Xenotransplantation-the current status and prospects

Abstract

Introduction: There is a continuing worldwide shortage of organs from deceased human donors for transplantation into patients with end-stage organ failure. Genetically engineered pigs could resolve this problem, and could also provide tissues and cells for the treatment of conditions such as diabetes, Parkinson's disease and corneal blindness.

Sources of data: The current literature has been reviewed.

Areas of agreement: The pathobiologic barriers are now largely defined. Research progress has advanced through the increasing availability of genetically engineered pigs and novel immunosuppressive agents. Life-supporting pig kidneys and islets have functioned for months or years in nonhuman primates.

Areas of controversy: The potential risk of transfer of a pig infectious microorganism to the recipient continues to be debated.

Growing points: Increased attention is being paid to selection of patients for initial clinical trials.

Areas timely for developing research: Most of the advances required to justify a clinical trial have now been met.

Fig. 1

Human IgM and IgG antibody binding to wild-type (WT), GTKO/hCD46, and GTKO/hCD46/NeuGc-KO pig and human AECs by flow cytometry. Binding to GTKO/hCD46/NeuGc-KO pig cells is almost as low as to human AECs.

Fig. 2

(A) Blood glucose and pig C-peptide levels in a streptozotocin-induced diabetic cynomolgus monkey before and after intraportal transplantation of islets from a pig expressing the human complement-regulatory protein, CD46. No exogenous insulin was administered after the transplant. The normoglycemic monkey was electively euthanized after 12 months. Tx = day of islet transplantation. (B) Insulin immunostaining (in red) of a liver section in a monkey recipient of islets from a pig transgenic for human CD46, showing a healthy pig islet 12 months after transplantation (magnification ×200).