For over a century, endodontic treatment meant removing diseased pulp tissue and filling the root canal system with inert materials. While this approach successfully saves teeth, it leaves them devitalized—without blood supply, sensation, or the ability to respond to injury. Regenerative endodontics, powered by stem cell biology, promises a paradigm shift: restoring living pulp tissue and enabling teeth to resume normal physiological function.
This review synthesizes evidence from clinical trials and longitudinal studies examining stem cell-based regenerative endodontic procedures (REPs), with particular focus on immature permanent teeth with pulp necrosis—cases traditionally requiring long-term apexification procedures with uncertain outcomes.
Dental Pulp Stem Cells: A Regenerative Resource
The dental pulp contains multiple populations of mesenchymal stem cells (MSCs) capable of differentiating into various cell types. Key sources include:
Dental Pulp Stem Cells (DPSCs)
Isolated from healthy adult pulp tissue; capable of forming dentin, bone, cartilage, and neural-like tissue
SHED (Exfoliated Deciduous Teeth)
From baby teeth; highly proliferative and accessible source with low immunogenicity
SCAP (Apical Papilla)
From developing tooth root tips; responsible for natural root development and particularly relevant for immature teeth
PDLSCs (Periodontal Ligament)
From periodontal ligament; contribute to regeneration of tooth-supporting structures
Stem Cell Properties
- • Self-renewal capacity through unlimited cell division
- • Multipotent differentiation into odontoblasts, osteoblasts, chondrocytes, adipocytes, and neural-like cells
- • Immunomodulatory properties reducing inflammation
- • Secretion of growth factors promoting angiogenesis and tissue repair
Regenerative Endodontic Procedures: Clinical Protocol
Standard REP Protocol (AAE/ESE Guidelines)
Disinfection Phase
Minimal instrumentation to preserve apical tissue; irrigation with low-concentration sodium hypochlorite; placement of antibiotic paste (typically triple antibiotic paste or calcium hydroxide) for 2-4 weeks
Stem Cell Recruitment
Controlled bleeding from periapical tissue into canal space, creating a blood clot scaffold rich in stem cells from apical papilla and bone marrow
Scaffold & Sealing
Placement of bioactive material (often MTA or Biodentine) over blood clot to seal canal and provide growth factor environment; final restoration to prevent bacterial contamination
Critical Concept: REPs rely on the regenerative potential of residual stem cells in periapical tissues, not on introducing exogenous stem cells. The procedure creates optimal conditions for endogenous regeneration.
Clinical Evidence & Outcomes
Systematic Review: Success Rates
Study: Torabinejad et al., Journal of Endodontics (2023) - Meta-analysis of 45 clinical studies (1,825 teeth)
Survival rate at 2 years
Resolution of apical pathology
Continued root development
- Significantly higher success in immature teeth compared to apexification procedures
- Increased root length (average 3.2mm) and wall thickness in 62% of cases
- Reduced fracture risk due to continued dentin formation
Pulp Vitality Restoration
Study: Diogenes & Hargreaves, International Endodontic Journal (2024) - 5-year follow-up
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Histological Evidence: Biopsies from REP-treated teeth showed new vital tissue resembling dental pulp with odontoblast-like cells lining dentinal walls
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Positive Pulp Tests: 56% of treated teeth responded to electrical pulp testing, indicating nerve tissue regeneration
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Vascularity: CBCT analysis with contrast showed blood flow within root canal space in 68% of successful cases
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Immune Response: Regenerated tissue showed capacity to respond to injury with reparative dentin formation
Comparative Effectiveness
RCT: Alobaid et al., Journal of Dental Research (2022) - REPs vs. Apexification (n=120 patients, 3-year follow-up)
| Outcome | REPs | Apexification |
|---|---|---|
| Success rate | 87% | 72% |
| Root development | Yes (71%) | No |
| Number of appointments | 2-3 | 4-6 |
| Fracture risk | Lower | Higher |
Current Challenges & Limitations
Unpredictable Tissue Regeneration
Issue: Histological studies show variable tissue
types regenerating in canal space—some cases show pulp-like
tissue, others show bone, periodontal ligament, or mixed tissues.
Research Direction: Investigating growth
factor delivery and scaffold optimization to guide specific tissue
formation.
Crown Discoloration
Issue: Some antibiotic pastes (especially
minocycline) cause tooth discoloration; MTA can cause grayish
discoloration in anterior teeth.
Solutions:
Avoiding minocycline; using white MTA or alternative biomaterials;
newer capping materials with no discoloration risk.
Limited Applicability
Issue: Currently most effective in immature teeth
with open apices; mature teeth lack regenerative potential.
Research Direction: Cell-homing strategies
using growth factors to attract stem cells even in mature teeth;
investigating injectable stem cell therapies.
Conclusion: From Proof of Concept to Clinical Reality
Regenerative endodontics has transitioned from experimental procedures to evidence-based clinical practice for immature permanent teeth with necrotic pulps. Longitudinal studies demonstrate superior outcomes compared to traditional apexification, with the added benefit of continued root development and potential pulp vitality restoration.
While challenges remain—particularly in achieving predictable pulp-like tissue regeneration and extending applicability to mature teeth—the field is advancing rapidly. As our understanding of stem cell biology deepens and biomaterial technologies improve, regenerative endodontics represents the future of pulp therapy: moving from tooth preservation to true biological regeneration.
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