1) The document discusses using mesenchymal stem cells for alveolar bone tissue engineering to reconstruct the bone defect in cleft lip and palate patients. 2) A clinical trial was conducted with 5 patients where stem cells from deciduous dental pulp were combined with a collagen and hydroxyapatite biomaterial and grafted into the alveolar cleft region. 3) Primary outcomes included quantitative analysis using CT scans to measure bone formation before and after surgery, and qualitative analysis to observe canine eruption through the regenerated bone.

1. STEMCELL THERAPY IN CLEFT LIP AND
PALATE
Presented by :
Dr. Pratistha Singh
Clinical Research Fellow Student, AAPS, Toronto,
Canada
2015-2016
Clinical Research and Pharmacovigilance Program
Director :
Prof. Peivand Pirouzi

2. 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.

3. 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

4. STEM CELLS
EMRYONIC STEM CELLS UNIQUE FEATURES OF STEM
CELLS

5. 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 Cells
4. 2006 – Induced Pluripotent Stem Cells

6. 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

7. CLEFT LIP AND PALATE
• Congenital Defect
• Due to improper fusion
during embryogenesis.
• Can be cleft lip , cleft
palate or cleft lip and
palate

8. 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

9. 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

10. • 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

11. • 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.

12. Enrollment of subjects :
• No. of Subjects : 5
• Eligibility :
1)Age :- 7 to 12 years
2)Gender :- Both
3)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.

13. 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.

14. Primary Outcome Measures :
1)Quantitative Analysis :-
Time Frame : 6 Months
Safety Issue : Yes
Done by CT scan of alveolar cleft region pre and post-
surgery.
2)Qualitative Analysis :-
Time Frame : 3 Months
Safety Issue : Yes
Done by CT scan of alveolar cleft region after
Canine eruption

15. 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,
Misc
29.03.2015 Study Changes Protocol,
Recruitment status,
Results, Misc

16. 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 subjects
2)Sep/2013 – Extraction of deciduous teeth
3)Sep/2013 – Dental pulp was obtained
4)Dec/2013 to Jun/2014 - Alveolar Bone Graft surgery
was done.
5)After six months – Bone formation noticed

17. 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

18. SOURCES OF INFORMATION
• Stemcells.nih.gov
• Medicalnewstoday.com
• Wikipedia.org