Transplantation In Subjects Research Articles

Disentangle beneficial effects of strain engraftment after fecal microbiota transplantation in subjects with MetSyn

ABSTRACT Fecal Microbiota Transplantation (FMT) has emerged as a potential modality for mitigating microbiome-associated diseases. Despite this potential, the precise causal pathways by which specific gut microbiota strains induce remission remain inadequately elucidated. In this study, we aimed to discern the impact of engraftment of donor-infused strains on alterations in plasma metabolites, subsequently contributing to the amelioration of clinical parameters involved in subjects with metabolic syndrome (MetSyn) receiving an FMT. We observed that a higher fraction of donor strains engrafted in the recipient is correlated to a reduction in diastolic blood pressure and found specific strain associations through canonical correlation analysis. Integrating the metabolomics profile shows that engraftment of Collinsella aerofaciens and Fusocatenibacter saccharovorans was related to a reduction in 2-oxoarginine in plasma, which was subsequently correlated to a reduction in diastolic blood pressure. In conclusion, we applied a novel framework to elucidate on the complex and heterogenous FMT intervention, establishing a connection between engrafted microbiota and clinical outcome parameters. Our findings underscore the potential therapeutic efficacy of FMT in ameliorating MetSyn, demonstrating a potential contribution of microbial strain engraftment to the improvement of MetSyn via modulation of circulating metabolites.

Gut bacteriophage dynamics during fecal microbial transplantation in subjects with metabolic syndrome

ABSTRACT Metabolic Syndrome (MetS) is a growing public health concern worldwide. Individuals with MetS have an increased risk for cardiovascular (CV) disease and type 2 diabetes (T2D). These diseases – in part preventable with the treatment of MetS – increase the chances of premature death and pose a great economic burden to health systems. A healthy gut microbiota is associated with a reduction in MetS, T2D, and CV disease. Treatment of MetS with fecal microbiota transplantation (FMT) can be effective, however, its success rate is intermediate and difficult to predict. Because bacteriophages significantly affect the microbiota membership and function, the aim of this pilot study was to explore the dynamics of the gut bacteriophage community after FMT in MetS subjects. We performed a longitudinal study of stool bacteriophages from healthy donors and MetS subjects before and after FMT treatment. Subjects were assigned to either a control group (self-stool transplant, n = 3) or a treatment group (healthy-donor-stool transplant; n-recipients = 6, n-donors = 5). Stool samples were collected over an 18-week period and bacteriophage-like particles were purified and sequenced. We found that FMT from healthy donors significantly alters the gut bacteriophage community. Subjects with better clinical outcome clustered closer to the heathy donor group, suggesting that throughout the treatment, their bacteriophage community was more similar to healthy donors. Finally, we identified bacteriophage groups that could explain these differences and we examined their prevalence in individuals from a larger cohort of MetS FMT trial. Trial information- http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2705; NTR 2705

Effects of fecal microbiota transplantation in subjects with irritable bowel syndrome are mirrored by changes in gut microbiome

ABSTRACT Irritable bowel syndrome (IBS) is a common disorder of the lower gastrointestinal tract. The pathophysiology is far from settled, but a gut microbial dysbiosis is hypothesized to be a contributing factor. We earlier published a randomized double-blind placebo-controlled clinical trial on fecal microbiota transplantation (FMT) for IBS – the REFIT trial. The present data set describes the engraftment and includes participants from the study who received active FMT; 14 participants with effect of FMT (Effect) and 8 without (No effect). Samples were collected at baseline, after 6 and 12 months. Samples from the transplants (Donor) served as a comparator. In total 66 recipient samples and 17 donor samples were subjected to deep metagenomic sequencing, and taxonomic and functional analyses were performed. Alpha diversity measures showed a significantly increased diversity and evenness in the IBS groups compared to the donors. Taxonomic profiles showed higher relative abundance of phylum Firmicutes, and lower relative abundance of phylum Bacteroidetes, compared to donors at baseline. This profile was shifted toward the donor profile following FMT. Imputed growth rates showed that the resulting growth pattern was a conglomerate of donor and recipient activity. Thirty-four functional subclasses showed distinct differences between baseline samples and donors, most of which were shifted toward a donor-like profile after FMT. All of these changes were less pronounced in the No effect group. We conclude that FMT induces long-term changes in gut microbiota, and these changes mirror the clinical effect of the treatment. The study was registered in ClinicalTrials.gov (NCT02154867).

1982-P: Laparoscopic Sleeve Gastrectomy as Bridge to Kidney Transplantation: Pilot Study in Subjects with Renal Failure and Obesity

Obesity and associated metabolic complications are established risk factors for the development and progression of chronic kidney disease; however, BMI (body mass index)>35 kg/m2 is a contraindication for kidney transplantation. The aim of our study was to reduce excess body weight via laparoscopic sleeve gastrectomy (LSG) in obese patients with end-stage renal disease (ESRD) in order for them to become eligible for the transplantation program. Subjects with ESRD undergoing hemodialysis or peritoneal dialysis and BMI>35kg/m2 without serious comorbidities were included into the study. Anthropometric and biochemical parameters were measured before and 1, 3 and 6 months after LSG. In the thus far enrolled 7 subjects (6 females, aged 47.6 ± 9.6 years) LSG resulted in improved body weight (118.0 ± 17.6 vs. 107.5 ± 14.5 vs. 105.5 ± 14.4 vs. 99.5 ± 10.7 kg for baseline vs. 1 vs. 3 vs. 6 months, p<0.001) and BMI (42.5 ± 3.8 vs. 38.6 ± 3.2 vs. 37.4 ± 2.8 vs. 37.0 ± 3.1 kg/m2 for baseline vs. 1 vs. 3 vs. 6 months, p<0.001) with 3 subjects achieving target BMI<35 kg/m2 1-6 months after LSG enabling their inclusion in the kidney transplantation waiting list. Weight loss was accompanied by significant decrease of systolic (160.0 ± 25.0 vs. 128.7 ± 31.2 mmHg, p=0.042) and diastolic (99.0 ± 13.6 vs. 75.5 ± 12.0 mmHg, p=0.022) blood pressure with antihypertensive medication being reduced in 2 subjects. The only subjects with diabetes mellitus (type 1) showed improvement in fasting glucose (15.8 vs. 9.3 mmol/l) and HbA1c (84 vs. 68 mmol/mol) and a 25% reduction of prandial insulin dose 1 month after LSG. No peri- or postoperative complications have been observed to date. To conclude, our pilot data suggest LSG to be an efficient and safe method to achieve the necessary weight reduction enabling renal transplantation in subjects with renal failure and higher degrees of obesity. Disclosure V. Hrádková: None. M. Kasalicky: None. S. Rajnochova-Bloudickova: None. I. Lankova: None. H. Kratochvilova: None. M. Mraz: None. K. Dvorakova: None. S. Slaba: None. J. Mendl: None. O. Viklicky: None. J. Fronek: None. M. Haluzik: Advisory Panel; Self; Lilly Diabetes, Sanofi. Consultant; Self; Ethicon US, LLC. Speaker’s Bureau; Self; AstraZeneca, Mundipharma International, Novartis AG, Novo Nordisk A/S. Funding Institute for Clinical and Experimental Medicine (00023001)

206-LB: Survival after Islet Transplantation in Subjects with Type 1 Diabetes: 20-Year Follow-Up

Type 1 diabetes (T1D) is associated with premature mortality due to T1D-related acute and chronic complications, including severe hypoglycemic events (SHE), cardiovascular (CVD) and renal disease. Islet transplantation (ITx) has been shown to provide near-normal glycemic control and protection from SHEs in a select group of patients with T1D. We retrospectively evaluated the survival of ITx recipients (n= 49) followed up to 20 years. Subjects were transplanted and followed from 2000-2020 at our institution. Study cohort included 29 females (59.2%). Median age at T1D diagnosis was 13.2 (6.7 - 20.0) years while mean age and median duration of T1D at ITx was 42.8 ± 8.3 years and 29.5 (17.2 - 38.2) years, respectively. Two subjects (4.08%) died during follow-up. Duration of graft function was 4.4 (1.3 - 12.2) years. Cumulative survival post-ITx was 100%, 96% and 85%, at 10, 15 and 20 years follow-up, respectively. Results suggest that despite chronic immunosuppression, near-normal metabolic control achieved following ITx can reduce the increased mortality risk associated with T1D. Possible factors accounting for these results include lower cumulative hyperglycemic exposure and prevention of SHE. Subjects selected for ITx represent a highly vulnerable group at risk of recurrent SHE and death. ITx may prevent mortality by preventing SHE and reducing CVD risk factors in selected patients with T1D. Disclosure C. Ricordi: None. J. Lemos: None. D. Baidal: None. A.M. Alvarez: None. R. Alejandro: None. Funding Diabetes Research Institute Foundation; State of Florida; JDRF; The Leona M. and Harry B. Helmsley Charitable Trust; University of Miami Clinical and Translational Science Institute

Fecal calprotectin and fecal indole predict outcome of fecal microbiota transplantation in subjects with recurrent Clostridium difficile infection

Fecal calprotectin and indole were studied in 134 subjects with recurrent CDI before and after FMT. Reduced fecal calprotectin (p = 0.0353, 95% CI 0.1305–0.1439) and rising levels of indole (p < 0.0001, 95% CI < 0.0001–0.0003) predicted successful treatment. A ratio of recal calprotectin/indole may provide prognostic value for FMT (p = 0.0004, 95% CI 0.22–0.87).

Alteration of the Microbial Community of the Gut in Response to Fecal Microbiota Transplantation In Subjects With Clostridium difficile Infection

Alteration of the Microbial Community of the Gut in Response to Fecal Microbiota Transplantation In Subjects With Clostridium difficile Infection

Lung Transplantation as Rescue Therapy in Patients Too Sick to Be Discharged From Acute Care

BackgroundThere is an increasing demand for lung transplantation in patients in advanced respiratory failure. Although many of these patients do not require mechanical ventilation or extracorporeal membrane oxygenation, an increasing number are critically ill. In this single-center study, we have analyzed our experience with lung transplantation in subjects who were inpatients at the time of their transplant and not expected to survive to discharge. MethodsBetween July 2006 and March 2012, we performed 274 bilateral sequential lung transplants and 34 single-lung transplants. Twenty-six patients who were inpatients at the time of their transplant, and were not expected to survive to hospital discharge, formed the inpatient group in this retrospective review. The remaining 281 outpatient lung transplant patients formed the comparison group. ResultsThe inpatient group spent significantly fewer days on the waiting list compared to the outpatient group. Postoperative survival was significantly poorer in the inpatient group compared to the outpatient group (P = .001), and this was most noticeable in the first 90 days. There was no significant difference in survival between the inpatient transplant cohort and a historically comparable wait list cohort (P = .614). ConclusionLung transplantation in critically ill inpatients, although associated with a survival advantage compared to not transplanting them, does give poorer survival results compared to postoperative survival in outpatient patients.

S19 * LIVER TRANSPLANTATION IN PATIENTS WITH ALCOHOLIC LIVER DISEASE

S19 * LIVER TRANSPLANTATION IN PATIENTS WITH ALCOHOLIC LIVER DISEASE

Systemic arterial hypertension in children following renal transplantation: prevalence and risk factors

Control of blood pressure (BP) following renal transplantation may improve allograft and patient survival. Our aims were (i) to describe the distribution of BP and the prevalence of systolic and/or diastolic hypertension in children over the first 5 years following renal transplantation and (ii) to evaluate clinical risk factors and centre-specific factors associated with hypertension in this population. We conducted a retrospective case note review of all current paediatric kidney transplant patients in the UK, with data collected at 6 months, 1, 2 and 5 years following transplantation in subjects with hypertension (systolic and/or diastolic BP > 95th > ) and non-hypertensive subjects BP ≤ 95th > . In total, 27.3% (117/428), 27.6% (118/428), 26.0% (95/365) and 25.6% (50/195) of the patients were hypertensive (systolic and/or diastolic BP > 95th > ) at 6 months, 1, 2 and 5 years following transplantation, respectively. A total of 58.4% of the patients at 6 months, 52.8% at 1 year, 48.2% at 2 years and 48.2% at 5 years were receiving anti-hypertensive therapy, of whom 31.6-36.6% remained hypertensive. When subjects were identified as being hypertensive, on anti-hypertensive medication or had untreated hypertension (systolic and/or diastolic BP > 95th > ), 66.4, 61.0, 56.4 and 55.9% of patients were hypertensive at 6 months, 1, 2 and 5 years, respectively. In a multivariate model, odds ratios for systolic hypertension were 4.16 (deceased versus living donor), 2.65 (lowest versus highest quartile of height z-score) and 2.07 (if on anti-hypertensive; yes versus no). There was significant variation in prevalent rates of hypertension between centres (P < 0.0001) that remained significant (P = 0.003) after adjustment for all the factors in the multivariate model. Control of BP after kidney transplantation remains sub-optimal in paediatric centres in the UK. Just over 25% of patients remain hypertensive 5 years following transplantation. Significant differences between centres remain unexplained and may reflect differences in assessment and management of hypertension.

Recurrence of autoreactive antigen-specific CD4+ T cells in autoimmune diabetes after pancreas transplantation

CD4+ T cells specific for the diabetes-associated autoantigen GAD65 were analyzed using peripheral blood samples after pancreas transplantation in subjects with T1D with clinical evidence of recurrent autoimmune diabetes. MHC class II tetramers facilitated the identification and cloning of antigen-specific autoreactive cells, which were found at several time points over a multiyear span, in spite of chronic immunosuppression of the subjects. Comparisons of TCR clonotypes by cDNA sequencing revealed that identical T cells were present in the circulation, separated by long time intervals, consistent with a persistent memory response associated with recurrent autoimmunity.

Long-term tolerance to allogeneic thymus transplants in complete DiGeorge anomaly

Thymus transplantation in subjects with complete DiGeorge anomaly using postnatal allogeneic HLA-nonmatched cultured thymus tissue provides immunoreconstitution. Tolerance of the newly developed T cells toward the donor thymus has not previously been studied. Mixed lymphocyte cultures were used to test 12 thymus transplant recipients for long-term tolerance toward their thymus allografts. Two subjects tested for responses toward thymus donor peripheral blood mononuclear cells showed significantly less reactivity toward the donors compared to responses against third-party allogeneic cells. Peripheral blood mononuclear cells from 10 other subjects were less responsive toward cryopreserved donor thymic cells than toward allogeneic cells ( P = 0.00007). Adult control peripheral blood mononuclear cells proliferated strongly in response to the donor thymic cells. Both the subjects and controls showed similar proliferative responses against allogeneic cells and phytohemagglutinin. This study provides in vitro evidence for long-term tolerance of complete DiGeorge anomaly thymus transplantation recipients toward their HLA-nonmatched thymus grafts.

Development of Regulatory T Cells After Thymus Transplantation in Subjects with Complete DiGeorge Syndrome

Development of Regulatory T Cells After Thymus Transplantation in Subjects with Complete DiGeorge Syndrome

Portal Hemodynamic Changes after Hepatocyte Transplantation in Acute Hepatic Failure

Hepatocyte transplantation has been proposed as an alternative for rescuing patients with acute hepatic failure. However, portal hemodynamic changes and issues of safety after hepatocyte transplantation in acute hepatic failure have not been systemically evaluated because of the lack of a suitable experimentation system. In this study, we created a novel spring-guidewire introducer needle to simplify the technique for long-term portal cannulation in F-344 rats. The portal cannula was capable of being used for blood sampling, infusion of hepatocytes, and measurement of portal hemodynamic changes. One week after portal cannulation, rats were injected with D-galactosamine (1.35 g/kg, i.p.) to induce hepatic failure. Hepatocytes (2 × 10⁷) were infused intraportally 24–26 h after induction of liver injury. Portal pressures were recorded for up to 60 min after hepatocyte transplantation. Intraportal infusion of 2 × 10⁷ hepatocytes caused an instantaneous onset of portal hypertension. The magnitude of the rise in portal pressure was similar in both normal rats and rats with acute hepatic failure (33.0 ± 7.1 vs. 37.7 ± 0.5 mm Hg; p = 0.23). However, the resolution rate of portal hypertension was remarkably delayed in rats with acute hepatic failure, and the portal pressure was significantly higher than that in normal rats 60 min after hepatocyte transplantation (25.0 ± 2.8 vs. 14.5 ± 2.4 mm Hg; p = 0.007). In conclusion, we have established a simple new technique for long-term portal cannulation of rats. Our studies provide critical insights into the delayed resolution of portal hemodynamics after hepatocyte transplantation in subjects with acute hepatic failure.

A Phase I/II Study of Xcellerated T Cells™ after Autologous Peripheral Blood Stem Cell Transplantation in Patients with Multiple Myeloma.

Background: Previous studies have demonstrated a correlation between survival and lymphocyte recovery following autologous transplantation in subjects with multiple myeloma and other malignancies (Porrata et al., Blood 2001). We initiated a trial in the transplant setting to evaluate the activity of T cells activated and expanded ex vivo with the Xcellerate™ Process, which uses anti-CD3 and anti-CD28 antibody-coated magnetic beads (Xcyte™ -Dynabeads®).Methods: Following induction therapy, patients underwent leukapheresis to collect peripheral blood mononuclear cells for the Xcellerate Process. Patients then underwent stem cell mobilization and collection, followed by high dose melphalan (200 mg/m2). Three days following peripheral blood stem cell infusion, subjects received 50–100 x 109 Xcellerated T Cells.Results: 36 subjects were treated. The median last f/u visit is 180 days post-transplant (range 90–450). A WaveBioreactor-based Xcellerate III Process, which was instituted in the last 18 subjects, resulted in 249 ± 90 fold (mean ± SD) T cell expansion. There were 93.6 ± 0.8 x 109 cells infused, which were 97.6 + 4.0% T cells. There were no Grade 3 or 4 acute infusional toxicities. Days of neutropenia and thrombocytopenia were 5 (3–43) and 4.5 (0–128) respectively [median (range)]. There were a median of 2 (range 0–14) units of packed red blood cell transfusions in 18/31 (58%) of subjects and a median of 0 (range 0–22) platelet transfusions in 15/31 (48%) of subjects. There were serious or Grade 3 infections in 5/29 (17%) of subjects, and mucositis in 5/29 (17%) of subjects (all ≤ Grade 2). Median days of hospitalization were 16 (range 10–70). Lymphocyte recovery was rapid, with counts reaching > 500/mm3 generally within 1–2 days following T cell infusion. Historically, lymphocyte recovery to > 500/mm3 usually does not occur for 3 or more weeks post-transplant. The rapid lymphocyte recovery included both CD4+ and CD8+ T cells. The mean (± SEM) CD4+ T cell count at 90 days post-transplant was 1,210 ± 80/mm3, significantly higher than that for historical controls receiving the same treatment regimen without Xcellerated T Cells (198 ± 72). The T cell receptor repertoire measured 25 days after the Xcellerated T Cell infusion demonstrated a normal pattern (n = 4/5). This is in contrast to the severe skewing of T cell receptor diversity observed in myeloma subjects following standard autologous stem cell transplantation (Mariani et al, BJH 2001). In 35 evaluable patients, preliminary results demonstrated 6% CRs, 46% VGPRs, 34% PRs, and 11% with PD, using the M-protein at diagnosis as reference. There have been no reported deaths to date.Conclusions: In multiple myeloma subjects, administration of Xcellerated T Cells following high-dose chemotherapy and autologous stem cell transplantation leads to rapid lymphocyte recovery and appears to restore a normal T cell receptor repertoire. The majority of subjects achieve clinical responses in the autologous transplant setting.

Portal hemodynamic changes after hepatocyte transplantation in acute hepatic failure

Hepatocyte transplantation has been proposed as an alternative for rescuing patients with acute hepatic failure. However, portal hemodynamic changes and issues of safety after hepatocyte transplantation in acute hepatic failure have not been systemically evaluated because of the lack of a suitable experimentation system. In this study, we created a novel spring-guidewire introducer needle to simplify the technique for long-term portal cannulation in F-344 rats. The portal cannula was capable of being used for blood sampling, infusion of hepatocytes, and measurement of portal hemodynamic changes. One week after portal cannulation, rats were injected with D-galactosamine (1.35 g/kg, i.p.) to induce hepatic failure. Hepatocytes (2 x 10(7)) were infused intraportally 24-26 h after induction of liver injury. Portal pressures were recorded for up to 60 min after hepatocyte transplantation. Intraportal infusion of 2 x 10(7) hepatocytes caused an instantaneous onset of portal hypertension. The magnitude of the rise in portal pressure was similar in both normal rats and rats with acute hepatic failure (33.0 +/- 7.1 vs. 37.7 +/- 0.5 mm Hg; p = 0.23). However, the resolution rate of portal hypertension was remarkably delayed in rats with acute hepatic failure, and the portal pressure was significantly higher than that in normal rats 60 min after hepatocyte transplantation (25.0 +/- 2.8 vs. 14.5 +/- 2.4 mm Hg; p = 0.007). In conclusion, we have established a simple new technique for long-term portal cannulation of rats. Our studies provide critical insights into the delayed resolution of portal hemodynamics after hepatocyte transplantation in subjects with acute hepatic failure.

The 12-min walk test as an assessment criterion for lung transplantation in subjects with cystic fibrosis

Timing for the evaluation and listing of patients with cystic fibrosis who are candidates for lung transplantation is still uncertain. Our study goal was to determine the value of the 12-min walk test as a simple and easy-to-use adjunctive assessment tool for pre-transplant evaluation. A total of 34 cystic fibrosis patients (17 male, mean age 22 years) with end-stage lung disease were evaluated in this retrospective analysis. The 12-min walk test was carried out according to an established protocol. Before walking, body plethysmography was performed and a capillary sample was taken for blood gas analysis. Walking distance and SaO2 via continuous pulse oximetry were recorded online. There was a strong correlation between survival time and walking distance (r=0.7, P=0.003). No other single parameter, such as FEV1, SaO2,pCO2 or BMI, showed a statistically significant correlation with survival time. Subjects who walked ≤700 m had a lower cumulative survival (P=0.02). There was a statistically significant positive correlation between walking distance and SaO2 at rest and after 12 min of walking (r=0.5, P=0.001; and r=0.5, P=0.04, respectively). There was no correlation between walking distance and pCO2 at rest, BMI, FEV1, or degree of change in SaO2 during the walk test. This study demonstrates that in CF patients with end-stage lung disease, walking distance during a 12-min walk test is more informative with respect to survival than single parameters such as SaO2,pCO2, FEV1 or BMI.

Transplantation of RPE in Age-related Macular Degeneration

• A study was carried out to investigate whether human RPE allografts are tolerated or rejected in the subretinal space and to determine the feasibility of RPE transplantation in subjects with age-related macular degeneration (AMD). • Methods: Patches of human fetal RPE (13–20 weeks of gestational age) were transplanted into the subretinal space of five patients after surgical removal of subfoveal fibrovascular membranes, and to four subjects with dry geographic atrophy. Suspensions of RPE cells were transplanted to four other patients with nonexudative AMD. Results were evaluated with clinical ophthalmological examination, SLO microperimetry and fluorescein angiography over 8–20 months. • Results: In disciform lesions, RPE transplants developed macular edema and fluorescein leakage concomitant with gradual reduction of visual acuity, implying host-graft rejection, over 1–6 months. In geographic atrophy, three of four transplants showed little change in shape and size after 12 months (one transplant was slowly rejected). In non-exudative AMD, RPE suspension transplants showed no evidence of rejection and were associated with the disappearance of drusen; visual acuity remained stable and SLO microperimetry confirmed retinal function over the transplanted area. • Conclusion: Human RPE allografts are not invariably rejected in the subretinal space without immunosuppression. The rejection rate is lower in nonexudative than in neovascular AMD. An intact blood-retinal barrier is likely to protect against rejection. It is technically feasible to transplant human RPE into the submacular space without adversely affecting visual function in nonexudative AMD over relatively long periods of time

Transplantation of RPE in age-related macular degeneration: Observations in disciform lesions and dry RPE atrophy

A study was carried out to investigate whether human RPE allografts are tolerated or rejected in the subretinal space and to determine the feasibility of RPE transplantation in subjects with age-related macular degeneration (AMD). Patches of human fetal RPE (13-20 weeks of gestational age) were transplanted into the subretinal space of five patients after surgical removal of subfoveal fibrovascular membranes, and to four subjects with dry geographic atrophy. Suspensions of RPE cells were transplanted to four other patients with nonexudative AMD. Results were evaluated with clinical ophthalmological examination, SLO microperimetry and fluorescein angiography over 8-20 months. In disciform lesions, RPE transplants developed macular edema and fluorescein leakage concomitant with gradual reduction of visual acuity, implying host-graft rejection, over 1-6 months. In geographic atrophy, three of four transplants showed little change in shape and size after 12 months (one transplant was slowly rejected). In non-exudative AMD, RPE suspension transplants showed no evidence of rejection and were associated with the disappearance of drusen; visual acuity remained stable and SLO microperimetry confirmed retinal function over the transplanted area. Human RPE allografts are not invariably rejected in the subretinal space without immunosuppression. The rejection rate is lower in nonexudative than in neovascular AMD. An intact blood-retinal barrier is likely to protect against rejection. It is technically feasible to transplant human RPE into the submacular space without adversely affecting visual function in nonexudative AMD over relatively long periods of time.