1. Prof. Lee Ann Laurent-Applegate
Department of Musculoskeletal Medicine (DAL)
Reconstructive and Plastic Surgery (CPR)
Unit of Regenerative Therapy (UTR)
University Hospital of Lausanne, Switzerland

2. Summary
• Cell Therapies and New Regulations
– Legal and Regulatory Issues
• Selection of Cell Types in Tissue Bioengineering
• Advances and Uses of Progenitor Cells in Burn
and Wound Treatments

3. Transplantation Law: Switzerland
1st July, 2007

4. Regulatory Agencies
• Medications –human
• Medications -veterinary
• Alimentary Complements
and phytotherapy
• Drugs
• Blood and derivatives
• Hygenic Articles
• Transplants

5. Regulatory Affairs: Cellular products

6. Progenitor Cell Transplantation
Program
Prof. Lee Ann Laurent-Applegate Prof. Wassim Raffoul
Mme Jeanne-Pascale Simon Directrice of Program Co-Directeur of Program
Lawyer-CHUV Cellular Therapy Unit, DAL, CHUV
1 single organ donation Master Cell Bank
(skin 2 cm2) Frozen –165°C
Program registered with OFSP and Swissmedic since 1993

7. New Federally Registered Program:
« Clinical Progenitor Cell Banks »
• Began May, 2008
• Organ donation: Musculoskeletal Tissues
- Skin - Bone - Cartilage
- Disc - Muscle -Tendon
08.2007, protocole #62/07:
Développement de banques cellulaires fœtales pour ingénierie tissulaire

8. GMP in regenerative medicine
– Buildings and facilities
– Organization, personnel, training, evaluation
– Equipment, reagents and supplies
– Procedures
– Production and process controls
– Finished product control
– Laboratory controls
– Records and reports

9. Primary Tissue/Cell culture
cGMP
Tracing of Tissue Materials & Media Equipment
Incubators Liq N2–165°C

10. CHUV: BH05/516 : Validated Processing
of ”Clinical Progenitor Cell Banks”
Clean Rooms dedicated to Progenitor Cells: cGMP

11. Summary
• Cell Therapies and New Regulations
– Legal and Regulatory Issues
• Selection of Cell Types in Tissue Bioengineering
• Advances and Uses of Progenitor Cells in Burn
and Wound Treatments

12. Cells Types for Cell Therapy
Embryonic Stem Embryonic Fetal Fetal Adult Stem
0-2 weeks 5-8 weeks 9-14 weeks
High manipulation High manipulation
 High needs in nutrients  Differentiated cells  Uncertainty for
 Problems in uniformity  Easy to handle differenciation
 Uncertainty in differenciation  No need of nutrients  High nutritional needs
 Tumorigenecity  Problems of uniformity
< 100 cells < 100 cells High Number of cells ~1 cell/ 104-5

13. Progenitor Fetal Cells: Historical Use
Progenitor Cells
1930 Polio Vaccine
1954 Nobel Prize of medicine
1964 - 66
• Fetal Cells MRC-5:
polio, hepatitis A, chicken
Not the same as stem cells pox, measles, rabies
• Differentiated Cells
• No specific growth factor needs
• Fetal Cells WI-38:
mumps vaccine (RA 27/3)

14. Cellular Therapy/Tissue Engineering
Cell type Compatible Matrix Patient Delivery
+
⁼
Patient cells
Stem cells CE marked matrix
Easy usage
Progenitor Fetal Cells for clinical studies
Animal cells

15. Adult Stem Cells
Autologous (Hair Follicle: Epidex®)
Treatment of chronic wounds by adult stem cells from hair bulb
Delay: 6 - 8 weeks Modest size 1 cm2 Problems in out-scaling
But…
Treatment 4 weeks Vac
18 x Epidex
24 x Epidex
Cost: 12,095 USD

16. Skin Substitutes
(Foreskin-Apligraft®)
Newborn organ donations (foreskin tissues)
7.5 cm
~1,960.- USD for each 7.5 cm

17. Cell Therapy: Why ?
• Not enough tissue
• Not rapid enough

18. Skin Substitutes : Possible for our
burn patients (50%) ?
Apligraf® Epidex ®
~1,960.- USD ~6,280.- USD
for 7.5 cm (x1) for 1.0 cm (18x)
~261,472.- USD ~ 3,529,857.- USD

19. Necessity for Skin Replacements
Transplantation of skin
- Burns: 1,500 hosp./yr Swiss
A real need! CHUV burn center 400,000 cm2/yr
- Wounds
1% general population
20% > 80 years
2-4% health costs/1.2-2.4 billion (European wound management, 2010)

20. Summary
• Cell Therapies and New Regulations
– Legal and Regulatory Issues
• Selection of Cell Types in Tissue Bioengineering
• Advances and Uses of Progenitor Cells in Burn
and Wound Treatments

21. Primary Tissue/Cell culture

22. Potential of One Organ
Donation for Burn Treatment
CHUV BH 05
Testing:
Mother Donor: Serology, 1 & 3 months
Fetal Tissue: Pathology, Autopsy &
individual tissues, Karoytype
Organ donation
Primary cell culture
1 Parental
Cell Bank (PCB)
Stored at -165°C

23. Potential of One Organ
Donation for Burn Treatment
CHUV BH 05 Bioreliance, Glasgow
Testing:
Mother Donor: Serology, 1 & 3 months
Fetal Tissue: Pathology, Autopsy &
individual tissues, Karoytype
Organ donation
Master Cell Bank
~300 vials@ 10 x 106 cells
Stored at -165°C
Primary cell culture
1 Parental
Cell Bank (PCB)
Stored at -165°C

24. Potential of One Organ
Donation for Burn Treatment
CHUV BH 05 Bioreliance, Glasgow
Testing:
Mother Donor: Serology, 1 & 3 months
Fetal Tissue: Pathology, Autopsy &
individual tissues, Karoytype
Organ donation
Master Cell Bank
~300 vials@ 10 x 106 cells
Stored at -165°C
Primary cell culture
1 Parental
Cell Bank (PCB)
Stored at -165°C Working Cell Bank
~300 vials@ 10 x 106 cells
Stored at -165°C

25. Potential of One Organ
Donation for Burn Treatment
CHUV BH 05 Bioreliance, Glasgow CHUV, Clinical Trial
Testing:
Mother Donor: Serology, 1 & 3 months
Fetal Tissue: Pathology, Autopsy &
individual tissues, Karoytype
cGMP WCB vial
Organ donation
Master Cell Bank Direct seeding onto
~300 vials@ 10 x 106 cells collagen matrix
Stored at -165°C
Primary cell culture
1 Parental ~35 x 109 Treatments
Cell Bank (PCB)
Stored at -165°C Working Cell Bank
~300 vials@ 10 x 106 cells Global Cost ~ 1-2 million USD
Stored at -165°C

26. Capacity of the GMP Cell Bank
Optimiztion of Biobank:
35,000,000,000 (9 x 12 cm)

27. Lausanne Trial
2000-2005
• Burns
• Acute and Chronic Wounds
Goal:
Reduce surface for autografting

28. Lausanne Trial
10 patients with burns
1 2 3 4 5
After 2
weeks
After 1.5 mo 18 mo 9 mo 13 mo 18 mo
www.thelancet.com Vol 366 September 3, 2005

29. Lausanne Trial:
Key elements
• Progenitor cells capable of skin regeneration
– Not a «graft »
– Stimulation of Patients own cells to regenerate
correctly
– Hair follicles and sebaceous glands present in
regenerated patient skin

30. Lausanne Trial
www.thelancet.com Vol 366 September 3, 2005

31. Use of MCB and WCB
1. cadaver skin replacement
Replace cadaver skin

32. Skin in a Box:
“First Cover”
porcine
• Transmission
diseases
• Conservation: fresh,
frozen, glycerol
• Infections
Technique more “clean”

33. Use of WCB and MCB
2. Treatment of Donor Graft Sites

34. Use of WCB and MCB
3. Treatment of Mesh Graft Sites
Mesh Grafting
• Increase graft “take”
• Diminish graft dehydration

35. Innovative Therapies
- Reduction of costs
- Diminish time hospitalization
- Diminish time care (bandages)
- Diminish subsequent surgeries
- Simplicity
- Universality
- Efficacity

36. Medical doctors:
Prof. Wassim Raffoul
Prof. Brigitte Jolles-Haeberli
Anthony de Buys Roessingh, MD, PhD
Senior Scientists Prof. Dominique Pioletti
Nathalie Hirt-Burri, PhD
Claude Schweitzer, PhD
Technicians
Corinne Scaletta
Sandra Jaccoud
Murielle Michetti Prof. Brigitte von Rechenberg
Doctoral Students:
Salim Darwiche, MSE
Anthony Grognuz, MSPh
Dr Jean-François Bauen
Interns:
Lina Deghayli
Sara Moufarrij
Lawyer
Jeanne-Pascale Simon, JD

37. Thank you Sir Roger & Lady Kristina

38. Making of…

39. Making of…