stem cell research and tissue engineering

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Stem Cell Research and Tissue Engineering

Sheila Mac Neil Professor Of Tissue Engineering and founder Director of Celltran Ltd

Ethical & legal challenges to Stem Cell research

Sheila MacNeil

University of Sheffield

Skin Forum Sheffield June 2006

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Contents

• Tissue engineering research using adult cells

Skin-burns patients

Skin-chronic ulcers

Oral mucosa-scarring of the urethra

Melanocytes-vitiligo

Corneal epithelial cells-corneal diseases

• Ethical Regulatory and Economic issues

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TMSurface engineering for delivery of epithelial cells

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TMDo we have stem cells in our cultures?

• Adult epithelial cells (skin, oral mucosa and cornea) cultured

in the laboratory contains cells with colony forming ability

which give rapid expansion

• Patients who received cultured skin in the 1980’s still doing

well-no loss of skin

• Concensus view is that culture protocols maintain a population

of cells with “stem like” properties but that without gene

manipulation these are destined to give rise to only one tissue

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A wonderful stuff is skin. It’s the stuff that keeps you in”

Spike Milligan

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10 year audit of use of CEA (Hernon et al 2006)

1 4 5 6 8 9 11 12 14 15 18 21 22 24 25 27 32 35 37 38 2 3 7 10 13 16 17 19 20 23 26 28 29 30 31 33 34 36 390

50

100

0

18

0

29

0

0

33

39

25

24

0

9

16

12

6

Patient number

Did not receive donor skin%

To

tal b

od

y su

rfa

ce a

rea

Patient number

Received donor skin

9

35

20 0

15

40

2319

54

20

0

0

30

11

0

0

12

18

14 0

120

0

0

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There had to be a simpler way to get cells to patients…

• Professor Rob Short-Surface Engineer

• Professor Sheila MacNeil-Tissue Engineer

“Lets make a post-it note for delivering skin cells to

patients” 1997

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• University of Sheffield spin-out company

• Formed 2000

• 16 staff

• MHRA approved cleanrooms in 2003

• Launched Myskin in 2004

• Merged with Xcellentis in 2006

• Raised 5 Million in funding

• Full details of development and proof of concept clinical studies with myskin Full details of development and proof of concept clinical studies with myskin

available on www.celltran.co.ukavailable on www.celltran.co.uk

Celltran Ltd

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• Autologous keratinocytes

• Proprietary materials

technology

• Chronic wounds, burns

• DFU/VLU trials

• Case studies

• Revenues since April 2004

Myskin™

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Patient Information

Thin shave biopsy taken and delivered to CellTran

Cryogenic cell storage

myskin

surface

Cell expansion at CellTran laboratory

Repeat myskin delivery as required

Wound healing

Wound bed preparation – debride and optimise*

Myskin couriered to patient

Week 0 Week 1 Weeks 2-6-2 days

myskin process

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Myskin-a cell delivery surface for keratinocytes

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USE OF MYSKIN IN ACUTE BURNS

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TMUse of Myskin for failed skin grafts Patient 5 Male, 80 years old

4 weeks non-healing Right leg before applications

After 12 applications – 78% healed, suitable for grafting

2 months post treatment

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TMUSE OF MYSKIN IN CHRONIC WOUNDS

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Single blind study with Myskin

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What types of patients can benefit ?

• Acute burns-where it provides valuable adjunct

to SSG and donor skin

• Chronic wounds-BUT-the earlier it is used the

better the outcome and the fewer applications

will be needed

• Chronic wounds of long standing may need

pretreatment to improve the wound bed prior to

application

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TMVascular surgery and amputation of toes

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TMLarval therapy and VAC therapy

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TMHoney used as an antimicrobial followed by cell therapy

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TMWound bed pre and post 2 applications of myskin

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Development a carrier surface for surgical treatment of vitiligo

Cells on carrier surfaceBiopsy

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TMTransfer of melanocytes and keratinocytes from carrier to in vitro human wound bed model

0

50

100

1stQtr

3rdQtr

East

West

North

H&

Melanoc

MTT of carrier dressing

MTT of fresh skin

S100

Melanocytes

Mel-5

Melanocytes

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Developing a coated contact lens as a carrier for cultured corneal cells for corneal diseases

Contact lens

Agar

Stroma

Sclera

Contact lens seeded with limbal epithelial cells

Organ culture

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TMTissue engineered skin and oral mucosa for reconstructive surgery

• Tissue engineered skin for release of

contractures due to earlier burns injuries

• Tissue engineered oral mucosa for

replacing chronically scarred urethral

tissue

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TMEthical, Regulatory and Economic issues

Ethical issues

• Why do this? -Because existing clinical

treatments not adequate for job

• What is the risk versus the benefit for patients?

• What can go wrong? How likely is it?

• Obtaining Ethical Committee consent

• Making sure patients are fully informed and

properly consented

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TMEthical, Regulatory and Economic issues

Ethical issues-in practice

• Patients very willing to use own tissues (small

biopsy) for burns, chronic wounds and

reconstructive surgery problems

• Ethical Committees open to research which

seeks to tackle such problems

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Regulatory issues

• Regulatory bodies react to established procedures

• Strong drive to classify work according to previous

medical technologies-is it a device? –is it a medicine?

• Tissue Engineering doesn’t fit either of above well

and is being driven towards Medicinal Products

• Running trials on autologous cell treatments not like

drug development……not a great fit…

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Regulatory issues

• UK Regulatory bodies can be approached-you

can get meetings –decisions are harder

• Real need to work closely with MHRA and HTA to

inform them of how fields are progressing

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Economic issues

• Products currently represent a small proportion of treatment cost

• New technology will increase cost of product but reduce total cost to provider

• Health economics are driving cure over treatment

Co

st o

f h

eali

ng

in

dex

Traditional ActiveAdvanced

Nursing time

Products

Other costs

Over 4 years

Source: Husing et al, 2003. The Future of Wound Care, MX (Market Analysis II) LEK Consulting, Feb 2006

UK cost per ulcer per

yearSource: Swedish Institute for Health Economics, 2000

£ 11,500

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Our philosophy of product development based on adult

autologous cells is that these should be

• Clinically effective

• Low risk for the patient

• Developed by working with clinicians and patients

• Convenient to use –streamlined delivery

We have developed a range of products and indications in

the ‘active’ sector using autologous cells

Summary

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Acknowledgements

Grateful thanks to all those patients and clinicians who have worked with us to develop tissue engineered skin products for the treatment of burns and chronic wounds.

stem cell research and tissue engineering

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