Cell-Based Transplantation versus Cell Homing Approaches for Pulp-Dentin Complex Regeneration
Table 2
Summary of cell homing studies for pulp-dentin complex regeneration.
Study
Study design
Outcomes
Blind; random; design
Animal model/human
Type of study
Groups
Primary outcomes
Secondary outcomes
Histology
Clinically and radiographically
Discoloration and sensibility test
Thibodeau et al. 2007
Randomized clinical study
Animal study; 60 immature teeth from 6 dogs
Cell homing
Group 1: no treatment (but disinfected) Group 2: blood clot Group 3: collagen solution Group 4: collagen solution+blood clot Group 5: negative control (left untouched)
Radiographic thickening of root canal walls, apical closure, and healing of periapical radiolucency in all the groups
Hard tissue deposition on radicular dentin in all groups except the negative control New vital tissues were formed in the root canals in all groups except in the negative group.
Shah et al. 2008
Pilot clinical study
14 cases of infected immature teeth
Cell homing
Blood clot revascularization
Radiographic resolution of periapical radiolucencies was judged to be good to excellent in 93% of the cases. The striking finding was complete resolution of clinical signs and symptoms and appreciable healing of periapical lesions in 78% of cases.
Ding et al. 2009
Clinical study
12 patients, each with immature permanent tooth with chronic or acute apical periodontitis
Cell homing
Blood clot revascularization
Teeth () were found to exhibit complete root development with a positive response to pulp testing.
Lovelace et al. 2011
Clinical study
A total of 12 patients were included in this study.
Cell homing
This study consisted of 6 boys and 6 girls with immature permanent maxillary or mandibular single rooted immature tooth with open apices with diagnosis of pulp necrosis with apical periodontitis.
Molecular analyses of blood collected from the canal system indicated the significant accumulation of transcripts for stem cell markers CD73 and CD105 (up to 600-fold).
Histological analysis demonstrated that the delivered cells expressed both CD105 and STRO-1, markers for a subpopulation of mesenchymal stem cells.
Jadhav et al. 2012
Pilot clinical study
20 patients with nonvital, immature anterior teeth were randomly categorized into 2 groups; revascularization with or without PRP
Cell homing
Group I: blood clot Group II: using PRP
Clinically, all cases were asymptomatic with complete resolution of signs and symptoms. Radiographically, there was a marked difference in periapical healing, apical closure, and dentinal wall thickening in group II in comparison with group I; however, root lengthening was comparable for both of the procedures.
Shimizu et al. 2012
Case report
Human study
Cell homing
Revascularization/regeneration procedure
At 3.5 weeks after revascularization, more than one half of the canal was filled with loose connective tissue similar to the pulp tissue. A layer of flattened odontoblast-like cells lined along the predentin. Layers of epithelial-like cells, similar to the Hertwig’s epithelial root sheath, surrounded the root apex. No hard tissue was formed in the canal.
Mishra et al. 2013
Case report
An 11-year-old boy with the history of trauma was diagnosed with pulpal necrosis and symptomatic apical periodontitis in tooth #21.
Cell homing
Platelet-rich fibrin used
Clinical examination at 6 and 12 months revealed no sensitivity to percussion and palpation in tooth #21, and it responded positively to both electric pulp and cold tests. Radiographic examination showed resolution of periapical rarefaction, further root development and apical closure of the tooth #21 and its associated supernumerary tooth.
Zhang et al. 2014
Randomized clinical study
Animal study; three 6-month-old beagles
Cell homing
Group 1: PRP Group 2: blood clot Group 3: negative control
Apical apex was closed. Pulp-like tissue (fibroblasts and blood vessels) was developed. Thickening of the canal wall with ingrowth of cellular cementum-like tissues (cementocyte-like cells) were present in the newly formed tissues. Large number of inflammatory cells were present in the PRP and blood clot groups.
Priya et al. 2015
Clinical case study
The present case evaluated PRP for pulpal regeneration in an avulsed mature incisor (>8-hour extraoral dry time) of an 11-year-old boy after delayed replantation.
Cell homing
The present case evaluated PRP for pulpal regeneration in an avulsed mature incisor (>8-hour extraoral dry time) of an 11-year-old boy after delayed replantation.
Nine- and 12-month radiographs revealed resolution of periapical radiolucency with no further progression of internal resorption. The tooth showed a positive response to thermal and electric pulp tests. The findings observed in this case warrant further research under controlled conditions to evaluate endodontic and periodontal regeneration in a tooth that would otherwise be expected to have an unfavourable prognosis.
El Ashiry et al. 2016
Clinical study
20 patients with immature necrotic teeth with apical periodontitis
Cell homing
Blood clot group
Within 12-24 months, increase in dentinal wall thickness and root length and continued root development were observed.
Shivashankar et al. 2017
Triple-blind randomized clinical trial
60 patients with necrotic immature tooth
Cell homing
Group A: PRF (scaffold) Group B: revascularization with conventional induced bleeding Group C: PRP (biomaterial)
At the end of 12 months, patients presented no pain and no signs of reinfection. No radiographic enlargement of the preexisting apical pathosis in all the three groups
Song et al. 2017
Retrospective study
29 cases undergone revascularization between 2010 and 2014.
Cell homing
Revascularization group
Continued root development with apical closure in 79.35 of cases Revascularization associated intracanal calcification in 62.1% of the cases after 12-month follow-up
Nageh et al. 2018
Clinical study
15 patients with necrotic pulp with symptomatic or asymptomatic apical periodontitis
Cell homing
PRF revascularization
All teeth survived after 12 months, no pain or swelling.
Pulp sensibility regained using electric pulp tester in 9 cases after 12-month follow-up.
Neelamurthy et al. 2018
Clinical study
15 patients with immature and mature permanent teeth with pulpal necrosis and open apices
Cell homing
Bleeding group
After 10 months, 10 out of 13 patients showed root development and apical closure.
2 out of 13 patients showed a positive response to electric sensibility test.
Arslan et al. 2019
Randomized clinical study
56 mature necrotic teeth with large periapical radiolucency
Cell homing
Group I: conventional root canal treatment (CRCT) Group II: regenerative endodontic procedures (REP)
No difference between the two groups regarding pain, palpation, swelling, sinus tract, and pain on percussion. Radiologically, absence and reduction of the radiolucency were 85% in the CRCT group and 92.4% in the REP group.
50% of REP-treated teeth responded positively to electrical vitality testing.
Mittal et al. 2019
Clinical study
16 cases of necrotic immature permanent teeth using PRF, collagen, Placentrex, and chitosan
Cell homing
Group I: PRF Group II: collagen Group III: Placentrex Group IV: chitosan
Clinically, patients were completely asymptomatic throughout the study period. Radiographically, all cases showed an improvement in terms of periapical healing, apical closure, root lengthening, and dentinal wall thickening. PRF and collagen gave better results than Placentrex and chitosan in terms of periapical healing, apical closure, and dentinal wall thickening.
Ragab et al. 2019
Randomized controlled trial
22 patients suffering from immature necrotic permanent maxillary central incisors
Cell homing
Group A: blood clot Group B: using PRF revascularization
After a follow-up period of 12 months, most of the cases showed radiographic evidence of periapical healing and showed calcific bridges either cervical and/or apical.
Arora et al. 2020
Case series
9 patients with infected immature molars
Cell homing
Bleeding group
After 60 months, all teeth showed continued root development and maintained functionality.
None responded to vitality testing.
Elsheshtawy et al. 2020
Randomized controlled trial
26 patients with immature permanent anterior teeth with necrotic pulps
Cell homing
Group 1: PRP (test) Group 2: blood clot (control)
All cases in both groups showed complete healing after 3 months. One tooth in the PRP group had signs of reinfection after 6 months. In both groups, there was increase in root lengths and dentinal root widths and decrease in the apical foramen width and periapical area diameter.
No change in pulp sensibility using thermal and electrical pulp testing
Rizk et al. 2020
Double-blinded randomized controlled trial
26 patients with maxillary permanent immature central incisors
Cell homing
Group I: PRP (scaffold) Group II: PRF (scaffold)
All teeth were survived after 12 months. Both groups showed marginal increase in radiographic root length and width. Increase in periapical bone density Decrease in apical diameter
