STEM CELL THERAPY IN CLEFT LIP AND PALATE

Presented by : Dr. Pratistha SinghClinical Research Fellow Student, AAPS, Toronto, Canada2015-2016

Clinical Research and Pharmacovigilance Program Director : Prof. Peivand Pirouzi

CONTENT

• Stem cells : Introduction and their therapeutic use.

• Cleft lip and Palate : An insight into the congenital disorder.

• Clinical trial : Stem cell induced alveolar bone tissue engineering in the cleft lip and palate patients.

STEM CELLS : INTRODUCTION

• Stem cells are undifferentiated biological cells that can differentiate into specialized cells and can divide (through mitosis) to produce more stem cells.

• Found in multicellular organisms.• In mammals, 2 types :- 1) Embryonic stem cells 2) Adult stem cells

STEM CELLSEMRYONIC STEM CELLS

UNIQUE FEATURES OF STEM CELLS

HISTORY OF STEM CELLS

1. 1960 – U of T , Ernest A Mcculloch and James E. Till.

2. 1981 – Embryonic stem cells from early mouse embryo.

3. 1998 – Human Embryonic Stem Cells4. 2006 – Induced Pluripotent Stem Cells

STEM CELL THERAPY

• Stem cell therapy is the usage of stem cells in the treatment or prevention of a disease or condition.

• Disadvantages:-1. Immunosuppression.2. Pluripotency unwanted cells tumors

CLEFT LIP AND PALATE

• Congenital Defect• Due to improper fusion

during embryogenesis.• Can be cleft lip , cleft

palate or cleft lip and palate

TYPES OF CLEFT LIP AND PALATE

CLEFT LIP CLEFT PALATE

Unilateral incomplete

Unilateral complete

Bilateral complete

Incomplete cleft palate

Unilateral complete lip and palate

Bilateral complete lip and palate

CLINICAL TRIAL RELATING THE INTERVENTION WITH THE CONDITION

• Official title : Use of Mesenchymal Stem Cells for alveolar bone tissue engineering for cleft lip and palate patients.

• ClinicalTrials.gov Identifier : NCT01932164

• Sponsor : Hospital Sirio-Libanes, Brazil

• Collaborator : Hospital Infantil Universitario Niño Jesús, Madrid, Spain

• Information provided by (Responsible Party) / Principal Investigator :

Daniela Franco Bueno, DDS, PhD, Hospital Sirio-Libanes

• Study Start date : May 2013

• Estimated Study completion Date : March 2016

• Primary Completion Date : March 2015

• Study First Received : August 27, 2013

• Study Last Updated : March 18, 2015

• Study Last Verified : August 2013

• Study Type : Interventional

• Study Design : Endpoint classification : Efficacy study

Intervention Model : Single group assignment Masking : Open label

Primary Purpose : Treatment

• Health Authority : National committee of Ethics in Research, Brazil

• Purpose : The aim of this study is to perform the bone tissue engineering to reconstruct the alveolar bone defect in cleft lip and palate patients using mesenchymal stem cells from deciduous dental pulp associated with a collagen and hydroxyapatite biomaterial (Geistlich Bio-Oss®) through prospective qualitative and quantitative analysis of bone neoformation.

Enrollment of subjects :

• No. of Subjects : 5

• Eligibility :1)Age :- 7 to 12 years2)Gender :- Both3)Healthy Volunteers :- No

• Inclusion Criteria :1)Diagnosis of unilateral cleft lip and palate ;

2)Patient who has performed the treatment to align the dental; 3)Patient who has 2/3 of the root of the canine tooth formed.

• Exclusion Criteria : 1)Prior alveolar surgery;

2)Canine teeth erupted before the bone graft; 3)Presence of co-morbidities; 4)Incomplete documentation; 5)Patients who have not done all the multidisciplinary treatment.

Detailed Description of the Study :

• The reconstruction of the craniofacial skeleton in development between 2 and 10 years old, remains a major challenge for reconstructive plastic surgery.

1)Local bone unavailable 2)Significant morbidity. 3)Alloplastic material incompatible.

• The association of mesenchymal stem cells to biomaterials – a potential solution.

• The aim of this study is to perform the bone tissue engineering using mesenchymal stem cells with a collagen and hydroxyapatite biomaterial (Geistlich Bio-Oss®) through prospective qualitative and quantitative analysis of bone neoformation.

Primary Outcome Measures :

1)Quantitative Analysis :-Time Frame : 6 MonthsSafety Issue : YesDone by CT scan of alveolar cleft region pre and post- surgery.

2)Qualitative Analysis :-Time Frame : 3 MonthsSafety Issue : YesDone by CT scan of alveolar cleft region after Canine

eruption

HISTORY OF NCT01932164 :

• Record State : Released

UPDATED VIEW TYPE OF INFO CHANGED

29.08.2013 Study Nothing (Earliest Version on Record)

30.08.2013 Study Changes Protocol, Administrative,

Misc29.03.2015 Study Changes Protocol,

Recruitment status, Results, Misc

HISTORY continued :

• Participant Flow :Recruitment Details :

*5 patients *Between June and August 2013

• Pre-Assignment Details :No text entered

• Series Of Events :1)Aug/2013 – Recruitment of subjects2)Sep/2013 – Extraction of deciduous teeth3)Sep/2013 – Dental pulp was obtained4)Dec/2013 to Jun/2014 - Alveolar Bone Graft surgery

was done.5)After six months – Bone formation noticed

HISTORY Continued :

• Serious adverse Events : No text entered

• Other adverse Events : No text entered

• Limitations and caveats : No text entered

• More Information : Certain Agreements - All principal investigators are employed by the organization sponsoring the study

• Point of Contact : Name /Title : Daniela Franco Bueno / PI Organization :- Hospital Sirio , Libanes Contact :- +5511997900159 dbuenousp@gmail.com

SOURCES OF INFORMATION

• Stemcells.nih.gov• Medicalnewstoday.com• Wikipedia.org