% on the hot test, and from 17% to 50% on the electrical test). We present the first clinical safety and efficacy evidence of the endodontic use of allogenic umbilical cord mesenchymal stem cells encapsulated in a plasma-derived biomaterial. The innovative approach, based on biological principles that promote dentin-pulp regeneration, presents a promising alternative for the treatment of periapical pathology (ClinicalTrials.gov NCT03102879).

scholarly journals Downregulation of miR-224-5p Promotes Migration and Proliferation in Human Dental Pulp Stem Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Zhihong Ke ◽  
Zailing Qiu ◽  
Tingting Xiao ◽  
Jianchai Zeng ◽  
Luning Zou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Root Canal ◽  
Dental Pulp ◽  
Dental Pulp Stem Cells ◽  
Differentially Expressed ◽  
Pulp Regeneration ◽  
Regenerative Endodontics ◽  
Differentially Expressed Mirna ◽  
And Migration ◽  
Proliferation And Migration

Introduction. Pulp regeneration, as a treatment for pulp necrosis, has significant advantages over root canal therapy for the preservation of living pulp. To date, research on pulp regeneration has mainly focused on the transplantation of pulp stem cells into the root canal, but there is still a lack of research on the migration of pulp cells into the root canal via cell homing. Stem cells from the apical tooth papilla (SCAP) are recognized as multidirectional stem cells, but these cells are difficult to obtain. MicroRNAs are small noncoding RNAs that play crucial roles in regulating normal and pathologic functions. We hypothesized that some types of microRNAs might improve the migration and proliferation function of dental pulp stem cells (DPSCs), which are easily obtained in clinical practice, and as a result, DPSCs might replace SCAP and provide valuable information for regenerative endodontics. Methods. Magnetic activated cell sorting of DPSCs and SCAP was performed. Next-generation sequencing was performed to examine DPSCs and SCAP miRNAs expression and to identify the most significant differentially expressed miRNA. CCK-8 and transwell assays were used to determine the impact of this miRNA on DPSCs proliferation and migration. Results. The most significant differentially expressed miRNA between DPSCs and SCAP was miR-224-5p. Downregulating miR-224-5p promoted DPSCs proliferation and migration; the opposite results were observed when miR-224-5p was upregulated. Conclusion. MiR-224-5p promotes proliferation and migration in DPSCs, a finding that is of great significance for further exploring the role of dental pulp stem cells in regenerative endodontics.

scholarly journals CD146 controls the quality of clinical grade mesenchymal stem cells from human dental pulp

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lan Ma ◽  
Zhiqing Huang ◽  
Di Wu ◽  
Xiaoxing Kou ◽  
Xueli Mao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Dental Pulp ◽  
Culture Conditions ◽  
Proliferation Rate ◽  
Permanent Teeth ◽  
Deciduous Teeth ◽  
Clinical Grade ◽  
Surface Molecule ◽  
Differentiation Potential

Abstract Background Human mesenchymal stem cells from dental pulp (hMSC-DP), including dental pulp stem cells from permanent teeth and exfoliated deciduous teeth, possess unique MSC characteristics such as expression of specific surface molecules and a high proliferation rate. Since hMSC-DP have been applied in numerous clinical studies, it is necessary to establish criteria to evaluate their potency for cell-based therapies. Methods We compared stem cell properties of hMSC-DP at passages 5, 10 and 20 under serum (SE) and serum-free (SF) culture conditions. Cell morphology, proliferation capacity, chromosomal stability, surface phenotypic profiles, differentiation and immunoregulation ability were evaluated. In addition, we assessed surface molecule that regulates hMSC-DP proliferation and immunomodulation. Results hMSC-DP exhibited a decrease in proliferation rate and differentiation potential, as well as a reduced expression of CD146 when cultured under continuous passage conditions. SF culture conditions failed to alter surface marker expression, chromosome stability or proliferation rate when compared to SE culture. SF-cultured hMSC-DP were able to differentiate into osteogenic, adipogenic and neural cells, and displayed the capacity to regulate immune responses. Notably, the expression level of CD146 showed a positive correlation with proliferation, differentiation, and immunomodulation, suggesting that CD146 can serve as a surface molecule to evaluate the potency of hMSC-DP. Mechanistically, we found that CD146 regulates proliferation and immunomodulation of hMSC-DP through the ERK/p-ERK pathway. Conclusion This study indicates that SF-cultured hMSC-DP are appropriate for producing clinical-grade cells. CD146 is a functional surface molecule to assess the potency of hMSC-DP.

scholarly journals Present Status of Research on the Regenerative Potential of Dental Pulp Stem Cells in Malaysia: A Systematic Review

2021 ◽  
Vol 8 (1) ◽  
pp. 304-309
Author(s):  
Nazmul Haque
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Present Status ◽  
Dental Pulp ◽  
Dental Pulp Stem Cells ◽  
Permanent Teeth ◽  
Deciduous Teeth ◽  
Invasive Technique ◽  
Human Exfoliated Deciduous Teeth

Stem cells from human exfoliated deciduous teeth (SHED) or dental pulp stem cells (DPSCs) from permanent teeth are considered promising sources of mesenchymal stem cells. It requires a less invasive technique to isolate stem cells from exfoliated or permanent teeth. Hence this study aimed to identify the present status of research on the regenerative potential of SHED/DPSCs in Malaysia. The results indicate that only 60 articles were published in regenerative medicine from Malaysia till 5th July 2019. Only 16 tertiary institutes and four industries/clinics were involved in these studies. A poor pattern of collaboration has also been identified. Outcomes of this study have emphasized the conduction of more research on the regenerative potential of SHED/DPSCs, and active collaboration among the tertiary institutes and industries for successful translation of these cells from bench side to bedside.

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