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Xenotransplantatio
0
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وال رل ود اتف
replacing damaged or
destroyed cells in
تسوت ت۱۳
۲5 ,01206165
and Parkinson's disease
‘Bridging transplants
- providing organ
function externally to
patients with organ
failure.
iXenotransplantation|
*Organ transplants -
replacing diseased
organs, such as heart,
lungs, liver, pancrease
and kidneys.
وا یل وت از وه
skin grafts, cornea
transplants or bone
transplants.
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econnecting blood vessels for organ transplants
mune system causes transplant rejection
oon kidney transplant enotransplantation in Asia
Baboon to human bone marrow transplant for HI
I human to human transplant
Clinical trials of pig cell transplants continue
Worldwide ban on all xenotransplantation
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e is xenotransplantation research taking p
این
eae
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known pathogens of humans (e.g.,
Mycobacterium tuberculosis and rabies
virus)
human hosts (e.g., Toxoplasma gondii and
known pathogens of immunocompromised |
Salmonella spp.)
pathogens of transplant recipients (e.g.,
microbes similar to those recognized to be |
(ك5ناألا30ع30 300 كناءأناه اهنع جرمغلء عواعومم
and دلیف (e.g., ده 03 نط مرمععءم
rotavirus)
{viruses with high a _ capacity for
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donors and xenogenic
7 a) LES ۳
chimpanz baboon
حت
Xenogenic organs
1)Heart 2)kidney 3)Liver
4)Lunags
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INACTIVE PROVIRUS POTENTIAL ACTIVATION
Potential porcine endogenous
retrovirus activation Porcine
endogenous retrovirus (PERV) is a
retrovirus found in the DNA of all
ور ار ۱۱۰/2
inactive proviral form, but can
potentially produce mature viral
particles infectious for other
species. PERV infection is a risk of
pia to human transplants
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rapidly, often before the surgery is
complete, 25 pre-existing
antibodies from the immune
9 2507 ۳
Acute rejection - occurs in first
Aiton tte Lies melee [18 ed
)
develops
Chronic rejection - occurs
gradually over several years after
كد
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‘Acute humoral xenograft rejection
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Xenotransplantation advantages over allotransplantation
it offers a
virtually
unlimited
source of
scheduling is not
dependent on the
unpredictable availability
of a donor human organ,
allowing for both
advance planning and
the interntionally timed
harvesting of an organ
for immediate
transplantation as well g
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10
Reveet euly2018 | Accepies: 20 uly 2018
BRIEF COMMUNICATION witey
Pig tracheal patchy xenotransplantation in the dog
Tae-Ki Lee’ | Jong-Min Kim?? @ Seok Hwa Choi?
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Method
recipients: Three healthy beagle dogs (8-9 kg)
donor: one pig (20 kg)
a pig cartilaginous tracheal patchy (2 x 2 cm half tube) was sutured to the
tracheal resected site in each dog
immunosuppression: Antithymocyte globulin (2.5 mg/kg infusion, DO and
1), tacrolimus (4.5 mg/kg, twice a day for 2 months), and
methylprednisolone sodium succinate (1 mg/kg, IV, for 2 days and
tapering)
The levels IL-2 and IFN-y in the serum were measured at DO, 7, and 28
Tracheoscopy was performed at D28, 60, and 90
the expression of dog and pig genes in the graft was evaluated by PCR
Histopathological examination of the graft was conducted.
11
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D METHODS
imental animals, harvesting pig trachea, and
ical procedures for pig tracheal patchy apposition
+ Three healthy beagle dogs (age; 1 year, male, 8-9 kg) were used as
recipients
* a wild-type pig (age; 2 months, male, 20 kg) was used as the donor
+ The pig was sacrificed following a protocol approved by Institutional
Animal Care and Use Committee (IACUC), and the trachea was
harvested aseptically and placed in sterilized bottles. The cartilaginous
tracheal patchy of the harvested tissue was trimmed to 2 x 2 cmina
half-tube shape
| + Pig tracheal patchy apposition within the resected site was performed
with a simple interrupted suture using absorbable monofilament suture
۹۹ (5-0 PDS, Ethicon, UK), and the wound was closed in the usual fashion.
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red antithymocyte globulin (2.5 mg/kg, IV, DO and D1;
‘yme, Cambridge, MA), tacrolimus (4.5 mg/kg, PO, twice a day for
‘af, Astellas Pharma Korea, Seoul, Korea), and methylprednisolone
‘cinate (1 mg/kg, IV, DO and D1; Primedrol inj 125 mg, Jeilpharm, Seoul,
Tracheoscopic examination
A tracheoscopy was performed at D28, 60, and 90 under general anesthesia. The
mucosal surface of the pig tracheal patchy was examined, and no biopsy sample was
ie) <a
2.4 Quantification of the serum interleukin-2 (IL-2) and
interferon-y (IFN-y)
2.5 Gene evaluation of the pig 16S and the dog cytochrome b in
the graft
2.6 Primer design
| 2.7 PCR
2.8 Histological examination 4
زع
Alecia ay
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RESULTS
3.1 Serum IL-2 and IFN-y levels
The levels of the serum IL-2 and IFN-y at D7 were significantly higher than those at DO
and 28 (P< 0.05)
The levels of IL-2 and IFN-y in the peripheral blood at DO, 7, and 28. The levels of
serum IL-2 and IFN-y at D7 are significantly higher than are those at DO and 28
\ (FP < 0.05). M + SD (n = 3)
x
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/ 3.2 Tracheoscopic examinations <<
لم
Tracheoscopic images of the pig tracheal patchy in the dog. A; Slightly pale (similar to
mucosa erosion) pig tracheal patchy with suture material can be seen (arrow) at D28. B;
The protruding suture material is seen at D28 disappeared at D60. C; The area of the |
pig tracheal patchy looks normal (arrow) at 0 /
2
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3.3 Gene evaluation of the pig 16S and the dog
دعن عط متط عصممعطءهغلاء
3.4 Findings of histological examinations
D3 /cD20
Histological images of the graft at D90. A & B; Normal epithelium is seen on H&E and
Masson's trichrome stain. C; There are a few CD3+ cells (brown color) and no CD20+
cell (blue color) in the epithelium on immunohistochemistry 1
7
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jest that a small-sized (2 x 2 cm) wild-type pig tracheal patchy can be
ly engrafted into the trachea of the dog under immunosuppression, although
n of mucosa on the graft was seen at D30, in spite of xenotransplantation between
ie discordant species. It should need more potent immunosuppressive regimen to
control early graft rejection of the mucosa in pig to dog tracheal patchy model. Future
study will use a genetically modified pig as a donor in the context of a long-segment
tracheal defect model using in the dog xenotransplantation setting.
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1
پیت لیا
لان ا ثانا
_xenotransplantation?
وتا ال یلیام
ET ec
PCr i mel mtg
۱
۱
۱
1
ااانا عدداءع باامص0م
tell
Thousands of people are in dire need of a
transplant in the UK, but there just aren’t enough
donated organs to go round. So should we make up
the deficit with animal organs?
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imps J-Y, Roux FA, Sai” P, Gouin E,History of
nsplantation,Xenotransplantation 2005
.com/nature/xenotransplantation تم
[3]. Yung Puga Gisella L., Rieben Robert, Buhler Leo, Schuurman
Henk-Jan, Seebach Jorg D, Xenotransplantation: where do we stand in
2016?
[4]. Henk-Jan Schuurman,Léo Buhler, Theme issue on
Xenotransplantation in Asia,SchuBiomed Consultancy, Utrecht, The
Netherlands,University Hospitals, Geneva, Switzerland,2019
[5]. Tae-Ki Lee, Jong-Min Kim, Seok Hwa Choi, Pig tracheal patchy
xenotransplantation in the dog,2018
إل 2
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انالا