Transcript Clinical trials

Manifestation of Novel Social Challenges of the
European Union
in the Teaching Material of
Medical Biotechnology Master’s Programmes
at the University of Pécs and at the University
of Debrecen
Identification number: TÁMOP-4.1.2-08/1/A-2009-0011
Manifestation of Novel Social Challenges of the
European Union
in the Teaching Material of
Medical Biotechnology Master’s Programmes
at the University of Pécs and at the University
of Debrecen
Identification number: TÁMOP-4.1.2-08/1/A-2009-0011
Dr. Judit Pongrácz
Three dimensional tissue cultures and
tissue engineering – Lecture 23
CLINICAL TRIALS (1)
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Definition of a clinical
trial
Health related research studies
performed in human beings
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Types of clinical trials
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Treatment trials
Prevention trials
Diagnostic trials
Screening trials
Quality of life trials
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Participants in a clinical
trial
• To gain access to novel research
treatment
• Provide information on drug efficacy
and potential toxicity
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Benefits of taking part in
a clinical trial
• Gain access to novel therapies
• Obtain expert medical care
• Contribution to medical research
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Risks of clinical trials
• Unpleasant or life-threatening side
effects
• The experimental treatment may not be
effective
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Process of clinical trials
• Based on research results
• Based on a specific protocols
• Participants are continuously
monitored
• Results assessed and statistics are
performed
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Phases of clinical trials
• Phase I – small group of people (2080)
• Phase II – larger group of people
(100-300)
• Phase III –large group of people
(1000-3000)
• Phase IV – marketing studies
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Stem cell therapy and
clinical trials
Hematopoietic stem cell transplantation
is the first stem cell based therapy
strategy that has gone into clinical
trials
Stages to reach a
marketable cell-based
therapeutic product
Research
Animal tests
Marketable
product
Production
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Clinical
trials
Phase I, II, III,
Market
research
Manifestation of Novel Social Challenges of the
European Union
in the Teaching Material of
Medical Biotechnology Master’s Programmes
at the University of Pécs and at the University
of Debrecen
Identification number: TÁMOP-4.1.2-08/1/A-2009-0011
Dr. Judit Pongrácz
Three dimensional tissue cultures and
tissue engineering – Lecture 24
CLINICAL TRIALS (2)
Clinical trials for
cellular therapy of liver
failure
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• Autologous BMSC – not ready for
routine clinical therapy
• Differentiated BMSC using HGF
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Liver dialysis
• Ammonia causes encephalopathia
• Extracorporeal detoxification
• Dialysis-like solutions
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Bioartificial liver
Oxygen
Plasma
filter
Bioreactor
PKM-19 Liver cells
Patient’s
plasma
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ELAD® bioartificial liver
Incubator
Blood circuit
Ultrafiltrate circuit
Glucose
Heparin
ELADTM
infusion
Blood pump
Ultrafiltrate
pump
Pumping
system
ELADTM
Cell filter
Oxygenator
ELADTM
Plasma
filter
ELADTM
Recirculation
pump
Reservoir
Priming
infusion
line
Glucose
infusion
pump
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Cell-free ELAD: MARS
Blood circuit
MarsFlux
Dialyzer
Mars-Albumin
circuit
Dialysate
circuit
diaMarsFlux
Adsorption columns
diaFlux
Dialyzer
Blood
pump
Anion
exchange
resin
Activated
charcoal
Albumin
pump
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Skin grafting and
replacement
• Burn injuries
• Chronic wounds, e.g. diabetic or PAD
ulcers
• Cosmetic surgery
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Structure of the skin
Stratum corneum
Stratum lucidum
Stratum
granulosum
Stratum mucosum
Hair
Sebaceous gland
Erector pili muscle
Epidermis
Stratum
germinativum
Dermis
Sweat gland
Artery
Fat
(Adipose tissue)
Nerve
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Purpose of skin grafting
• Restore the barrier functionkeratinocytes
• Recently no nerve, vascular, sweat
glans or hair follicles can be
included into tx skin
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Skin grafts
• Full thickness burns - dermis and
epidermis are both lost
• Partial thickness burns - epidermis is
largely intact
• If more, than 30-40% body surface is
burnt
• Smaller surface burns may be cured
with split thickness autografts
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Autologous skin grafts
Skin is meshed to
cover a large wound
Graft taken from
patient’s
healthy skin
Wound
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Cultured Epithelial
Allograft (CEA) I
• CEA alone
• Intagra combined with CEA
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Cultured Epithelial
Allograft (CEA) II
Transplantation of
autologous cultured
epidermis
Patient
Grafting
Injured area
Skin biopsy
Skin specimen
Sheet formation
Culture
Cell seeding/
Inoculation
Isolation of
keratinocytes
Feeder cells
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Tissue engineered skin
methodology
Enzymatic
segregatio
n
Epidermis
Dermis
9x
P2
24hr
Enzymatic removal of
3T3s
Feeder 3T3
fibroblast
s
Isolation of
keratinocytes
9x
P2
Proliferation and
differentiation of
multilayer epithelial
sheets
P0
Medium change
9x
P0
P1 The epithelial sheets are removed for clinical use
Tissue engineered skin
products available for
clinical use
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Type
Products
Epidermal cover
• CEpicell (Genzyme) –cultured epitermal sheets
• Epidex (Modex Therapeutics)- epidermal sheets
from hair biopsies
• Myskin (CellTran)- cells in a synthetic carrier
• C3- cells in a spray
• Cultured allogenic keratinocytes
• Cultured autologous keratinocytes
Dermal replacement
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Epidermal/dermal
replacement
• Permaderm (Cambrex)
• Apligraf (Novartis)
• Orcel (Ortec International)
Integra (Integra)
Alloderm (Lifecell)
Permacol (Tissue Science Labs)
Dermagraft (Advaced BioHealing)
Transcyte (Advanced BioHealing)