The document provides guidelines and information on xenotransplantation. It discusses the concept of xenotransplantation, using animal organs or tissues for human transplantation to address organ shortages. The history of xenotransplantation is reviewed, noting early attempts dating back to the 1600s using animal bone and skin for human grafts. Guidelines from the Indian Council of Medical Research on experimental xenotransplantation are presented, focusing on oversight, long-term studies, and case-by-case approval. Recent research efforts led by George Church are also summarized, using CRISPR gene editing to modify pig embryos in an attempt to eliminate viruses and reduce immune response when transplanting pig organs into humans.

1. “GUIDELINES FOR
XENOTRANSPLANTATION”
Department of Bioengineering and Technology
Gauhati University Institute Of Science And Technology
Submitted By
Achyut Bora 130209003
Subject: Clinical Research Management

2. 2
CONTENTS
 CONCEPT
 HISTORY OF XENOTRANSPLANTATION
 IMPORTANCE OF XENOTRANSPLANTATION
 CHOOSING OF DONOR SPECIES
 XENOTRANSPLANTATION REJECTION
 GUIDELINES ON XENO-TRANSPLANTATION BY ICMR
 RECENT RESEARCH ON XENOTRANSPLANTATION

3. CONCEPT
Xenotransplantation refers to any procedure that involves the
transplantation, implantation, or infusion into a human recipient of
either
(a) live cells, tissues, or organs from a nonhuman animal source, or
(b) human body fluids, cells, tissues or organs that have had ex vivo
contact with live nonhuman animal cells, tissues or organs.
E.g:
 transplantation of xenogeneic hearts, kidneys, or pancreatic tissue
to treat organ failure,
 implantation of neural cells to ameliorate neurological degenerative
diseases,
 administration of human cells previously cultured ex vivo with live
nonhuman animal antigen-presenting.
It was formulated to overcome the shortage of donor organs.
3

4. 4
HISTORY OF XENOTRANSPLANTATION
 1682 – Bone from a dog was used in Russia in an attempt to repair his injured skull. This attempt was
reported successful, but the Russian had the bone removed soon after surgery under threat of the
church of excommunication.
 Late 1800’s – Frog Skins were often used as a way of healing burns or skin ulcers by grafting said skin
directly onto the patient’s skin. One British Army surgeon was known to have claimed using this
procedure a plethora of times with good results.
 1905 – French Surgeon grafts kidney tissues from a rabbit into a child, the child died two weeks later.
 1964 – A 68-year-old man dies two hours after receiving a Chimpanzee heart.
 1969-1974 – Chimpanzee livers were transplanted into three children. They only survived between
one to fourteen days.
 1977 – A 25-year-old woman receives a baboon heart but dies only six hours after surgery. About the
same time a 60-year-old man receives a chimpanzee heart to assist his own heart, but dies four days
after.

5. IMPORTANCE OF XENOTRANSPLANTATION
To overcome the shortage of organ for clinical implantation
in worldwide.
Cellular transplants could provide treatment for people with
diabetes, Alzheimer's or Parkinson's diseases.
Tissue xenotransplantation's could include skin grafts for
burn patients, corneal transplants for the visually impaired
or bone transplants for reconstructing limbs.
Organ xenotransplantation could include whole hearts,
lungs, livers, kidneys or pancreases.
Xenotransplantation also is and has been a valuable tool
used in research laboratories to study developmental
biology.
Patient derived tumor xenografts in animals can be used to
test treatments.
5

6. CHOOSING THE DONOR SPECIES
TYPE BETWEEN EXAMPLE
CONCORDANT Closely
related/simil
ar species
Baboon Human
DISCORDANT Distantly
related/
dissimilar
species
Pig Human
6

7. XENOTRANSPLANTATION
REJECTION;IMMUNOLOGICAL BARRIERS
3.Cellular Xenograft Rejection,
1.Hyperacute Xenograft Rejection, HXR
2.Acute vascular Xenograft Rejection,ACXR
4.Chronic Xenograft Rejection,
7

8. GUIDELINES ON XENO-TRANSPLANTATION BY ICMR
1. Experimental Xeno-transplantation must
only be permitted between different animal
species. Animal - to - man transplants must
not be permitted at the present level of
knowledge, which may be referred to the
Central/National Ethical Committee on
Human Research.
8

9. 2. Institutional scientific and ethics committees must approve
of such research studies, with special attention being paid to
their relevance, availability of facilities for extensive,
sophisticated and long-term studies for transmission of
disease through transplantation.
9

10. 3. An advisory committee consisting of reputed scientists in the field,
medical professionals, veterinary experts and microbiologists must
oversee all such transplants.
10

11. 4. Records on all research studies
must be detailed, scrupulously
maintained and kept available for a
long period of time, perhaps decades.
11

12. 5. Safeguarding the interest of the pioneer human recipients when such
transplants are permitted in future, it is proposed that each and every
animal - to – man transplant be very carefully vetted and sanctioned on a
case-by-case basis. In each instance, extensive studies on the animals to
ensure freedom from infection must be made mandatory. The human
recipients of tissues or organs must be carefully followed up over a long
term.
12

13. 6. Research involving the transplantation of human embryonic cells
(hESc), human embryonic germ cells (hEGc) or human somatic cells
(hSSc) of a pluripotent or multipotent nature into animals may be
done provided that:
i) The research is designed to reconstitute a specific tissue or organ
to derive a pre-clinical model.
13

14. 14
ii) There is evidence from prior studies that the
cells are not likely to contribute to gametes.

15. 15
RECENT RESEARCH ON XENOTRANSPLANTATION
 Pigs could be the perfect organ donar with gene editing
 George Church, a geneticist at Harvard Medical School and co-founder of the biotech
company eGenesis, hopes to change that; he had announced that he and his colleagues
had used the gene editing tool CRISPR to modify an unprecedented number of genes in
pig embryos in order to make them easier to transplant into humans.
 Church and his colleagues are combating two of the biggest reasons why pig organ
transplants haven’t worked in humans. First, transplants from pigs are more likely to
infect the human recipient with nasty viruses which are incorporated in its genetic code.
So the researchers have modified 62 of those genes in pig embryos—that’s more than ten
times the number of genes that have ever been edited in any other animal.
 The other issue is that recipients’ immune systems launch a substantial attack against
transplanted pig organs, requiring the patients to keep taking immunosuppressant drugs as
long as they have that transplanted organ in their bodies. Church’s team addressed that,
too, tweaking 20 genes that provide the blueprints for proteins found on the surface of pig
cells that trigger the immune response.

16. 16
 In order for their organs to be viable in humans, pig embryos would eventually
need both types of modifications. And though the researchers have not yet
combined them in one pig embryo, they will soon be ready to start implanting the
experimental embryos into mother pigs and raising the pigs that result. They plan to
develop a method to make the organs as inexpensive as possible.
George M. Church

17. 17