Including the liver in the visceral allograft: Impact on donor-specific anti-HLA antibodies and long-term outcomes.

Humoral immunity emerges as a risk factor for graft failure after visceral transplantation (VTx) and development of donor-specific anti-HLA antibodies (DSAs) has been linked with poor outcomes. In most cases, a simultaneous liver transplant can be safely performed in sensitized patients with DSA and appears protective against lymphocytotoxic antibodies. We investigated the incidence of acute (AR) and chronic rejection (CR) in 32 VTx without any B cell-depleting pre-treatment (6 isolated intestinal transplants (IT) and 26 liver-containing, multivisceral transplants (MVT) and assessed the presence of donor-specific antibodies (DSA) pre- and post-transplantation. Twenty-one patients (65 %) developed AR, 15 (57 %) of the MVT and 6 (100 %) of the IT (p = 0.05). CR occurred in 4 IT (60 %, p < 0.001). At one month, de novo DSA were present in 71 % of VTx (66 % MVT vs 100 % IT, p = 0.09). At the last available follow-up, 69 % of the MVT and 50 % of the IT patients were DSA-free. De novo DSA seemed more persistent (7/19, 37 %) than pre-Tx DSA (1/6, 17 %; p = n.s.), de novo DSA were more frequently specific for HLA class II than class I, 16/19 (84 %) vs. 7/19 (37 %; p = 0.003), and HLA-DQ was their most frequent target HLA. DQ mismatches appeared to be a risk factor for developing de novo DSA. In conclusion, liver-containing visceral allografts have superior short- and long-term outcomes compared with liver-free allografts. De novo DSA develop early and frequently after VTx performed without B cell-depleting induction therapy, but the exact role of DSA in the pathogenesis of rejection remains unclear.

Long-term Course of Kidney Function in Uterus Transplant Recipients Under Treatment With Tacrolimus and After Transplantectomy: Results of the First Clinical Cohort.

Background: Chronic kidney disease is common after non-renal solid organ transplantation, mainly secondary to calcineurin inhibitors toxicity. Uterus transplantation (UTx) is an innovative treatment for women with absolute uterine factor infertility. UTx is exclusive because it is transient with the absence of lifelong immunosuppression and is performed in young healthy participants. Therefore, UTx provides a unique setting for evaluating the effect of time-limited calcineurin inhibitors treatment on recipients' kidney function. Methods: In the first UTx cohort worldwide, we studied kidney function using estimated glomerular filtration rate (eGFR) in 7 women over a median follow-up of 121 (119-126) mo. Results: Median eGFR (mL/min/1.73 m2) of the cohort was 113 at UTx, which declined to 74 during month 3, 71 at months 10-12, 76 at hysterectomy (HE), and 83 at last follow-up. Median duration of tacrolimus exposure was 52 (22-83) mo, and median trough levels (µg/L) were 10 during month 3 and 5.8 at HE. Between UTx and month 3, decline in kidney function was observed in all 7 participants with a median eGFR slope for the whole cohort of -24 mL/min/1.73 m2, which declined further by -4 mL/min/1.73 m2 until months 10-12. Thereafter, eGFR slope improved in 3 participants, remained stable in 3, and worsened in 1 until HE/tacrolimus discontinuation, after which it improved in 2. Eventually, between UTx and last follow-up, 4 of 7 participants had a decline in their eGFR, the median annual eGFR slope being negative at -1.9 mL/min/1.73 m2/y for the whole group. Conclusions: Kidney function declined in all recipients early after UTx followed by a persistent long-term decrease in majority, despite transplantectomy and discontinuation of immunosuppression. Thus, UTx may incur an increased risk of chronic kidney disease even in this young and healthy population, highlighting the importance of close surveillance of kidney function and minimization of tacrolimus exposure.

End-ischemic hypothermic oxygenated machine perfusion does not improve renal outcome following liver transplantation from aged donors: A single-center retrospective report.

BACKGROUND: Organ transplantation using grafts from elderly donors entails a higher risk for severe ischemia-reperfusion injury (IRI). Advanced IRI after liver transplantation (LT) seems to be associated with the development of acute kidney injury (AKI). We studied if end-ischemic hypothermic oxygenated machine perfusion (HOPE) of liver grafts, aimed at mitigating liver IRI, impacts on the frequency and severity of AKI after LT. METHODS: LTs performed at our center between January 2017 and December 2022 using organs from deceased brain-dead donors aged 70 or older were reviewed. From November 2020 on, HOPE was performed routinely in this donor category. The frequency and severity of AKI (KDIGO criteria) within 48 hours of graft reperfusion and the model of early allograft function (MEAF) were compared between HOPE-LTs (n = 30) and control LTs (n = 71). RESULTS: AKI developed in 23/30 (77%) HOPE-LTs and in 40/71 (56%) control LTs (p = n.s.), with no difference in severity and timing between groups. Renal replacement therapy was required in 3/30 (10%) HOPE-LTs and 6/71 (8%) control LTs. In addition, transaminase leak during the first week (marker of IRI) and MEAF were similar between groups. These findings persisted after propensity matching. Histology showed more hepatocyte vacuolization and higher Suzuki score in HOPE-LTs. Although this analysis could have been underpowered, no trends supporting the benefit of HOPE on liver and renal injury after LT were ever identified. CONCLUSIONS: In conclusion, HOPE in this group of older donors does not seem to improve either graft IRI, or the incidence of early AKI after LT.

Liver Graft Proteomics Reveals Potential Incipient Mechanisms behind Early Renal Dysfunction after Liver Transplantation.

Acute kidney injury (AKI) is frequent after liver transplantation (LT) and correlates with later development of chronic kidney disease. Its etiology is multifactorial and combines pre-, intra-, and postoperative factors. Additionally, the liver graft itself seems an important element in the development of AKI, yet the detailed mechanisms remain unclear. We hypothesized that grafts of LT recipients developing significant early AKI may show distinct proteomic alterations, and we set out to identify proteome differences between LT recipients developing moderate or severe AKI (n = 7) and LT recipients without early renal injury (n = 7). Liver biopsies obtained one hour after reperfusion were assessed histologically and using quantitative proteomics. Several cytokines and serum amyloid A2 (SAA2) were analyzed in serum samples obtained preoperatively, 2−4 h, and 20−24 h after graft reperfusion, respectively. LT induced mild histological alterations without significant differences between groups but uniformly altered liver function tests peaking on postoperative day 1, with a trend towards more severe alterations in patients developing AKI. Global quantitative proteomic analysis revealed 136 proteins differing significantly in their expression levels (p < 0.05, FC 20%): 80 proteins had higher and 56 had lower levels in the AKI group. Most of these proteins were related to immune and inflammatory responses, host defense, and neutrophil degranulation. No differences between the studied pro- and anti-inflammatory cytokines or SAA2 between groups were found at any moment. Our results suggest that grafts of LT patients who develop early AKI reveal a distinct proteome dominated by an early yet prominent activation of the innate immunity. These findings support the hypothesis that AKI after LT may be favored by certain graft characteristics.

Perioperative kidney injury in liver transplantation: a prospective study with renal histology and measured glomerular filtration rates.

BACKGROUND: Acute kidney injury (AKI) is frequent after liver transplantation (LT), with impact on graft function, morbidity and mortality. Although multifactorial, the pathophysiology of perioperative kidney injury remains unclear. Our aims were to analyze the frequency, evolution and risk factors for kidney impairment during the peri- and early post-operative period. METHODS: In a prospective, single-center study of 27 adult patients undergoing first single-organ LT, we analyzed measured glomerular filtration rate (mGFR) pre-transplant, at post-operative day (POD) 10, and at 1, 3, 12 and 36 months. Kidney and liver graft biopsies were performed during LT. RESULTS: A median mGFR decline of 45% was detected from pre-transplant to POD 10, correlating strongly with the mGFR evolution from baseline to 12 months (rs = 0.80, p<.001) and baseline to 36 months (rs = 0.82, p<.001). AKI occurred in 59% of recipients within 48 h of LT, notably before the introduction of calcineurin inhibitors on POD 3. AKI was strongly associated with mGFR at 12 and 36 months. Kidney and liver graft biopsies showed only minor histological changes. Donor and recipient body mass index, recipient age, model of end-stage liver disease score, diagnosis of hepatitis C, donor cause of death, as well as bleeding, transfusions and duration of the anhepatic phase correlated with early kidney dysfunction. CONCLUSION: The greatest decline in mGFR was evident within 10 days and AKI within hours of LT, irrespective of baseline mGFR and before introduction of calcineurin inhibitors. Very early post-LT kidney injury has substantial consequences for long-term kidney function.

Endoscopic ultrasound in the monitoring of the intestinal allograft.

OBJECTIVE: Chronic rejection (CR) of the small intestinal allograft includes mucosal fibrosis, bowel thickening and arteriopathy in the outer wall layers and the mesentery. CR lacks non-invasive markers and reliable diagnostic methods. We evaluated endoscopic ultrasound (EUS) as a novel approach for monitoring of the intestinal allograft with respect to CR. DESIGN: In intestinal graft recipients, EUS and enteroscopy with ileal mucosal biopsy were performed via the ileostomy. At EUS, the wall thickness of the intestinal graft was measured in standard mode, whereas the resistive index (RI) of the supplying artery was assessed in pulsed Doppler mode. At enteroscopy, the intestinal mucosa was assessed. Findings were compared with histopathology and clinical follow-up. RESULTS: EUS was successfully performed in all 11 patients (adequate clinical course (AC) n=9; CR n=2) after a median interval of 1537 days (range: 170-5204), post-transplantation. The total diameter of the wall (layer I-V) was comparable in all patients. Meanwhile, the diameter of the outermost part (layer IV-V; that is, muscularis propria-serosa) was among the two CR patients (range: 1.3-1.4 mm) in the upper end of measurements as compared with the nine AC patients (range: 0.5-1.4 mm). The RI was >0.9 in both CR patients, while the RI was ≤0.8 in all AC patients. Both CR patients had abnormal findings at enteroscopy and histopathology and deceased during follow-up. CONCLUSION: EUS is a promising tool providing detailed information on the intestinal graft morphology and rheology, which may be used for assessment of potential CR in long-term follow-up of intestinal allograft recipients.

Renal function after liver transplantation: Real-world experience with basiliximab induction and delayed reduced-dose tacrolimus.

BACKGROUND: Routine use of delayed reduced-dose calcineurin-inhibitor treatment with induction immunosuppression in liver transplantation to minimize post-operative kidney injury is still scarce. AIM: To evaluate real-world experience of basiliximab induction with delayed reduced-dose tacrolimus. METHODS: In a retrospective cohort study, kidney function was evaluated pre- and postoperatively by measured glomerular filtration rate (mGFR). Adult patients undergoing liver transplantation between 2000 and 2017 were divided into a conventional treatment group (immediate-introduction of tacrolimus, target trough levels 10-15 ng/mL, and corticosteroids, n = 203) and a revised treatment group (basiliximab induction, reduced-dose tacrolimus, target through levels 5-8 ng/mL, delayed until day three, and mycophenolate mofetil 2000 mg/day, n = 343). RESULTS: Mean mGFR was similar between groups at wait-listing (85.3 vs 84.1 ml/min/1.73m², p = 0.60), but higher in the revised treatment group at 3 (56.8 vs 63.4 ml/min/1.73m², p = 0.004) and 12 months post-transplant (60.9 vs 69.7 ml/min/1.73m², p<0.001); this difference remained after correcting for multiple confounders and was independent of pre-transplant mGFR. In the revised treatment group, biopsy proven acute rejection rate was lower (38% vs. 21%, p<0.001), and graft-survival better (p = 0.01). CONCLUSION: Basiliximab induction with delayed reduced-dose tacrolimus is associated with less kidney injury when compared to standard-dose tacrolimus, without increased risk of rejection, graft loss or death.

Excellent outcome following emergency deceased donor ABO-incompatible liver transplantation using rituximab and antigen specific immunoadsorption.

BACKGROUND: The acceptance of ABO-incompatible (ABOi) liver grafts will expand the donor pool for a patient in urgent need for a liver transplantation (LT). Here we report our results with emergency ABOi DD (deceased donor) LT using rituximab and antigen specific immunoadsorption. PATIENTS AND METHODS: 2009 to 2019 we performed 20 ABOi DD LTs (adults n = 17, children n = 3) for patients in urgent need for a LT. Immunosuppression consisted of rituximab (n = 20) and basiliximab (n = 15) or anti-thymocyte globuline (n = 4), intravenous immunoglobulin (IVIG; n = 6), tacrolimus, prednisolone and mycophenolate mofetil. Fifteen patients were treated with IA (n = 14) or both IA and plasmapheresis (PP; n = 1) pre-transplant and 18 patients were treated with IA (n = 15) or both IA and PP (n = 3) post-transplant. The median pre-transplant MELD- score was 40 (range 18-40). Patient and graft survival and complications were compared to a 1:4 case matched control group of ABO-identical or compatible (ABOid/c) DDLT. RESULTS: The 1-, 3- and 5-year patient and graft survival rates were 85, 85 and 78% for the ABOi recipients and not significantly different compared to ABOid/c controls. Only one ABOi patient developed antibody-mediated rejection. CONCLUSION: Patient and graft survival after emergency ABOi DDLT using rituximab and immunoadorption was equal to ABOid/DDLT. ABOi DD LT was a successful approach to expand the donor pool for patients in urgent need for a liver graft.

Everolimus and long-term decline in renal function after liver transplantation: real-life experience with measured GFR.

Switching from calcineurin-inhibitors (CNI) to everolimus >6-12-months after liver transplantation (LT) seems inefficient in improving renal function, but whether everolimus halts further renal-function decline compared to low-dose CNI remains unclear. In a retrospective single-center study of everolimus after LT (2008-2016) with routine measured glomerular filtration rates (mGFR; 51Cr-EDTA- or iohexol clearance), we compared by propensity-score matching everolimus therapy to low-dose CNI therapy. The study comprised 36 patients with everolimus introduced on average 22 months post-LT (range 2-105 months, median follow-up 3.4 years), and 36 matched controls. Everolimus introduction was associated with a mean improvement in mGFR of 7 mL/min up to 1 year (p = .003), restricted to patients switched <1-year post-transplant and at tacrolimus trough levels >5 ng/mL. The differences between the everolimus group and controls in delta-mGFR from baseline to 1 year (7.3 vs 4.3 mL/min, p = .25) or 1-year to last follow-up (-0.8 vs -0.2 mL/min/year, p = .71) were non-significant. Proportions with mGFR decline >3 mL/min/year were similar between groups (11% and 14%, p = 1.00). Everolimus was stopped in three patients (8%), and acute rejection occurred in 17%. In conclusion, despite an early improvement in renal function after everolimus introduction, we found no evidence that everolimus halts the long-term mGFR decline compared to continued low-dose CNI therapy. Due to retrospective design, small sample size and heterogenous characteristics, definite conclusions require prospective studies.

Notice of Retraction: Inappropriate Image Duplication in "Recellularization of Acellular Human Small Intestine Using Bone Marrow Stem Cells".

STEM CELLS TRANSLATIONAL MEDICINE 2013;2:307-315; http://dx.doi.org/10.5966/sctm.2012-0108 The above-referenced article published on March 13, 2013 in Stem Cells Translational Medicine has been retracted by agreement between the Journal Editors and co-publishers, AlphaMed Press and Wiley Periodicals, Inc. The retraction has been agreed to with acknowledgment of problems with Figure 3, which we believe make some of the data unreliable.

Life of patients 10 years after a successful pediatric intestinal transplantation in Europe.

A multicenter Europe-wide single-point study in intestinal transplantation (ITx) centers was conducted to identify and describe patients surviving for more than 10 years after ITx in childhood. The health and nutritional status, care requirements and psychosocial status were recorded. Among 120 transplanted before 2005, 38 patients with a functioning graft were included. Thirty (79%) had an exclusive oral diet, seven (18%) complimentary enteral nutrition for eating disorders, and one a combination of parenteral and enteral nutrition. They received a median of five drugs daily and five had a stoma. We did not observe any catch-up growth during the 10 years of follow-up. In the previous five years, 22 patients needed unplanned hospitalization with a median in-patient stay of six days. Eleven needed ongoing psychiatric follow-ups, and nine needed other specialist follow-ups. An increasing independency from parents was seen after the age of 18, with three having a stable employment and 31 pursuing education. Despite a good graft function, growth may not catch up. The burden of medical care remains high in the long term. This has to be closely followed in a multidisciplinary setting to improve long-term quality of life in these patients.

The endoscopic surveillance of the transplanted small intestine: a single center experience and a proposal for a grading score.

OBJECTIVE: Microscopic examination of endoscopic biopsies forms the basis of acute cellular rejection (ACR) monitoring after intestinal transplantation (ITx). The endoscopy findings during acute rejection (AR) are known but a grading system for its severity is lacking. We designed and implemented a five-stage grading score based on acknowledged endoscopic features of AR, to allow a faster preliminary diagnosis of AR and intra- and interpatient comparisons. METHODS: Two investigators reviewed and graded the endoscopy reports after 28 ITx using a novel score and correlated the results with pathology findings. RESULTS: We reviewed 512 ileoscopies: 370 examinations (74%) were normal (G0), 59 had mild alterations (erythema, edematous villi-G1) and 36 showed moderate changes (erosions, blunted villi-G2); 17 ileoscopies revealed advanced changes (ulcerations, villus loss-G3). In 18 endoscopies the changes were severe (mucosal loss-G4). Inter-reviewer agreement was very good (kappa = 0.81). Biopsies from 86 endoscopy sessions (17%) indicated ACR with 63 cases having moderate or severe ACR. For mild ACR the sensitivity of the score was 29% and the specificity was 86% whereas the positive (PPV) and negative predictive values (NPVs) were 14% and 93% respectively. During advanced ACR the sensitivity and specificity were 92% and 86%, respectively whereas the PPV and NPV were 49% and 98% respectively. CONCLUSIONS: Endoscopy alone has a limited ability to reliably diagnose intestinal ACR. We suggest a novel grading score summarizing ACR findings and allowing comparisons between intestinal graft endoscopies.

Initial Experience of Video Capsule Endoscopy After Intestinal Transplantation.

BACKGROUND: Intestinal transplantation is a procedure which inflicts immunological and infectious complications that affect the transplanted graft, posing both diagnostic and therapeutic challenges. Video capsule endoscopy (VCE) offers easy access to the entire small intestine and presents itself as an interesting option. However, at present, no studies evaluating the usefulness of video capsule endoscopies in this setting have been published. Our aim was to evaluate the usefulness of VCE in detecting complications that arise after intestinal transplantation. METHODS: We included 7 adult patients with either isolated intestine (n = 1) or multivisceral grafts (n = 6). These patients underwent 12 VCE between 2004 and 2015 at the Sahlgrenska University Hospital. The median age was 42 (21-67) years (4 women/3 men). VCE was used in clinical situations where the conventional diagnostic methods failed to provide answers to the clinical question. RESULTS: Indications for the procedure were: suspicion of rejection (n = 4 examinations), gastrointestinal dysmotility (n = 4 examinations), high stomal output (n = 2 examinations), suspicion of lymphoproliferative disease in the transplanted graft (n = 1 examination), and clinical surveillance (n = 1 examination). The median time after transplantation for performing an examination was 740 (26-3059) days. VCE was useful in 83% of the examinations and the results influenced the planned management. The overall agreement between VCE findings and biopsies was moderate (κ = 0.54, P = 0.05) but increased when comparing the presence of inflammation/rejection (κ = 0.79, P < 0.001). CONCLUSIONS: VCE is a promising diagnostic method after intestinal transplantation. However, larger studies are needed to evaluate its potential risks and gains.

Recipient Hyperbilirubinemia May Reduce Ischemia-Reperfusion Injury but Fails to Improve Outcome in Clinical Liver Transplantation.

Background. Exogenous bilirubin may reduce experimental ischemia-reperfusion injury (IRI) due to its antioxidant properties. We studied if early graft exposure to high bilirubin levels in the recipient affects the early IRI and outcomes after liver transplantation (LTx). Methods. In 427 LTx patients, the AUROC curve based on bilirubin and AST at day 1 identified a cutoff of 2.04 mg/dL for the recipient pretransplant bilirubin. Recipients were grouped as having low (group L, n = 152) or high (group H, n = 275) bilirubin. Both groups had similar donor-related variables (age, preservation time, donor BMI > 28, and donor risk index (DRI)). Results. Alanine (ALT) and aspartate (AST) aminotransferase levels were higher in group L at day 1; ALT levels remained higher at day 2 in group L. LTx from high risk donors (DRI > 2) revealed a trend towards lower transaminases during the first two days after transplantation in group H. One month and 1-year patient survival were similar in groups L and H. High preoperative bilirubin did not affect the risk for early graft dysfunction (EGD), death, or graft loss during the first year after transplantation nor the incidence of acute rejection. LTx using donors with DRI > 2 resulted in similar rates of EGD in both groups. Conclusion. Increased bilirubin appears to reduce the early IRI after LTx yet this improvement was insufficient to improve the clinical outcome.

Fifteen years' experience of intestinal and multivisceral transplantation in the Nordic countries.

OBJECTIVE: Intestinal and multivisceral transplantation have gained acceptance as treatment modalities for patients with: intestinal failure and life-threatening complications of parenteral nutrition (PN), rare cases of vascular abdominal catastrophes and selected cases of low-grade neoplastic tumors such as neuroendocrine pancreatic tumors and desmoids involving the mesenteric root. The aim was to describe the survival and nutritional outcome in the transplanted Nordic patients and the complications attributed to this procedure. METHOD: The authors included all Nordic patients transplanted between January 1998 and December 2013. Information on patients transplanted outside the Nordic region was collected through questionnaires. RESULTS: A total of 34 patients received different types of intestinal allografts. Currently, there are two Nordic transplant centers (n = 29) performing these procedures (Gothenburg, Sweden n = 24, Helsinki, Finland n = 5). The remaining five patients were transplanted in the USA (n = 3) and the UK (n = 2). Most patients were transplanted for life-threatening failure of PN (70%) caused primarily by intestinal motility diseases (59%). Allograft rejection was the most common complication and occurred in 79% of the patients followed by post-transplantation lymphoproliferative disorders (21%) and graft-versus-host disease (18%). The 1- and 5-year survival was 79% and 65% respectively for the whole cohort and nutritional autonomy was achieved in 73% of the adults and 57% of the children at 1 year after transplantation. CONCLUSION: This collective Nordic experience confirms that intestinal transplantation is a complex procedure with many complications, yet with the possibility to provide long-term survival in selected conditions previously considered untreatable.

Survival of patients evaluated for intestinal and multivisceral transplantation - the Scandinavian experience.

OBJECTIVE: The current treatment of choice for patients with intestinal failure is parenteral nutrition, whereas medical therapy or resection is preferred for patients with neuroendocrine pancreatic tumors (NEPT) along with liver metastasis. As the survival of patients undergoing intestinal and multivisceral transplantation is improving, the discussion for expansion of treatment options has become a subject of debate. The aim was to investigate the outcome for patients referred for intestinal and multivisceral transplantation and to determine which patient group are the ones most likely to benefit the most from transplantation. METHODS: The authors included all patients evaluated for intestinal and multivisceral transplantation at the Sahlgrenska University Hospital and The Queen Silvia Children's Hospital center between February 1998 and November 2009. Patients were classified according to proposed treatment strategy, and the outcome was evaluated. RESULTS: A total of 43 adults and 19 children with either intestinal failure or NEPT with liver metastases were evaluated for transplantation. Of these patients, 15 adults and 5 children were transplanted. Transplantation was lifesaving for most children - all the children survived after transplantation, but 70% (4/6) died while awaiting transplantation. Among the adult patients with intestinal failure, the survival rate for patients considered to be stable on parenteral nutrition was higher than the transplanted adult patients. The survival rate of patients with NEPT was similar to the results seen among patients transplanted for intestinal failure. CONCLUSION: The results confirm the poor prognosis of patients with intestinal failure awaiting transplantation and indicate that different transplantation criteria may be applied for adults and children, especially when early transplantation is the preferred treatment. The role of multivisceral transplantation in patients with NEPT remains uncertain.

Recellularization of acellular human small intestine using bone marrow stem cells.

We aimed to produce an acellular human tissue scaffold with a view to test the possibility of recellularization with bone marrow stem cells to produce a tissue-engineered small intestine (TESI). Human small-bowel specimens (n = 5) were obtained from cadaveric organ donors and treated sequentially with 6% dimethyl sulfoxide in hypotonic buffer, 1% Triton X-100, and DNase. Each small intestine (SI) piece (6 cm) was recellularized with EPCAM+ and CD133+ allogeneic bone marrow stem cells. Histological and molecular analysis demonstrated that after decellularization, all cellular components and nuclear material were removed. Our analysis also showed that the decellularized human SI tissue retained its histoarchitecture with intact villi and major structural proteins. Protein films of common extracellular matrix constituents (collagen I, laminin, and fibronectin) were found in abundance. Furthermore, several residual angiogenic factors were found in the decellularized SI. Following recellularization, we found viable mucin-positive goblet cells, CK18+ epithelial cells in villi adjacent to a muscularis mucosa with α-actin+ smooth muscle cells, and a high repopulation of blood vessels with CD31+ endothelial cells. Our results show that in the future, such a TESI would be ideal for clinical purposes, because it can be derived from the recipient's own immunocompatible bone marrow cells, thus avoiding the use of immunosuppression.