移植技术与研究

Background: There is little information in literature on renal allograft biopsy findings in renal allograft dysfunction in live related renal transplant recipients.

Material and Methods: A retrospective review of 1210 renal allograft biopsies from 575 renal transplant patients was carried out over a period of seven years from June 1997 till December 2004. The demographic, clinical, laboratory and biopsy findings were collected and analyzed.

Results: A total of 1210 graft biopsies were performed on 575 patients. The mean age of recipients and donors was 29.2±9.7 years, and 35.7±10.5 years, respectively. The males were predominant among recipients (76.7 vs. 23.3%), while among donors they only slightly outnumbered females (51.8 vs. 48.2%).

Regarding pathological lesions, acute rejection was seen in 292 (24%) cases, followed by acute tubular injury and cyclosporine A (CsA) toxicity, found in 281 (23.2%) and 134 (11%) cases respectively. Chronic allograft nephropathy (CAN) with variable degree of tubular atrophy was seen in 361 (29.8%) cases. Seventy nine cases (6.5%) of acute pyelonephritis were detected on graft biopsies. A number of rare lesions were also found, including 13 (1.07%) cases of recurrent/de novo renal disease, and 13 (1.07%) of polyoma virus infection. Five cases of CsA induced hemolytic uremic syndrome (HUS) were also noted.

Conclusion: In conclusion, the incidence of acute rejection is low in our patients as compared to cadaveric renal transplant recipients as reported in Western studies and CsA toxicity is more common. Recurrent/de novo renal disease is uncommon in our patients.

Mesenchymal stem cells are able to differentiate in various cell lineages and they have shown immunomodulatory properties in vitro, altering the cytokine secretion profile of T helper, T effector and dendritic cells and stimulating natural killer cells towards an anti-inflammatory and tolerant phenotype. In vivo they prolong skin allograft survival and may decrease graft-versus-host disease after hematopoietic stem cell transplants. In this work we studied the effects of mesenchymal stem cell treatment in an allogeneic heterotopic heart-lung transplant model.

The following experimental groups were formed: A) Control B) Immunosuppressive therapy (Cyclosporine A) C) Mesenchymal stem-cell intravenous infusion D) Mesenchymal stem-cell infusion plus immunosuppressive treatment.

The infusion of mesenchymal stem cells improved the mean graft survival up to 14.5±3.7 days with respect to the control group (3±0.6 days). Treatment with Cyclosporine A plus mesenchymal stem cells (group D) produced a mean survival time of 18.25±4.9 days, and was not significantly different to the results for group B (21.75±3.5 days). Furthermore, in the immunosuppressive treatment and the mesenchymal stem cell treatment, histological analysis revealed a reduction in the grade of rejection in heart and lung grafts. This decrease was most significant in group D.

In conclusion, mesenchymal stem cells alone or in combination with Cyclosporine A were able to prolong graft survival time. These data suggest that, in vivo, mesenchymal stem cells retain their ability, already shown in vitro, to suppress lymphocyte activation and proliferation.