Transplant

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Transplant Immunology
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WHY TRANSPLANT TISSUES OR ORGANS? Replace
dysfunctional/nonfunctional tissue or
organs -------------------------------------------
----------------------------------- - High
technology medicine Specialized healthcare
professionals Specialized facilities
Specialized support Pathology Radiology -
Life saving - Very Expensive ---------------------
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-------
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DEFINITIONS OF TYPES OF TRANSPLANTS -------------
--------------------------------------------------
------- Classification scheme depends upon -
the species of donor and recipient - same or
different? - genetic similarity of donor
recipient (assuming both are form the same
species) - identical versus -
non-identical ------------------------------------
----------------------------------
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NOMENCLATURE Donor (graft) Recipient
(host) Same Genetically Type of Species
Identical transplant / tissue --------------
--------------------------------------------------
-------------- Self-gt Self Yes Yes Autologous
graft Autograft Twin A -gt B Yes Yes
Isogeneic graft (syngeneic) Isograft
(syngeneic graft) Person A --gt B Yes No
Allogeneic graft Allograft Species A
--gt B No No Xenogeneic graft
Xenograft ----------------------------------------
-------------------------------------- Also
applies to individuals of an inbred strain (e.g.,
inbred mice) Most common type of transplant in
humans
IMPORTANT!
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IMPORTANT!
WHAT ARE THE RULES OF TRANSPLANTATION? Type
of Graft Graft fate without immunosuppression
of the recipient (host) ----------------------
------------------------------------ Autograft A
ccepted Isograft Accepted Allograft Rejected
Xenograft Rejected -------------------------
--------------------------------- Graft (donor)
and Host (recipient) are antigenically
dissimilar
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Autograftt
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Twin A TWIN B
Tissue
Isograft (syngeneic graft)
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Tissue
Allogeneic graft (allograft)
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Tissue
Xenograft
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CLASSIFICATION BY GRAFT LOCATION
Orthograft transplanted organ is placed in the
normal organ location (heart) Heterotopic
transplanted organ is placed in an unnatural
location (kidney in pelvis)
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WHAT ARE THE TRANSPLANTATION ANTIGENS? Transplant
ation Relative Antigens Polymorphism --------
--------------------------------------------------
-------------------- 1) ABO Limited 2) Major
histocompatibility Very high complex (MHC) 3)
Minor histocompatibility Limited antigens(non-MHC
antigens) 4) Xenoantigens Extremely
high ---------------------------------------------
--------------------------------- Human MHC
HLA Complex, class I and class II MHC
IMPORTANT!
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IMPORTANT
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CONCEPT -----------------------------------------
------------------------------------- - the
greater the difference in peptide
sequences between graft and recipient -
the stronger the immune response to the graft
(donor) ------------------------------------------
------------------------------------
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HOW CAN FOREIGN CLASS II MHC PRESENT PEPTIDES TO
HOST TCRs?
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Classification of the phases of tissue rejection
Minutes- Hours Days Weeks
Months Years
Hyper- acute
Acute
Subacute
Chronic
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Pre-existing immunity to graft antigens
CMI Antibody CMI
Antibody CMI
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TIME TO TISSUE REJECTION IN MICE -----------------
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------- Skin graft in mice strain A --gt Immune
strain B response First set
rejection 11 - 15 days Primary Second set
rejection 6 - 8 days Secondary -----------------
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--------
IMPORTANT
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First Kidney Transplant Surgery 1950
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Transplantation

• From Kidney to Stem cell

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History of Transplantation in Iran
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• 1st kidney transplantation in 1967 in Shiraz
• Dr. Sanadi Zadeh

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1985

• 2 transplantation teams were organized and
  started to work actively
• 274 kidney transplant in 2 years

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L.R.D L.U.R.D. cadaveric
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1988

• L.U.R.D program organized and managed
  successfully
• Number of transplant teams grow to lt 20

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• To the end of 2002 gt 14888 kidney transplant
• Today gt 1500 kidney transplant/yr in Iran

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THE NUMBER OF RENAL TRANSPLANTS PERFORMED IN
IRAN FROM 1984 - 2002
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SOURCES OF KIDNEY DONATION IN IRAN 1984 -
2002
LURD 79 (N11 292)
LRD 19.2 (N2746)
CAD 1.8 (N250)
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PATIENT AND GRAFT SURVIVAL RATE IN LIVING
RELATED (LRD) AND LIVING UNRELATED (LURD) RENAL
TRANSPLANTATION In Hashemi Nejad Hospital ,
Tehran
Patient survival

Plt0.05
Graft survival
LRD (N469) LURD (N881)
Years Post Transplant
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GRAFT SURVIVAL RATES IN HLA IDENTICAL, ONE
HLA HAPLOTYPE MATCH AND LIVING UNRELATED
RENAL TRANSPLANT In Hashemi Nejad Hospital ,
Tehran
Plt0.001

P0.35
HLA Identical (n141) One HLA Haplo
(n307) Living Unrelated (n881)
Years Post Transplant
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Other Organ transplants

• Bone Marrow, Liver Heart

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1991

• 1ST BMT in Shariati Hospital (Dr. Ghavamzadeh et
  al

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1991-2006

• Total of 1468 BMT
• Allogenic 1044
• Autologous 324

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New Topics
Stem cell
Human Stem cell Repertoire
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What are stem cells?

• A stem cell is a cell whose job in the body is
  not yet determined
• Every single cell in the body stems from this
  type of cell
• Stem cells wait for signals to tell them what to
  become
• Until it receives a signal, it must wait
  patiently and divide slowly
• When it receives a signal, begin to differentiate
  
• The signals tell stem cell to turn on certain
  cell type it supposed to become

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• These Super cell have a magic clinical potential
  in tissue repair
• They represent the future relief of a wide range
  of incurable diseases
• They could replace defective organ and tissues
• They can restore the function of dysfunctional or
  non functional organs

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Where do they come from?
Embryonic Sc
Adult Sc
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• Early embryonic stages
• Some Fetal tissues
• The Umbilical Cord
• Several Adult organs
• Bone Marrow
• Peripheral blood
• Fat tissues
• Etc

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Adult stem cell?

• Every single organ has its own stem cell
• Bone Marrow
• Heamatopoietic stem cell (HSC)
• Endothelial stem cell (ESC)
• Mesenchymal stem cell (MSC)

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Mesenchymal Stem Cells (MSCs)

• MSCs are adult stem cells from BM that can
  differentiate into multiple nonhematopoietic cell
  lineages.
• They can differentiate into osteoblast,
  adipocytes, chondrocytes, myocytes,
  cardiomyocytes, astrocytes, oligodenrocytes and
  neurons.
• They have potential to down regulate and inhibit
  immune response in both recognition and
  elimination phases

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• Possible clinical application proposed for MSC
  include
• stem cell transplantation
• Stem cell strategies for the repair of damaged
  organ and gene therapy
• MSCs due to their immunomodulatory potential
  theoretically, they can be used allogenically

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The role of Mesenchymal Stem Cells in
relationship with injured somatic tissue and
non-immune cells
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CAN STEM CELLS BE ISOLATED AND USED?

• If so under what conditions and restrictions?

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• The low frequency of MSC in bone marrow
• necessitate the in vitro expansion prior to
• clinical use
• We evaluated the effect of long term culture on
  the senescence of these cells
• Surprisingly , MSC loses their characteristic
  after several passages
• Therefore
• It is much better to consider them for therapy
  early on

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BM MSC culture (passage 6)
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The goal of our stem cell therapy studies

• Assessing the safeness of the stem cell injection
• The patients improvement from a clinical point of
  view
• The degree of damaged tissue repair

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Mesenchymal Stem Cell therapy for Multiple
Sclerosis and Heart Diseases
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Results of MS treatment

• 10 MS patients with secondary progressive disease
  has been transplanted
• One patient improved 2.5 score in EDSS (expanded
  disability status scale)
• 4 others showed some degree of improvement
• 5 patients after MSCT has not hastened disease
  progress

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Results of MSCT in Heart disease

• Cardiac functional parameters of mean 18 month
  fallow up in test group
• Parameters Base line SD
  After MSC SD P value
• NYHA 2.75 0.70 1.38 0.51
  .000
• LVEF 38.75 13 48.75 6.4
  .005
• SPECT 11 2 7.75 1.1
  .002
• Cardiac functional parameters of mean 18 month
  fallow up in control group
• Parameters Base line SD
  After pro. SD P value
• NYHA 2.75 0.70
  2.13 0.35 .049
• LVEF 41.88 8.42
  42.50 8.86 NS
• SPECT 10.88 1.95 9.75
  1.58 .007

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Comparison of cardiac function in two groups.

• Groups NYHA LVEF
  SPECT
• before after
  before after before
  after
• Test group 2.75 1.38
  38.75 48.75 11
  7.75
• Control group 2.75 2.13
  41.88 42.50 10.88 9.75
• P value NS .005
  NS NS NS
  .013

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Potential Tumorigenicity of these cells
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Finally

• It seems, like all other issues,
• We must first consider all potential results and
  possibilities
• BEFORE ANY INTERVENTION
• Because
• NOTHING COMES TO US WITHOUT A DEGREE OF RISK