Transplantation of Allogeneic MSC in Patients With Pulp Necrosis and Chronic Apical Periodontitis

NCT04545307 | Completed Phase 2 DMC

• 1 other identifier: MSCYPPNAP001
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to evaluate the effect of Mesenchymal Stromal Cell (MSC) implantation on pulp and periapical regeneration of immature teeth with pulp necrosis and chronic apical periodontitis. BACKGROUND:

• Post-traumatic pulp necrosis prevents root development in children and adolescents.
• The multipotent ability of MSC to differentiate into bone-forming cells (osteoblasts) and dentin-forming cells (Odontoblast) has allowed the development of protocols to induce dental pulp regeneration in preclinical models and patients with immature teeth with pulpal necrosis. IMPACT:
• Worldwide, post-traumatic pulp necrosis in children and adolescents constitutes a health problem in the endodontic area.
• Treatment with MSC would provide an effective therapeutic alternative to patients with pulp necrosis and incomplete root formation.
• The possible pulp and periapical regeneration of immature teeth induced by MSC would have a huge impact on the treatment of these patients. Eligibility for EMC implant study Age: 6 to 16 years Sex: Male or Female Healthy volunteers accepted: NO. TREATMENT GROUPS: In the present study, the implantation of MSC will be performed in patients with immature teeth with pulpal necrosis with apical periodontitis, who will receive the appropriate endodontic treatment (according to the guidelines of the American Association of Endodontics) and implantation of allogeneic BM-MSC . This group will be compared with the history made in the Postgraduate Endodontics of the Universidad Central de Venezuela (UCV) and with international case series made by revascularization. Clinical follow-up of each patient:
• Clinical controls (facial evaluation, gingival evaluation, apical palpation, horizontal and vertical percussion, cold and heat sensitivity tests) will be carried out on days 0, 7, 30, 90, 180 and 364. Additionally, a clinical evaluation will be carried out at the two years post-implantation of MSC.
• Radiological controls will be carried out on days 0, 7, 30, 90, 180 and 364. Additionally, they will be carried out two years post-implantation of MSC.
• A tomographic evaluation will be performed when was evident periapical repair in a periapical radiograph. To measure root formation, root canal narrowing and verification the periapical repair in 3D.

Conditions

Pulp Necroses; Apical Periodontitis

Keywords

BM-MSC; Pulp regeneration

Outcome Measures

Primary Outcomes (5)

• Sings and Symptoms Absence

  Through clinical inspection evaluate absence of fistula, intra or extra oral inflammation, no tender to percussion or a palpation

  15 days post implant

• Root canal Narrowing

  Through periodical radiographs measure the root canal lumen months after months to evaluate any reduction of the lumen

  6 to 12 months

• Elongation of the root

  Through periodical radiographs measure the teeth length from the incisal border to the apex month after month to evaluate any increase of the root length

  6 to 12 month

• Sensitivity tests perception

  With the aid of pulpometer and Endo Ice evaluate if the patient start to feel any stimulation

  6 to 12 months

• Repair of the bone lesion produced by the apical periodontitis

  Through a periodical radiograph evaluate month after month the increase of radiopacity in the radiolucent area produced by the apical periodontitis. When an evident repair is confirmed a tomography study will be carry out to evaluate it in 3D

  12 to 24 months

Secondary Outcomes (2)

• Stability of bio ceramic cements used in the obturation of the access cavity

  6 to 12 months

• Evaluate blood circulation within the root canal

  6 to 24 months

Study Arms (1)

Allogenic transplant of BM-MSCs

EXPERIMENTAL

Under sterile conditions, the patient will be locally anesthetized in the affected tooth area; the root canal of the affected tooth will be exposed and prepared to perform the MSC / MSC-Endo / PRP implant. At the same time, the culture medium supernatant is removed from each tube and the MSC / MSC-Endo "button (pellet)" is resuspended in autologous platelet-rich plasma (PRP). Subsequently to the MSC / MSC-Endo / PRP suspension, 5% CaCl2 and thrombin will be added. Immediately, and before the clot forms, 20 microliters of the MSC / MSC-Endo / PRP suspension will be placed in the root canal, covered with a collagen membrane. Subsequently, the obturation procedure with bioceramics will be carried out at the level of the pulp chamber, ionomeric glass to protect the bioceramic and later composite resin to restore the tooth.

Biological: Allogenic transplant of BM-MSC in a root canal from patients with immature apexes and pulpar necrosis and apical periodontitis

Interventions

Allogenic transplant of BM-MSC in a root canal from patients with immature apexes and pulpar necrosis and apical periodontitis BIOLOGICAL

The implant of BM-MSC/MSC-Endo/PRP in a clean and shaped root canal from patients with immature apexes and pulpal necroses and apical periodontitis

Allogenic transplant of BM-MSCs

Eligibility Criteria

• Age: 6 Years - 16 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Diagnosis of pulp necrosis and apical periodontitis in teeth with immature apices.
• Informed consent by the patient's representative and consent by the patient to receive bone marrow allogeneic mesenchymal stromal cell transplantation treatment.

You may not qualify if:

• HIV positive
• Hepatitits B or C positive
• Autoimmune diseases: lupus, rheumatoid arthritis.
• Neoplastic diseases.
• Major metabolic disorders
• Pregnancy
• Being on steroid treatment

Sponsors & Collaborators

• Universidad Central de Venezuela: lead
• Instituto Venezolano de Investigaciones Cientificas: collaborator

Study Sites (1)

Unidad de Terapia Celular del Instituto de Investigaciones Científicas

San Antonio de Los Altos, Miranda, 1020-A, Venezuela

Location

Related Publications (18)

• Antunes LS, Salles AG, Gomes CC, Andrade TB, Delmindo MP, Antunes LA. The effectiveness of pulp revascularization in root formation of necrotic immature permanent teeth: A systematic review. Acta Odontol Scand. 2016;74(3):161-9. doi: 10.3109/00016357.2015.1069394. Epub 2015 Jul 15.

  PMID: 26179397 BACKGROUND

• Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem. 2006 Aug 1;98(5):1076-84. doi: 10.1002/jcb.20886.

  PMID: 16619257 BACKGROUND

• Diaz-Solano D, Wittig O, Mota JD, Cardier JE. Isolation and Characterization of Multipotential Mesenchymal Stromal Cells from Congenital Pseudoarthrosis of the Tibia: Case Report. Anat Rec (Hoboken). 2015 Oct;298(10):1804-14. doi: 10.1002/ar.23198. Epub 2015 Jul 30.

  PMID: 26194170 BACKGROUND

• Eramo S, Natali A, Pinna R, Milia E. Dental pulp regeneration via cell homing. Int Endod J. 2018 Apr;51(4):405-419. doi: 10.1111/iej.12868. Epub 2017 Nov 7.

  PMID: 29047120 BACKGROUND

• Fouad AF. Microbiological aspects of traumatic injuries. Dent Traumatol. 2019 Dec;35(6):324-332. doi: 10.1111/edt.12494. Epub 2019 Oct 14.

  PMID: 31125490 BACKGROUND

• Guerrero F, Mendoza A, Ribas D, Aspiazu K. Apexification: A systematic review. J Conserv Dent. 2018 Sep-Oct;21(5):462-465. doi: 10.4103/JCD.JCD_96_18.

  PMID: 30294103 BACKGROUND

• Hawryluk GW, Mothe A, Wang J, Wang S, Tator C, Fehlings MG. An in vivo characterization of trophic factor production following neural precursor cell or bone marrow stromal cell transplantation for spinal cord injury. Stem Cells Dev. 2012 Aug 10;21(12):2222-38. doi: 10.1089/scd.2011.0596. Epub 2012 Feb 7.

  PMID: 22085254 BACKGROUND

• Huang GT. Dental pulp and dentin tissue engineering and regeneration: advancement and challenge. Front Biosci (Elite Ed). 2011 Jan 1;3(2):788-800. doi: 10.2741/e286.

  PMID: 21196351 BACKGROUND

• Iohara K, Nakashima M, Ito M, Ishikawa M, Nakasima A, Akamine A. Dentin regeneration by dental pulp stem cell therapy with recombinant human bone morphogenetic protein 2. J Dent Res. 2004 Aug;83(8):590-5. doi: 10.1177/154405910408300802.

  PMID: 15271965 BACKGROUND

• Moradi S, Talati A, Forghani M, Jafarian AH, Naseri M, Shojaeian S. Immunohistological Evaluation of Revascularized Immature Permanent Necrotic Teeth Treated by Platelet-Rich Plasma: An Animal Investigation. Cell J. 2016 Fall;18(3):389-96. doi: 10.22074/cellj.2016.4567. Epub 2016 Aug 24.

  PMID: 27602321 BACKGROUND

• Murakami M, Hayashi Y, Iohara K, Osako Y, Hirose Y, Nakashima M. Trophic Effects and Regenerative Potential of Mobilized Mesenchymal Stem Cells From Bone Marrow and Adipose Tissue as Alternative Cell Sources for Pulp/Dentin Regeneration. Cell Transplant. 2015;24(9):1753-65. doi: 10.3727/096368914X683502. Epub 2014 Jul 30.

  PMID: 25199044 BACKGROUND

• Nakashima M, Iohara K. Regeneration of dental pulp by stem cells. Adv Dent Res. 2011 Jul;23(3):313-9. doi: 10.1177/0022034511405323.

  PMID: 21677085 BACKGROUND

• Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science. 1999 Apr 2;284(5411):143-7. doi: 10.1126/science.284.5411.143.

  PMID: 10102814 BACKGROUND

• Shammaa R, El-Kadiry AE, Abusarah J, Rafei M. Mesenchymal Stem Cells Beyond Regenerative Medicine. Front Cell Dev Biol. 2020 Feb 18;8:72. doi: 10.3389/fcell.2020.00072. eCollection 2020.

  PMID: 32133358 BACKGROUND

• Wang X, Thibodeau B, Trope M, Lin LM, Huang GT. Histologic characterization of regenerated tissues in canal space after the revitalization/revascularization procedure of immature dog teeth with apical periodontitis. J Endod. 2010 Jan;36(1):56-63. doi: 10.1016/j.joen.2009.09.039.

  PMID: 20003936 BACKGROUND

• Wittig O, Diaz-Solano D, Cardier J. Viability and functionality of mesenchymal stromal cells loaded on collagen microspheres and incorporated into plasma clots for orthopaedic application: Effect of storage conditions. Injury. 2018 Jun;49(6):1052-1057. doi: 10.1016/j.injury.2018.04.005. Epub 2018 Apr 5.

  PMID: 29678307 BACKGROUND

• Wittig O, Romano E, Gonzalez C, Diaz-Solano D, Marquez ME, Tovar P, Aoun R, Cardier JE. A method of treatment for nonunion after fractures using mesenchymal stromal cells loaded on collagen microspheres and incorporated into platelet-rich plasma clots. Int Orthop. 2016 May;40(5):1033-8. doi: 10.1007/s00264-016-3130-6. Epub 2016 Mar 16.

  PMID: 26980620 BACKGROUND

• Xuan K, Li B, Guo H, Sun W, Kou X, He X, Zhang Y, Sun J, Liu A, Liao L, Liu S, Liu W, Hu C, Shi S, Jin Y. Deciduous autologous tooth stem cells regenerate dental pulp after implantation into injured teeth. Sci Transl Med. 2018 Aug 22;10(455):eaaf3227. doi: 10.1126/scitranslmed.aaf3227.

  PMID: 30135248 BACKGROUND

MeSH Terms

Conditions

Dental Pulp Necrosis; Periapical Periodontitis

Condition Hierarchy (Ancestors)

Dental Pulp Diseases; Tooth Diseases; Stomatognathic Diseases; Necrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Periapical Diseases; Jaw Diseases; Periodontal Diseases; Mouth Diseases; Periodontitis

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: DDS, PhD

Model Details: PRP clot loaded of BM-MSC in order to regenerate dental pulp tissue, placed in the root canal of an immature tooth from a patient with pulp necrosis and chronic apical periodontitis

Study Record Dates

• First Submitted: September 3, 2020
• First Posted: September 11, 2020
• Study Start: November 27, 2019
• Primary Completion: December 27, 2019
• Study Completion: January 27, 2020
• Last Updated: September 16, 2020

Record last verified: 2020-09

Locations

VE (1)