1. Prolonged Survival of Porcine Hepatocytes in Cynomolgus Monkeys
Hideo Nagata, Ryuta Nishitai, Chiyoe Shirota, Jia-Lin Zhang, Cody A. Koch, Jin Cai, Michel Awwad, Henk-Jan Schuurman, Uwe Christians, Michio Abe, Janina Baranowska–Kortylewicz, Jeffrey L. Platt, Ira J. Fox 
Gastroenterology 
Volume 132, Issue 1, Pages (January 2007)
DOI: /j.gastro
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2. Figure 1
Porcine albumin levels in the peripheral blood of monkeys following intrasplenic transplantation of porcine hepatocytes. Three monkeys with normal hepatic function underwent intrasplenic transplantation with 1 to 2 billion porcine hepatocytes. Recipient monkeys were treated with Thymoglobulin, methylprednisolone, and anti-CD25 at the time of transplantation and were maintained on cyclosporine A, FTY720, RAD, and methylprednisolone thereafter. After transplantation, the concentration of porcine albumin in the peripheral blood was used as a measure of pig hepatocyte engraftment. The transplanted porcine hepatocytes functioned from 25 days to over 80 days following a single infusion of cells. The first recipient died on the 25th postoperative day from disseminated cytomegalovirus (CMV) infection with a functioning graft. The 2 subsequent recipients were treated with less immune suppression and with Gancyclovir and developed no complications from CMV, nor did they develop any other ill effects from the transplant procedure or immune suppression.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2007 AGA Institute Terms and Conditions

3. Figure 2
Porcine albumin levels in the peripheral blood of immune-deficient mice following transplantation of porcine hepatocytes. In order to retrospectively assess the capacity of porcine hepatocytes from cell preparations to engraft normally, 1 million cells were suspended in 50 μL of RPMI and transplanted into the spleens of 8-week-old male SCID mice. Porcine serum albumin levels in mice were measured for 2 weeks after transplantation. Porcine albumin levels increased appropriately following transplantation in immune-deficient mice, which do not reject xenogeneic hepatocytes. The porcine albumin level decreases in a manner similar to that seen in the immune-suppressed primate recipients of porcine hepatocytes.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2007 AGA Institute Terms and Conditions

4. Figure 3
Imaging of engrafted pig hepatocytes in the spleen. Monkeys with normal hepatic function underwent intrasplenic transplantation with 1 to 2 billion porcine hepatocytes. Hepatocytes were suspended in alginate prior to transplantation to create a matrix that would enhance engraftment in the spleen and then infused directly into the spleen by splenic puncture. After transplantation, the concentration of porcine albumin in the peripheral blood, as a measure of pig hepatocyte engraftment, increased. As a further test for the engraftment and function of the hepatocyte grafts, asialoglycoprotein receptor scintigraphy was performed in 1 monkey. One mCi of AF-(99mTc-SHNH)6 was injected into the central venous catheter line of the anesthetized monkey, and whole body imaging was performed with a planar gamma camera. (A) Prior to transplantation, nuclear scanning demonstrates uptake only in the liver, representing uptake by native hepatocytes and pooling of labeled AF in the heart. (B) After porcine hepatocyte infusion, nuclear scanning again demonstrates radionuclide uptake in the liver and heart but also demonstrates uptake in the area of the spleen, confirming porcine hepatocyte engraftment in the spleen 40 days after transplantation.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2007 AGA Institute Terms and Conditions

5. Figure 4
Porcine albumin levels in the peripheral blood of a monkey following intrasplenic retransplantation of porcine hepatocytes. Monkey 41–495 underwent intrasplenic transplantation with 1 billion porcine hepatocytes. After the level of porcine albumin in the serum of this recipient decreased to 0.1 mg/dL, hepatocytes isolated from 2 other outbred pigs were transplanted. One retransplant, conducted 84 days after the first transplant, generated a minimal increase in the level of swine albumin in the serum. This transplant was associated with a minimal increase in the level of porcine albumin in the peripheral blood of immune-deficient mice transplanted with an aliquot of these porcine hepatocytes. The other retransplant, performed on day 111, however, functioned for 142 additional days (ie, to day 253 after the original transplant). This animal died with a functioning graft from complications associated with replacement of a central venous catheter.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2007 AGA Institute Terms and Conditions

6. Figure 5
Immune response to porcine hepatocytes following transplantation in monkeys. To examine the immune response to xenotransplantation of hepatocytes, levels of antibodies in the monkeys specific for Galα1-3Gal were measured. IgG and IgM anti-Gal antibody serum levels were determined by ELISA using microtiter plates coated with αGal trisaccharide type II (Galα1,3Galβ1,4GlcNAc) or type VI (Galα1,3Galβ1,4Glc). Before transplantation, levels of antibodies specific for Galα1-3Gal (both IgG and IgM isotypes) were low in 1 animal (A) (41–508), in the range of normal values in another animal (B) (41–155), and high in the third animal (C) (41–495). After transplantation, the level of anti-Galα1-3Gal antibodies increased slightly in 1 recipient. This increase, however, is within the range of normal variation. The level of anti-Galα1-3Gal antibodies remained without significant change in the other 2 recipients. Additional studies also showed that no IgM or IgG antibodies were generated to epitopes that might be on pig hepatocytes other than Galα1-3Gal. Although the lack of significant change in serum antibody levels may reflect binding of antibodies to the grafts, the results suggest that xenotransplantation of hepatocytes evoked a less intense humoral immune response than seen after organ transplantation.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2007 AGA Institute Terms and Conditions