“GUIDELINES FOR

XENOTRANSPLANTATION”

Department of Bioengineering and Technology

Gauhati University Institute Of Science And Technology

Submitted By

Achyut Bora 130209003

Subject: Clinical Research Management

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CONTENTS

CONCEPT HISTORY OF XENOTRANSPLANTATION

IMPORTANCE OF XENOTRANSPLANTATION

CHOOSING OF DONOR SPECIES XENOTRANSPLANTATION REJECTION

GUIDELINES ON XENO-TRANSPLANTATION BY ICMR

RECENT RESEARCH ON XENOTRANSPLANTATION

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.

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4HISTORY 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.

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.

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CHOOSING THE DONOR SPECIES

TYPE BETWEEN EXAMPLE

CONCORDANT Closely related/similar species

Baboon Human

DISCORDANT Distantlyrelated/dissimilarspecies

Pig Human

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XENOTRANSPLANTATION

REJECTION;IMMUNOLOGICAL BARRIERS

3.Cellular Xenograft Rejection,

1.Hyperacute Xenograft Rejection, HXR

2.Acute vascular Xenograft Rejection,ACXR

4.Chronic Xenograft Rejection,

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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.

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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.

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3. An advisory committee consisting of reputed scientists in the field,

medical professionals, veterinary experts and microbiologists must

oversee all such transplants.

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4. Records on all research studies

must be detailed, scrupulously

maintained and kept available for a

long period of time, perhaps decades.

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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.

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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.

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

15RECENT 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 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

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