Professional Documents
Culture Documents
1.
2.
3.
4.
5.
6.
1. :
a.
b. :
c .
d. :
2. :
3.
4.
3
1999
2001a
4~5,000
4~5,000
2000
2004
1999
2003c
2004d
2005f
2006
a. 200310;
d. UONS/11.20. 2004;
g. UNOS/Jan 14th 2006;
90
120
181
195
3,981
6,774
63,000
83,432
87,268d
91,432
94,757g
8,802
9,433e
13,333
12,394h
17,000
16,984
18,108e
25,952
24,435h
1. :
2. :
1. :
2. :
4.
3.
1.
2.
hDAF
1.
31
2.
78
3.
(2000)
11
HAL-DP A1+B1
HAL-DQ A1+B1
HAL-DR A1+B1
Y113-7&-8
Y122-02A
D146-13A
85/10/18 /
88/4/21
89/4/30
Y62-11A
Y25-12A
Y25-11A
Y25-13A
Y280-11A
Y15-11A
Y69-10a
91/02/21
92/1/23
91/01/18
91/01/18
91/09/23
92/1/16
93/3/10
Actin-hDAF
hDAF/hHO-1
hHO-1/GFP
12
Resistance
Pressure Sensor
Connecting
Needle
A
U
Isolated
Kidney
Pump
Holding
Funnel
Outlet
Reservoir
O2 and Heat
Filtrated
Collection
Volume Adjustment/
Blood Introduction
Saline perfusion
Saline perfusion
14
Tg/B(931005)
15
Tg/O (931005)
Tg/A(930929)
SENSTIZATION
Donor
kidney
Passenger leukocyte
Class II MHC
antigen
TH
TH
TH
TH
IL-2
CTL
CTL
CTL
Effector
Lymph node
HLA-DP Tg Pigs
Responder: HLA DPw4(+) human lymphocyte
*
1
0.95
n=4
0.9
SI
0.85
n=4
n=4
0.8
0.75
Human DP4(-)
TG
NTG
Stimulators of MLC
HLA-DQ Tg Pigs
2
1.8
1.6
1.4
1.2
Responder
Human (DQw3-)
0.8
0.6
0.4
0.2
0
18
Human
NP
NTG
TG
Stimulators
1.6
1.4
1.2
Responder
0.8
Human (DQ+)
0.6
0.4
0.2
0
Human
NP
NTG
TG
Stimulators
*
120
100
80
Responder
60
Human DQw3(-)
40
20
0
Human
NP
TG
Stimulators
*
160
140
120
100
Responder
80
60
Human DQw3(+)
40
20
0
Human
NP
TG
Stimulators
Conclusion
This similarity of MHCII between pig and
human by the HLA transgenic pig can help
to reduce the xenogenic cellular response
between human and pig.
Ching-Fu Tu, C.-J. Lee, J. M. Lee, K. Tsuj.
2003. Transgenic swine having HLA-D gene,
swine cells thereof and xenografts there from.
(US 6,639,122 B1/ Patent)
22
Beyond
hyperacute
rejection ?
Complement
How many transgenes would you like
Actin-hDAF
to put into my genome?
Natural Ab
23
1,3-GT KO
SLA
DXR?
HO-1
HAR
HLA-II
Genes
knock out
(Cloning pigs)
Cellular-mediated
SLA-I and II ?
HAL-DR
HLA-DQ
HLA-DP
Fas-L?
HLA-I
1()
24
hHO-1/GFP
25
1. Chapman et al., N. Eng. J. Med. 333: 1498-1501. (1995)
2. Patience et al., Nature Med. 3:282-286. (1997)
PK-15
3. Le Tisser et al., Nature 389: 681-682. (1997)
Two sets of human-tropic pig retrovirus. (PERV-A &-B)/PK-15
4. Wilson et al., J. Virol. 72:3082-3087. (1998)
Retrovirus released from porcine primary peripheral blood
mononuclear cells infects human cells.
5. Luc et al., Nature 407:90-94. (2000)
(Xenotransplantation, 2007)
26
27
A A
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