Use of Mesenchymal Stem Cells for Alveolar Bone Tissue Engineering for Cleft Lip and Palate Patients

• ClinicalTrials.gov Identifier: NCT01932164
• Recruitment Status: Completed
• First Posted: August 30, 2013
• Results First Posted: March 30, 2015
• Last Update Posted: May 28, 2020
• Sponsor: Hospital Sirio-Libanes
• Collaborator: Hospital Infantil Universitario Niño Jesús, Madrid, Spain
• Information provided by (Responsible Party): Daniela Franco Bueno, Hospital Sirio-Libanes

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Cleft Lip and Palate
• Interventions: Procedure: maxillary alveolar graft by tissue engineering; Procedure: Bone tissue engineering using mesenchymal stem cells
• Enrollment: 5

Participant Flow

Recruitment Details	the recruitment of 5 patients was performed at dentistry department of Hospital Menino Jesus between june and august 2013.
Pre-assignment Details

Arm/Group Title	Cleft Lip and Palate
Arm/Group Description	Patients with cleft unilateral lip and palate that have already performed the alignment of dental arches through the recommended orthodontic treatment maxillary alveolar graft by tissue engineering: Extraction of deciduous tooth of cleft lip and palate patients to obtain mesenchymal stem cells; Secondary graft by bone tissue engineering using mesenchymal stem cell obtained from dental pulp of deciduous teeth (autogenous) associated with a biomaterial composed of collagen and hydroxyapatite.
Period Title: Overall Study
Started	5 [1]
Cleft Lip and Palate	5 [2]
Cleft Lip and Palate	5 [3]
Cleft Lip and Palate	5 [4]
Cleft Lip and Palate	5 [5]
Cleft Lip and Palate	5 [6]
Completed	5 [7]
Not Completed	0
[1] It was performed the selection of 5 patients to participate of these study (08/2013); [2] It was performed de extraction of deciduous teeth of 5 cleft lip/palate patients (09/2013); [3] Dental pulp was obtained from teeth of 5 different patients (09/2013); [4] Mesenchymal stem cell obtained from dental pulp of 5patients was obtained, caractherized and frozen; [5] Alveolar bone graft surgeries were did using their dental pulp stem cells with biomaterial; [6] The surgeries were performed between december 2013 and june 2014.; [7] In all 5 patients we observed bone formation closing the alveolar cleft after 6 months

Baseline Characteristics

Arm/Group Title		Cleft Lip and Palate
Arm/Group Description		5 Patients with cleft unilateral lip and palate that have already performed the alignment of dental arches through the recommended orthodontic treatment will be selected to be submited to alveolar bone tissue engineering surgery maxillary alveolar graft by tissue engineering: Extraction of deciduous teeth of cleft lip and palate patients to obtain mesenchymal stem cells; Bone tissue engineering using mesenchymal stem cells: Secondary alveolar graft in patients with cleft lip and palate using using mesenchymal stem cell obtained from dental pulp of deciduous teeth (autogenous) associated with a biomaterial composed of collagen and hydroxyapatite.
Overall Number of Baseline Participants		5
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	5 participants
	<=18 years	5 100.0%
	Between 18 and 65 years	0 0.0%
	>=65 years	0 0.0%
Sex: Female, Male [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	5 participants
	Female	3 60.0%
	Male	2 40.0%
		[1] Measure Description: 3 female and 2 male children with cleft lip and palate were submited to bone tissue engineering alveolar bone graft.
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
Brazil	Number Analyzed	5 participants
		5

Outcome Measures

1. Primary Outcome

Title	Amount of New Bone Mass Formed
Description	The quantification of bone formation will be conducted by analysis of CT scans of alveolar cleft area that receive autogenous mesenchymal stem cells from dental pulp associated with the biomaterial 3 and 6 months after surgical procedure ( tissue engineering ) in comparison with CT Scan previously of tissue engineering surgery.Preoperative and follow-up examinations reveled progressive alveolar bone union in all patients. For these 5 patients final completion of the alveolar defect with an 89,5% mean bone height was detected 6 months postoperatively. We are still waiting the canine dental eruption at the new bone. For these group of patients the bone tissue engineering using autologous mesenchymal stem cells associated with biomaterial resulted in satisfactory bone healing.
Time Frame	6 months from surgical procedure for alveolar grafting;

Outcome Measure Data

Analysis Population Description

3 females and 2 males with cleft lip and palate

Arm/Group Title	Cleft Lip and Palate
Arm/Group Description:	Patients with cleft unilateral lip and palate that have already performed the alignment of dental arches through the recommended orthodontic treatment maxillary alveolar graft by tissue engineering: Extraction of deciduous tooth of cleft lip and palate patients to obtain mesenchymal stem cells; Secondary graft by bone tissue engineering using mesenchymal stem cell obtained from dental pulp of deciduous teeth (autogenous) associated with a biomaterial composed of collagen and hydroxyapatite.
Overall Number of Participants Analyzed	5
Mean (95% Confidence Interval); Unit of Measure: percentage of bone formation
	89; (89 to 100)

2. Primary Outcome

Title	Quality of Bone Regeneration
Description	The quality of bone formation will be conducted by analysis of CT scans of alveolar cleft area through canine tooth eruption in these position of new bone formation by tissue engineering techniques. We are waiting the canine eruption at the mouth.
Time Frame	Three months after the graft

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cleft Lip and Palate
Arm/Group Description:	Patients with cleft unilateral lip and palate that have already performed the alignment of dental arches through the recommended orthodontic treatment maxillary alveolar graft by tissue engineering: Extraction of deciduous tooth of cleft lip and palate patients to obtain mesenchymal stem cells; Secondary graft by bone tissue engineering using mesenchymal stem cell obtained from dental pulp of deciduous teeth (autogenous) associated with a biomaterial composed of collagen and hydroxyapatite.
Overall Number of Participants Analyzed	5
Mean (80% Confidence Interval); Unit of Measure: percentage of bone filling
	90; (80 to 100)

Adverse Events

Time Frame	The adverse event data were collected on days 15th, 1 month, 6 months and 12 months of all 5 patients.
Adverse Event Reporting Description	All adverse event information used by clinical trial were used.
Arm/Group Title	Cleft Lip and Palate
Arm/Group Description	5 Patients with cleft unilateral lip and palate that have already performed the alignment of dental arches through the recommended orthodontic treatment maxillary alveolar graft by tissue engineering: Extraction of deciduous tooth of cleft lip and palate patients to obtain mesenchymal stem cells; Secondary graft by bone tissue engineering using mesenchymal stem cell obtained from dental pulp of deciduous teeth (autogenous) associated with a biomaterial composed of collagen and hydroxyapatite.
All-Cause Mortality
	Cleft Lip and Palate
	Affected / at Risk (%)
Total	0/5 (0.00%)
Serious Adverse Events
	Cleft Lip and Palate
	Affected / at Risk (%)
Total	0/5 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Cleft Lip and Palate
	Affected / at Risk (%)
Total	0/5 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Dra Daniela Franco Bueno
• Organization: Hospital Sirio Libanes
• Phone: +5511997900159
• EMail: dbuenousp@gmail.com

Publications:

Hibi H, Yamada Y, Ueda M, Endo Y. Alveolar cleft osteoplasty using tissue-engineered osteogenic material. Int J Oral Maxillofac Surg. 2006 Jun;35(6):551-5. doi: 10.1016/j.ijom.2005.12.007. Epub 2006 Apr 11.

Gimbel M, Ashley RK, Sisodia M, Gabbay JS, Wasson KL, Heller J, Wilson L, Kawamoto HK, Bradley JP. Repair of alveolar cleft defects: reduced morbidity with bone marrow stem cells in a resorbable matrix. J Craniofac Surg. 2007 Jul;18(4):895-901. doi: 10.1097/scs.0b013e3180a771af.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Tanikawa DYS, Pinheiro CCG, Almeida MCA, Oliveira CRGCM, Coudry RA, Rocha DL, Bueno DF. Deciduous Dental Pulp Stem Cells for Maxillary Alveolar Reconstruction in Cleft Lip and Palate Patients. Stem Cells Int. 2020 Mar 12;2020:6234167. doi: 10.1155/2020/6234167. eCollection 2020.

• Responsible Party: Daniela Franco Bueno, Hospital Sirio-Libanes
• ClinicalTrials.gov Identifier: NCT01932164
• Other Study ID Numbers: HSL 2013-04
• First Submitted: August 27, 2013
• First Posted: August 30, 2013
• Results First Submitted: March 18, 2015
• Results First Posted: March 30, 2015
• Last Update Posted: May 28, 2020