Dental Pulpal Tissue Regeneration, Pulpal Vitality Testing, and Healing of Apical Lesions Following Stem Cell Transplant: A Systematic Review and Meta-Analysis

Jamali, Samira; Mousavi, Elnaz; Darvish, Maryam; Jabbari, Golchin; Nasrabadi, Navid; Ahmadizadeh, Hashem

doi:10.1590/pboci.2020.043

Samira Jamali Author to whom correspondence should be addressed: Samira Jamal, Department of Endodontics, Stomatological Hospital, College of Medicine, Xi'an Jiaotong University, Shaanxi 710004, PR China. Phone: +86 29 82655450. E-mail: samira.jamali90@yahoo.com.

Department of Endodontics, Stomatological Hospital, College of Medicine, Xi'an Jiaotong University, Shaanxi, China.

http://orcid.org/0000-0003-3803-1235

Elnaz Mousavi

Dental Sciences Research Center, Department of Endodontics, School of Dentistry, Guilan University of Medical Sciences, Rasht, Iran.

http://orcid.org/0000-0001-9442-5509

Maryam Darvish

Department of Endodontics, School of Dentistry, Kerman University of Medical Sciences, Kerman, Iran.

http://orcid.org/0000-0002-0622-4895

Golchin Jabbari

Department of Endodontics, Dental School, Urmia University of Medical Sciences, Urmia, Iran.

http://orcid.org/0000-0002-5527-9817

Navid Nasrabadi

Department of Endodontics, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

http://orcid.org/0000-0002-6365-6619

Hashem Ahmadizadeh

School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran.

http://orcid.org/0000-0001-7845-2638

Author to whom correspondence should be addressed: Samira Jamal, Department of Endodontics, Stomatological Hospital, College of Medicine, Xi'an Jiaotong University, Shaanxi 710004, PR China. Phone: +86 29 82655450. E-mail: samira.jamali90@yahoo.com.

Academic Editors: Alessandro Leite Cavalcanti and Wilton Wilney Nascimento Padilha

Authors’ Contributions

SJ Conceptualization, Methodology, Investigation, Formal Analysis, Writing - Original Draft Preparation and Writing - Review and Editing.

EM Writing - Original Draft Preparation and Writing - Review and Editing.

MD Writing - Original Draft Preparation and Writing - Review and Editing.

SJ Conceptualization, Methodology, Investigation, Formal Analysis, Writing - Original Draft Preparation and Writing - Review and Editing.

NN Formal Analysis and Writing - Original Draft Preparation.

HA Writing - Review and Editing.

All authors declare that they contributed to critical review of intellectual content and approval of the final version to be published.

Conflict of Interest

The authors declare no conflicts of interest.

Study/Year	No. Teeth	Animal or Human Model	Blind Random	Design	Stem Cells' Source	Defects	Scaffold/ Carrier	Group
Study/Year	No. Teeth	Animal or Human Model	Blind Random	Design	Stem Cells' Source	Defects	Scaffold/ Carrier	Test	Control
El Ashiry et al. (2018) ^[¹²[12] El Ashiry EA, Alamoudi NM, El Ashiry MK, Bastawy HA, El Derwi DA, Atta HM. Tissue engineering of necrotic dental pulp of immature teeth with apical periodontitis in dogs: radiographic and histological evaluation. J Clin Pediatr Dent 2018;42(5):373-382. https://doi.org/10.17796/1053-4625-42.5.9 https://doi.org/10.17796/1053-4625-42.5.... ^]	36	12 Dogs	Randomly	Split	DPSCs; Autologous	Pulps from crown and root	Chitosan Hydrogel Scaffold	DPSCs + growth factors + scaffold	Growth factors + scaffold
Xuan et al. (2018) ^[⁴[4] Xuan K, Li B, Guo H, Sun W, Kou X, He X, et al. Deciduous autologous tooth stem cells regenerate dental pulp after implantation into injured teeth. Sci Transl Med 2018; 10(455):eaaf3227. https://doi.org/10.1126/scitranslmed.aaf3227. https://doi.org/10.1126/scitranslmed.aaf... ^]	26	40 Patients	Randomly	Parallel	Human Deciduous	------	------	hDPSCc	Apexification (CaOH)
Jia et al. (2016) ^[¹³[13] Jia W, Zhao Y, Yang J, Wang W, Wang X, Ling L, et al. Simvastatin promotes dental pulp stem cell-induced coronal pulp regeneration in pulpotomized teeth. J Endod 2016; 42(7):1049-54. https://doi.org/10.1016/j.joen.2016.03.007. https://doi.org/10.1016/j.joen.2016.03.0... ^]	18	2 Dogs	Randomly	Parallel	Canine DPSCs; Autologous	Pulp chamber until root	Absorbable Gelatin Sponge	1. Canine DPSCs (cDPSCs) 2. SCG group SIM + cDPSCs + gelatin sponge	1. The mineral trioxide aggregate 2. Absorbable gelatin sponge
Iohara et al. (2014) ^[¹⁴[14] Iohara K, Murakami M, Nakata K, Nakashima M. Age-dependent decline in dental pulp regeneration after pulpectomy in dogs. Exp Gerontol 2014; 52:39-45. https://doi.org/10.1016/j.exger.2014.01.020. https://doi.org/10.1016/j.exger.2014.01.... ^]	16	4 Dogs	Randomly	Parallel	MDPSCs; Autologous	Whole pulp removed, apical foramen enlarged to 0.5 mm	Atelocoll Agen Scaffold	young MDPSCs with G-CSF	Aged MDPSCs with G-CSF
Iohara et al. (2013) ^[¹⁰[10] Iohara K, Murakami M, Takeuchi N, Osako Y, Ito M, Ishizaka R, et al. A novel combinatorial therapy with pulp stem cells and granulocyte colony-stimulating factor for total pulp regeneration. Stem Cells Transl Med 2013; 2(7):521-33. https://doi.org/10.5966/sctm.2012-0132. https://doi.org/10.5966/sctm.2012-0132... ^]	72	18 Dogs	Randomly	Parallel	DPSCs; Allogenic	Whole pulp removed, apical foramen enlarged to 0.6 mm	Atelo Collagen; Collagen	1. DPSCs/G-CSF /atelo-collagen 2. DPSCs 3. G-CSF	1. Total pulp cells/ G-CSF 2. Total pulp cells 3. Collagen
Zheng et al. (2012) ^[¹¹[11] Zheng Y, Wang XY, Wang YM, Liu XY, Zhang CM, Hou B, et al. Dentin regeneration using deciduous pulp stem/progenitor cells. J Dent Res 2012; 91(7):676-82. https://doi.org/10.1177/0022034512449834. https://doi.org/10.1177/0022034512449834... ^]	56	7 Mini Pigs	Randomly	Parallel	SHEDs; Allogenic	Pulp chamber defects (3-4 mm diameter)	β-TCP Scaffolds	1. DPSCs/β-TCP	1. Ca(OH)2 2. β-TCP

Study	Pulp Tissue Regeneration (Mean ± SD)		Apical Healing N (%)		Pulp Vitality
	Test	Control	Test	Control	Test	Control
El Ashiry et al. ^[¹²[12] El Ashiry EA, Alamoudi NM, El Ashiry MK, Bastawy HA, El Derwi DA, Atta HM. Tissue engineering of necrotic dental pulp of immature teeth with apical periodontitis in dogs: radiographic and histological evaluation. J Clin Pediatr Dent 2018;42(5):373-382. https://doi.org/10.17796/1053-4625-42.5.9 https://doi.org/10.17796/1053-4625-42.5.... ^]	Not reported	Not reported	12 (83.33%)	(83.33%)	Radicular Walls - N (%)
					12 (91.67%)	12 (25.0%)
					Root Lengthening - N (%)
					12 (75.0%)	12 (16.67%)
					Apical Closure - N (%)
					12 (75.0%)	12 (16.67%)
Xuan et al. ^[⁴[4] Xuan K, Li B, Guo H, Sun W, Kou X, He X, et al. Deciduous autologous tooth stem cells regenerate dental pulp after implantation into injured teeth. Sci Transl Med 2018; 10(455):eaaf3227. https://doi.org/10.1126/scitranslmed.aaf3227. https://doi.org/10.1126/scitranslmed.aaf... ^]	Not reported	Not reported	Not reported	Not reported	Root Lengthening (Mean ± SD)
					10.69 ± 1.32 mm	9.99 ± 0.82 mm
					Apical Closure (Mean ± SD)
					3.17 ± 0.69 mm	3.54 ± 0.44 mm
					Laser Doppler (Mean ± SD)
					2.81 ± 0.41	3.01±0.44
Jia et al. ^[¹³[13] Jia W, Zhao Y, Yang J, Wang W, Wang X, Ling L, et al. Simvastatin promotes dental pulp stem cell-induced coronal pulp regeneration in pulpotomized teeth. J Endod 2016; 42(7):1049-54. https://doi.org/10.1016/j.joen.2016.03.007. https://doi.org/10.1016/j.joen.2016.03.0... ^]	Soft Tissue Regeneration		Not reported	Not reported	Not reported	Not reported
	76.8 ± 4.3	47.3 ± 2.5	Not reported	Not reported	Not reported	Not reported
Iohara et al. ^[¹⁴[14] Iohara K, Murakami M, Nakata K, Nakashima M. Age-dependent decline in dental pulp regeneration after pulpectomy in dogs. Exp Gerontol 2014; 52:39-45. https://doi.org/10.1016/j.exger.2014.01.020. https://doi.org/10.1016/j.exger.2014.01.... ^]	Soft Tissue Regeneration		Not reported	Not reported	Not reported	Not reported
	60 ± 3.0	9.6 ± 2.9	Not reported	Not reported	Not reported	Not reported
Iohara et al. ^[¹⁰[10] Iohara K, Murakami M, Takeuchi N, Osako Y, Ito M, Ishizaka R, et al. A novel combinatorial therapy with pulp stem cells and granulocyte colony-stimulating factor for total pulp regeneration. Stem Cells Transl Med 2013; 2(7):521-33. https://doi.org/10.5966/sctm.2012-0132. https://doi.org/10.5966/sctm.2012-0132... ^]	Soft Tissue Regeneration		Not reported	Not reported	Not reported	Not reported
	13.5 ± 5.5	9.6 ± 2.9
	Vascularization
	3.1 ± 0.2	1.8 ± 0.3
	Neural Regeneration
	1.5 ± 0.2	0.1 ± 0.1
Zheng et al. ^[¹¹[11] Zheng Y, Wang XY, Wang YM, Liu XY, Zhang CM, Hou B, et al. Dentin regeneration using deciduous pulp stem/progenitor cells. J Dent Res 2012; 91(7):676-82. https://doi.org/10.1177/0022034512449834. https://doi.org/10.1177/0022034512449834... ^]	Dentine Regeneration		Not reported	Not reported	Not reported	Not reported
	81.4 ± 7.3	34.6 ± 4.5	Not reported	Not reported	Not reported	Not reported

	Animal Studies
Risk of Bias	Iohara et al. ^[¹⁰[10] Iohara K, Murakami M, Takeuchi N, Osako Y, Ito M, Ishizaka R, et al. A novel combinatorial therapy with pulp stem cells and granulocyte colony-stimulating factor for total pulp regeneration. Stem Cells Transl Med 2013; 2(7):521-33. https://doi.org/10.5966/sctm.2012-0132. https://doi.org/10.5966/sctm.2012-0132... ^]	Zheng et al. ^[¹¹[11] Zheng Y, Wang XY, Wang YM, Liu XY, Zhang CM, Hou B, et al. Dentin regeneration using deciduous pulp stem/progenitor cells. J Dent Res 2012; 91(7):676-82. https://doi.org/10.1177/0022034512449834. https://doi.org/10.1177/0022034512449834... ^]	El Ashiry et al. ^[¹²[12] El Ashiry EA, Alamoudi NM, El Ashiry MK, Bastawy HA, El Derwi DA, Atta HM. Tissue engineering of necrotic dental pulp of immature teeth with apical periodontitis in dogs: radiographic and histological evaluation. J Clin Pediatr Dent 2018;42(5):373-382. https://doi.org/10.17796/1053-4625-42.5.9 https://doi.org/10.17796/1053-4625-42.5.... ^]	Jia et al. ^[¹³[13] Jia W, Zhao Y, Yang J, Wang W, Wang X, Ling L, et al. Simvastatin promotes dental pulp stem cell-induced coronal pulp regeneration in pulpotomized teeth. J Endod 2016; 42(7):1049-54. https://doi.org/10.1016/j.joen.2016.03.007. https://doi.org/10.1016/j.joen.2016.03.0... ^]	Iohara et al. ^[¹⁴[14] Iohara K, Murakami M, Nakata K, Nakashima M. Age-dependent decline in dental pulp regeneration after pulpectomy in dogs. Exp Gerontol 2014; 52:39-45. https://doi.org/10.1016/j.exger.2014.01.020. https://doi.org/10.1016/j.exger.2014.01.... ^]
Selection Bias
Sequence	Yes	Yes	No	No	No
Baseline	Yes	Yes	Yes	Yes	Yes
Allocation	Unclear	No	No	No	No
Performance Bias
Random	Unclear	Unclear	Unclear	Unclear	Unclear
Blinding	No	No	No	No	No
Detection Bias
Random Outcome	No	Yes	No	No	No
Blinding	No	No	No	No	No
Attrition Bias	Unclear	Unclear	Unclear	Unclear	Unclear
Reporting Bias	Unclear	Unclear	Unclear	Unclear	Unclear
Other Bias	No	No	No	No	No

Risk of Bias		Human Trial
		Xuan et al. ^[⁴[4] Xuan K, Li B, Guo H, Sun W, Kou X, He X, et al. Deciduous autologous tooth stem cells regenerate dental pulp after implantation into injured teeth. Sci Transl Med 2018; 10(455):eaaf3227. https://doi.org/10.1126/scitranslmed.aaf3227. https://doi.org/10.1126/scitranslmed.aaf... ^]
Randomization Process		Low
Deviation from the Intended Intervention	Effect of Assignment	Low
Deviation from the Intended Intervention	Adhering to Intervention	Low
Missing Outcome Data		SC
Measuring of the Outcome		Low
Selection of the Reported Result		Low
Overall Risk of Bias		SC

[1] Author to whom correspondence should be addressed: Samira Jamal, Department of Endodontics, Stomatological Hospital, College of Medicine, Xi'an Jiaotong University, Shaanxi 710004, PR China. Phone: +86 29 82655450. E-mail: samira.jamali90@yahoo.com.

Brasil

Brasil

Dental Pulpal Tissue Regeneration, Pulpal Vitality Testing, and Healing of Apical Lesions Following Stem Cell Transplant: A Systematic Review and Meta-Analysis

Abstract

Objective:

Material and Methods:

Results:

Conclusion: