Abstract
Introduction
The transplantation of dental pulp stem cells (DPSCs) has emerged as a novel strategy
for the regeneration of lost dental pulp after pulpitis and trauma. Dental pulp regeneration
of the young permanent tooth with a wide tooth apical foramen has achieved significant
progress in the clinical trials. However, because of the narrow apical foramen, dental
pulp regeneration in adult teeth using stem cells remains difficult in the clinic.
Finding out how to promote vascular reconstitution is essential for the survival of
stem cells and the regeneration of dental pulp after transplantation into the adult
tooth.
Methods
Adipose tissue–derived microvascular fragments (ad-MVFs) were isolated from human
adipose tissues. The apoptosis and senescence of DPSCs cultured in conditioned media
were evaluated to explore the effects of ad-MVFs on DPSCs. DPSCs combined with ad-MVFs
were inserted into the human tooth root segments and implanted subcutaneously into
immunodeficient mice. Regenerated pulplike tissues were analyzed by hematoxylin and
eosin and immunohistochemistry. The vessels in regenerated tissues were analyzed by
Micro-CT and immunofluorescence.
Results
The isolated ad-MVFs contained endothelial cells and pericytes. ad-MVFs effectively
prevented the apoptosis and senescence of the transplanted DPSCs both in vivo and in vitro. Combined with DPSCs, ad-MVFs obviously facilitated the formation of vascular networks
in the transplants. DPSCs combined with ad-MVFs formed dental pulp–like tissues with
abundant cells and matrix after 4 weeks of implantation. The supplementation of ad-MVFs
led to more odontoblastlike cells and increased the formation of mineralized substance
around the root canal.
Conclusions
Cotransplantation with ad-MVFs promotes the angiogenesis and revascularization of
transplanted DPSC aggregates, leading to robust regeneration of dental pulp.
Key Words
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References
- How biomechanics can affect the endodontic treated teeth and their restorative procedures?.Braz Oral Res. 2018; 32: e76
- Innovative dental stem cell-based research approaches: the future of dentistry.Stem Cells Int. 2016; 2016: 7231038
- Deciduous autologous tooth stem cells regenerate dental pulp after implantation into injured teeth.Sci Transl Med. 2018; 10: eaaf3227
- Pulp regeneration: current approaches and future challenges.Front Physiol. 2016; 7: 58
- Pulp vascularization during tooth development, regeneration, and therapy.J Dent Res. 2017; 96: 137-144
- Vascularization in tissue engineering.Trends Biotechnol. 2008; 26: 434-441
- Large-scale time series microscopy of neovessel growth during angiogenesis.Angiogenesis. 2015; 18: 219-232
- The interplay of dental pulp stem cells and endothelial cells in an injectable peptide hydrogel on angiogenesis and pulp regeneration in vivo.Tissue Eng Part A. 2015; 21: 550-563
- GelMA-encapsulated hDPSCs and HUVECs for dental pulp regeneration.J Dent Res. 2017; 96: 192-199
- Adipose tissue-derived microvascular fragments improve vascularization, lymphangiogenesis, and integration of dermal skin substitutes.J Invest Dermatol. 2017; 137: 217-227
- Microvascular transplantation after acute myocardial infarction.Tissue Eng. 2007; 13: 2871-2879
- An islet-stabilizing implant constructed using a preformed vasculature.Tissue Eng Part A. 2008; 14: 433-440
- Prevascularization of dermal substitutes with adipose tissue-derived microvascular fragments enhances early skin grafting.Sci Rep. 2018; 8: 10977
- Vascularisation of porous scaffolds is improved by incorporation of adipose tissue-derived microvascular fragments.Eur Cell Mater. 2012; 24: 266-277
- Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo.Proc Natl Acad Sci U S A. 2000; 97: 13625-13630
- Human treated dentin matrix as a natural scaffold for complete human dentin tissue regeneration.Biomaterials. 2011; 32: 4525-4538
- Isolation of murine adipose tissue-derived microvascular fragments as vascularization units for tissue engineering.J Vis Exp. 2017; 122: 55721
- NIH Image to ImageJ: 25 years of image analysis.Nat Methods. 2012; 9: 671-675
- Pulp regeneration in a full-length human tooth root using a hierarchical nanofibrous microsphere system.Acta Biomater. 2016; 35: 57-67
- Seeding density is a crucial determinant for the in vivo vascularisation capacity of adipose tissue-derived microvascular fragments.Eur Cell Mater. 2017; 34: 55-69
- Development of in vivo muCT evaluation of neovascularisation in tissue engineered bone constructs.Bone. 2008; 43: 195-202
- Stem/progenitor cell-mediated de novo regeneration of dental pulp with newly deposited continuous layer of dentin in an in vivo model.Tissue Eng Part A. 2010; 16: 605-615
- Decellularized swine dental pulp tissue for regenerative root canal therapy.J Dent Res. 2018; 97: 1460-1467
- Scaffold-free prevascularized microtissue spheroids for pulp regeneration.J Dent Res. 2014; 93: 1296-1303
- Characterization and multilineage potential of cells derived from isolated microvascular fragments.J Surg Res. 2014; 192: 214-222
- Angiogenic potential of microvessel fragments established in three- dimensional collagen gels.Vitro Cell Dev Biol Anim. 1996; 32: 409-419
- The PI3k/Akt pathway is associated with angiogenesis, oxidative stress and survival of mesenchymal stem cells in pathophysiologic condition in ischemia.Physiol Res. 2019; 68: S131-S138
- Oxidative stress in mesenchymal stem cell senescence: regulation by coding and noncoding RNAs.Antioxid Redox Signal. 2018; 29: 864-879
- Insight on stem cell preconditioning and instructive biomaterials to enhance cell adhesion, retention, and engraftment for tissue repair.Biomaterials. 2016; 90: 85-115
- Implanted microvessels progress through distinct neovascularization phenotypes.Microvasc Res. 2010; 79: 10-20
- Dentin sialoprotein and dentin phosphoprotein have distinct roles in dentin mineralization.Matrix Biol. 2009; 28: 221-229
- Human umbilical cord mesenchymal stem cells: a new therapeutic option for tooth regeneration.Stem Cells Int. 2015; 2015: 549432
- Adipose tissue-derived microvascular fragments: natural vascularization units for regenerative medicine.Trends Biotechnol. 2015; 33: 442-448
- A comparison of laterally condensed gutta-percha, thermoplasticized gutta-percha, and mineral trioxide aggregate as root canal filling materials.J Endod. 2004; 30: 103-106
- Mineral trioxide aggregate: a comprehensive literature review--part III: clinical applications, drawbacks, and mechanism of action.J Endod. 2010; 36: 400-413
Article info
Publication history
Published online: April 19, 2021
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© 2021 American Association of Endodontists.