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Biomedical subjects

C Ricordi

Publications and source records attributed to C Ricordi.

At least 19 recordsLinked to original sources
PubMed1992

Systemic chimerism in human female recipients of male livers.

We have previously reported data from clinical and laboratory animal observations which suggest that organ tolerance after transplantation depends on a state of balanced lymphodendritic cell chimerism between the host and donor graft. We have sought further evidence to support this hypothesis by investigating HLA-mismatched liver allograft recipients. 9 of 9 female recipients of livers from male donors had chimerism in their allografts and extrahepatic tissues, according to in-situ hybridisation and molecular techniques 10 to 19 years posttransplantation. In 8 women with good graft function, evidence of the Y chromosome was found in the blood (6/8), skin (8/8), and lymph nodes (7/8). A ninth patient whose transplant failed after 12 years from recurrent chronic viral hepatitis had chimerism in her lymph nodes, skin, jejunum, and aorta at the time of retransplantation. Although cell migration is thought to take place after all types of transplantation, the large population of migratory cells in, and the extent of their seeding from, hepatic grafts may explain the privileged tolerogenicity of the liver compared with other organs.

ABO Blood-Group System↗
PubMed1992

Composition of human islet cell preparations for transplantation.

To study the cellular composition of human islet cell isolates for transplantation, formalin-fixed and paraffin-embedded cell pellets were stained by the immunoperoxidase method with a panel of antibodies characterising endocrine, epithelial, soft tissue and haematolymphoid components. Immediately after separation, the isolates contained 30-80% islet cells, differing mainly in the content of islet and acinar cells, whereas the soft tissue, ductal/ductular and haematolymphoid elements comprised a relatively constant 10-20%. After 1 week in culture the islet cell content of less highly purified isolates (30-40% islets) dropped dramatically to 5%. The highly purified isolates (70-80% islets) showed only a minimal change in cellular composition; however, approximately two-thirds of islet cells were degranulated and did not stain for insulin. Haematolymphoid components were still present in all cultured isolates. We conclude that primarily mechanical purification methods and short-term culture are not sufficient to eliminate highly immunogenic cells. In addition, short-term culture is deleterious to the isolate if a significant number of acinar cells is still present after enrichment.

Adult↗
PubMed1992

Effect of FK506 on insulin secretion in normal dogs.

In this report, we describe the effect of FK506 on glucose-mediated insulin release in normal dogs. Dogs were placed into one of two groups, group 1 dogs received FK506 (1 mg/kg/d orally) for 2 weeks, and group 2 dogs received FK506 at the same dose, but for 4 weeks. Following the treatment period, both groups of dogs were allowed a recovery period during which time no FK506 was administered. Intravenous glucose tolerance tests (IVGTT) were performed (0.5 mg/kg IV) before FK506 treatment, after 2 or 4 weeks of treatment, and following the recovery periods. Complete blood cell counts (CBC) and serum chemistries were also obtained at these times. Following FK506 treatment for either 2 or 4 weeks, the dogs experienced a delay in glucose disappearance in response to IV glucose injection. Insulin secretion during IVGTT was unchanged in dogs treated for only 2 weeks, but was significantly decreased in dogs treated for 4 weeks. Following the recovery period, glucose disappearance during IVGTT returned to normal in dogs that were treated for 2 weeks, and was more rapid than normal in dogs that had been treated for 4 weeks. Insulin secretion after the recovery period remained unchanged in group 1 dogs, but continued to be significantly reduced in group 2 dogs that had received FK506 for 4 weeks. No significant change was detected in the CBCs or serum chemistries.

Animals↗
PubMed1992

Detection of intrahepatic human islets following combined liver-islet allotransplantation.

This article describes the localization of intact insulin-containing intrahepatic islets after combined liver-islet allotransplantation. The patient was a 36-year-old woman who underwent upper abdominal exenteration for neuroendocrine carcinoma; 289,000 islets were transplanted via portal vein infusion immediately after complete revascularization of the liver. Immunosuppression was with low-dose FK-506. OKT3 and steroids were used to treat one rejection episode 2 weeks after transplantation, but the patient subsequently developed multiple infections and died 109 days after transplantation. At autopsy, the transplanted liver did not show any sign of rejection and well-preserved islets were present in portal triads sampled from the anterior inferior edge of the right lobe. Immunohistochemical labeling confirmed the presence of insulin-containing cells. This finding indicated that human islets can survive after intrahepatic allotransplantation, despite positive cross-match with no HLA antigen match, suggesting that upper abdominal exenteration and liver transplantation may constitute a protective factor for the survival of allogeneic human islets.

Adult↗
PubMed1992

Long-term survival of donor-specific pancreatic islet xenografts in fully xenogeneic chimeras (WF rat----B10 mouse).

We recently reported that reconstitution of lethally irradiated B10 mouse recipients with 40 x 10(6) untreated WF rat bone marrow cells resulted in stable fully xenogeneic chimerism (WF rat----B10 mouse). In these animals, the tolerance induced for skin xenografts was highly MHC specific in that donor-specific WF rat skin grafts were significantly prolonged while MHC-disparate third-party xenografts were rapidly rejected (median survival time [MST] = 9 days). We have now examined whether islet cell xenografts placed under the renal capsule of chimeras rendered diabetic with streptozotocin would be accepted and remain functional to maintain euglycemia. Animals were prepared, typed for chimerism at 6 weeks, and diabetes induced with streptozotocin. Donor-specific WF (Rt1Au) islet cell xenografts were significantly prolonged (MST greater than 180 days) in WF----B10 chimeras, while MHC-disparate third-party F344 rat (Rt1A1) grafts were rejected with a time course similar to unmanipulated B10 mice (MST = 8 days). The transplanted donor-specific islet cells were functional to maintain euglycemia, since removal of the grafts at from 100 to 180 days in selected individual chimeras uniformly resulted in return of the diabetic state. These data suggest that donor-specific islet cell xenografts are accepted and remain functional in mice rendered tolerant to rat xenoantigens following bone marrow transplantation.

Animals↗
PubMed1992

Human islet isolation and allotransplantation in 22 consecutive cases.

This report provides our initial experience in islet isolation and intrahepatic allotransplantation in 21 patients. In group 1, 10 patients underwent combined liver-islet allotransplantation following upper-abdominal exenteration for cancer. In group 2, 4 patients received a combined liver-islet allograft for cirrhosis and diabetes. One patients had plasma C-peptide greater than 3 pM and was therefore excluded from analysis. In group 3, 7 patients received 8 combined cadaveric kidney-islet grafts (one retransplant) for end-stage renal disease secondary to type 1 diabetes mellitus. The islets were separated by a modification of the automated method for human islet isolation and the preparation were infused into the portal vein. Immunosuppression was with FK506 (group 1) plus steroids (groups 2 and 3). Six patients in group 1 did not require insulin treatment for 5 to greater than 16 months. In groups 2 and 3 none of the patients became insulin-independent, although decreased insulin requirement and stabilization of diabetes were observed. Our results indicate that rejection is still a major factor limiting the clinical application of islet transplantation in patients with type 1 diabetes mellitus, although other factors such as steroid treatment may contribute to deteriorate islet engraftment and/or function.

Adolescent↗