DIFFERENT TYPES OF XENOTRANSPLANTS: WEIGHING THE RISK

 

It is also necessary to establish differences in the degrees of risk associated with different types of xenotransplants. Generally, the more vascularized the tissue, the greater the risk associated with its transplantation. This stems from both increased chances of immunological complications, as well as the decreased range of alternative treatments as vascularization increases.

	Safest End of Xenotransplantation Spectrum	Midrange of Xenotransplantation Spectrum	Riskiest End of Xenotransplantation Spectrum
Disease Treated	Diabetes	Kidney Failure	Heart Failure
Organ Transplanted	Pancreatic Islets	Kidney	Heart
Donor Animal	Specific-pathogen-free (SPF) pig	SPF transgenic pig	Baboon
Immunosuppression	None	Systemic (Lifelong)	Systemic (Lifelong)
Graft Failure	Return to insulin injections	Dialysis	Death

Source: The Islet Foundation

 

The differences in viability/appicability between vascularized and non-vascularized tissue is furthered illustrated in the following table:

	Islet Xenotransplantation	Whole Organ Xenotransplantation
Donor Animal	SPF pigs only. Transgenic pigs are not required.	Both transgenic SPF pigs (lowest risk of zoonotic infection) and non-human primates (higher zoonotic infection risk), depending on organ.
Immunosuppression	No immunosuppression - Immunobarriers protect transplanted tissue. Risk of infection from all sources is minimized, and adverse effects such as cancer are precluded.	Systemic immunosuppression - Higher risk of infection and adverse effects. Immunosuppression is cited as a major risk factor associated with xenografts.
Hyperacute Rejection	None - Since islets do not contain endothelial cells, hyperacute rejection typical of non-human organs does not occur.	Strong - Because of endothelial cells and species mismatch, whole organs will experience immediate hyperacute rejection, unless the recipient is sufficiently immunosuppressed.
Acute Vascular Rejection	None - Since islets are free tissue not connected directly to the recipient's vascular system, acute vascular rejection is avoided.	Strong - Organs such as hearts, liver, or kidney must be connected to recipient's vascular system, resulting in immediate destruction of the blood vessels unless the recipient is sufficiently immunosuppressed.
Physiologic Differences	Minimal - Normal blood glucose range is 70-100 mg/dl for humans, 70-105 mg/dl for pigs. Pig islets would maintain a normal blood glucose setpoint in humans. Organ matching is not an issue, as it is impossible to transplant too many islets.	Variable - Pigs and humans differ significantly in most physiological parameters. It is not known if these differences will lead to problems in liver, heart, kidney, or other whole organ xenografts.
Historical Efficacy	Compelling - Pig insulin has been used for 77 years to control blood glucose in people with diabetes.	None - There is no track record comparable to pig insulin for any animal whole organ.
Consequence of Failure	Minimal - The recipient will revert to normal injected insulin therapy.	Severe - Failure of a whole organ may result in death or serious illness.
Retransplantation	Minor - Injection or simple surgery to add additional islets, or to remove islets for examination.	Major - Intrusive and risky surgery to retransplant in event that recipient survives graft failure.

Source: The Islet Foundation