Graft Survival Research Articles

The effect of exogenous mitochondria in enhancing the survival and volume retention of transplanted fat tissue in a nude mice model

BackgroundDespite the pivotal role of fat grafting in plastic, reconstructive, and aesthetic surgery, inconsistent survival rates of transplanted adipose tissue, primarily due to early ischemic and hypoxic insults, remain a significant challenge. The infusion of healthy mitochondria has emerged as a promising intervention to support tissue recovery from ischemic, hypoxic, and other types of damages across various organ systems.ObjectivesThis study aims to evaluate the impact of supplementing human adipose tissue grafts with healthy exogenous mitochondria on their volume and mass retention rates when transplanted into the subcutaneous layers of nude mice. This approach seeks to improve and optimize fat grafting techniques.MethodsHuman adipose tissues were preconditioned with exogenous mitochondria (10 µg/mL), a combination of exogenous mitochondria and the inhibitor Dyngo-4a, Dyngo-4a alone, or PBS, and then transplanted into the subcutaneous tissue of 24 nude mice. Samples were harvested at 1 and 3 months post-transplantation for analysis of mass and volume retention. The structural morphology and integrity of the adipose tissues were assessed using Hematoxylin and Eosin (H&E) staining.ResultsMitochondrial preconditioning significantly enhanced the retention of mass and volume in fat grafts, demonstrating superior structural morphology and integrity compared to the control group.ConclusionsThis study highlights the potential of exogenous mitochondrial augmentation in fat transplantation to significantly improve fat graft survival, thereby optimizing the success of fat grafting procedures.

Improved graft survival by using three-dimensional printing of intra-abdominal cavity to prevent large-for-size syndrome in liver transplantation.

While large-for-size syndrome is uncommon in liver transplantation (LT), it can result in fatal outcome. To prevent such fatality, we manufactured 3D-printed intra-abdominal cavity replicas to provide intuitive understanding of the sizes of the graft and the patient's abdomen in patients with small body size between July 2020 and February 2022. Clinical outcomes were compared between patients using our 3D model during LT, and patients who underwent LT without 3D model by using 1 : 5 ratio propensity score-matched analysis. After matching, a total of 20 patients using 3D-printed abdominal cavity model and 100 patients of the control group were included in this study. There were no significant differences in 30-day postoperative complication (50.0% vs. 64.0%, p = 0.356) and the incidence of large-for-size syndrome (0% vs. 7%, p = 0.599). Overall survival of the 3D-printed group was similar to that of the control group (p = 0.665), but graft survival was significantly superior in the 3D-printed group, compared to the control group (p = 0.034). Since it showed better graft survival, as well as low cost and short production time, our 3D-printing protocol can be a feasible option for patients with small abdominal cavity to prevent large-for-size syndrome after LT.

Infective endocarditis with metastatic infections in a renal transplant recipient: a case report

BackgroundInfective endocarditis is an uncommon but well-known post-transplant complication with significant morbidity and mortality. It has been observed to be about 171 times more common in solid organ transplant patients than in the general population. With the increasing rate of end-stage kidney disease, the higher demand for kidney transplantation with better graft survival, and life expectancy rates, more transplant recipients may develop infective endocarditis as a late post-transplant complication. Prompt diagnosis of infective endocarditis is therefore necessary to avert graft loss and other life-threatening outcomes.Case presentationWe present a case of a 52-year-old African patient who had a live donor kidney transplant 18 months prior to presentation and had been on oral tacrolimus 5 mg every morning/4.5 mg every evening, mycophenolic acid (MPA) 720 mg twice daily, and oral prednisolone 10 mg daily as maintenance immunosuppressive medications. Regarding the above immunosuppressive medications, he had been in good health and had a functioning transplant graft. He presented with a resolving right thigh swelling, recurrence of fever, new onset left hemiplegia, and seizures. Enterococcus faecalis infective endocarditis was diagnosed with metastatic brain abscesses, which was treated with intravenous vancomycin and gentamycin for 5 weeks. There are very few reported cases of infective endocarditis due to Enterococcus faecalis, and this case is unique because the initial presentation was pyomyositis.ConclusionInfective endocarditis with septic embolization to the brain should be considered in kidney transplant recipients with pyomyositis and multiple rim-enhancing lesions, especially in the late post-transplant period with Enterococcal spp. as an emerging cause of infective endocarditis in kidney transplant recipients. Clinicians will need to have a high index of suspicion to aid early diagnosis with appropriate treatment to prevent adverse outcomes.

Outcomes After Osteochondral Allograft Transplantation of the Medial Femoral Condyle in Patients With Varus and Nonvarus Alignment

Background: Fresh osteochondral allograft (OCA) transplantation is an effective technique for the treatment of focal chondral and osteochondral defects in the knee. Coronal-plane malalignment leads to increased contact forces within a compartment and subsequently the cartilage repair site and may lead to higher failure rates. However, the magnitude of the effect of coronal-plane malalignment on graft survivorship and clinical outcomes has not been well characterized. Purpose: To evaluate how varus malalignment affects graft survival and patient-reported outcomes after isolated OCA transplantation of the medial femoral condyle (MFC). Study Design: Cohort study; Level of evidence, 3. Methods: A total of 70 patients (74 knees) who underwent primary OCA transplantation of the MFC between 2005 and 2019 were identified from a prospectively collected single-surgeon cartilage registry with a minimum 2-year follow-up. Coronal-plane alignment was evaluated utilizing standing hip-to-ankle radiographs. OCA failure, defined as removal of the graft or conversion to arthroplasty, and reoperations were recorded. Patient-reported outcomes were obtained preoperatively and postoperatively using the International Knee Documentation Committee score, Knee injury and Osteoarthritis Outcome Score, modified Merle d’Aubigné–Postel score, and overall patient satisfaction score. Results: The mean mechanical tibiofemoral angle for patients with varus alignment was 3.9° of varus (range, 1.1° to 8.9°) and for patients with nonvarus alignment it was 0.02° of valgus (range, 3.6° varus to 4.6° valgus). Graft survivorship was 95.3% in the varus group and 95.8% in the nonvarus group (P = .918) at 5 years postoperatively. Reoperations after OCA transplantation occurred in 14.0% of the varus group and 22.6% of the nonvarus group (P = .336). The mean International Knee Documentation Committee total score improved from 45.2 preoperatively to 74.8 at latest follow-up in the varus group and from 40.5 preoperatively to 72.3 at latest follow-up in the nonvarus group. Patient satisfaction was >85%. Conclusion: Patients undergoing isolated OCA transplantation of the MFC had high rates (>90%) of graft survivorship and significant improvements in pain and function. Patients with mild preexisting varus malalignment were found to have no difference in the failure rate or clinical outcomes compared with patients with nonvarus alignment.

Torque Teno Virus Loads as a Marker of Immunosuppression in Pediatric Kidney Transplant Recipients.

Long-term renal function and survival after kidney transplantation rely on appropriate immunosuppressive treatment to prevent the risk of rejection. New biomarkers are needed to accurately assess the degree of immunosuppression in renal transplant recipients in order to avoid organ rejection and the development of opportunistic infections. Highly prevalent in humans, torque teno virus (TTV), which belongs to the family Anelloviridae, is a small, nonenveloped, single-stranded DNA virus which has not been linked with any specific human illness, but which constitutes a major component of the human virome. Host antiviral responses allow TTV levels to be controlled; however, viral persistence remains, explaining the high prevalence in human populations, including healthy individuals. Important confounders of TTV load include time since transplantation, age, gender, obesity, and smoking status. TTV-based guidance of immunosuppressive drug dosing could help with risk stratification, reducing the risk of infection, graft rejection and oncologic disease on an individual level, enabling long-term patient and graft survival. Original studies were accessed by a systematic search from electronic databases including PubMed, ScienceDirect and Wiley Online Library. The presented data mainly derive from adult transplant recipients showing an association between TTV plasma levels and the immune status of the host: High-TTV load and high immunosuppression are associated with a risk of infection, and low-TTV load and low immunosuppression indicate a risk of rejection. However, there is minimal information on pediatric transplant recipients with further research required in this cohort. To date, it has been demonstrated that longer posttransplant times are significantly associated with lower TTV levels in children with renal transplant. Meanwhile, an association between lower TTV loads and increased risk of graft reject during the first year of transplantation was also reported. More recently, Eibensteiner etal. revealed a robust, independent association between TTV plasma load and the onset of Cytomegalovirus and BK virus infections. Data from randomized controlled trials are still missing, even in adults, but a multicenter randomized controlled trial for TTV-guided immunosuppression in adult kidney recipients (TTVguideIT) began in 2022. There is, therefore, great promise for TTV levels to be used as a biomarker that could potentially improve both graft and patient survival in transplantation.

Outcomes of Older Primary Kidney Transplant Recipients by Induction Agent and High-risk Viral Discordance Status in the United States.

The impact of induction type or high-risk viral discordance on older kidney transplant recipients is unclear. Herein, we analyzed the association between induction type, viral discordance, and outcomes for older recipients. We analyzed the Scientific Registry of Transplant Recipients standard analysis file for all primary kidney transplant recipients older than 55 y who were transplanted between 2005 and 2022. All transplants were crossmatch negative and ABO-compatible. Recipients were discharged on tacrolimus and mycophenolate ± steroids. Recipients were categorized into 3 groups by induction received: rabbit antithymocyte globulin (r-ATG; N = 51 079), interleukin-2 receptor antagonist (IL-2RA; N = 22 752), and alemtuzumab (N = 13 465). Kaplan-Meier curves were generated for recipient and graft survival, and follow-up was censored at 10 y. Mixed-effect Cox proportional hazard models examined the association between induction type, high-risk viral discordance, and outcomes of interest. Models were adjusted for pertinent recipient and donor characteristics. Induction type did not predict recipient survival in the multivariable model, whereas Epstein-Barr virus high-risk discordance predicted 14% higher mortality (1.14 [1.07-1.21], P < 0.01). In the multivariable model for death-censored graft survival, alemtuzumab, but not IL-2RA, was associated with an increased risk of graft loss (1.18 [1.06-1.29], P < 0.01) compared with r-ATG. High-risk cytomegalovirus discordance predicted 10% lower death-censored graft survival (1.10 [1.01-1.19], P < 0.02). Live donor and preemptive transplantation were favorable predictors of survival. In this large cohort of older transplant recipients, alemtuzumab, but not IL-2RA, induction was associated with an increased risk of graft loss compared with r-ATG. Cytomegalovirus and Epstein-Barr virus high-risk viral discordance portended poor graft and recipient survival, respectively.

Pseudochamber-Protected Keratoplasty (PPK) with a New Inter-Corneal Surgical Device Implant Technique in High-Risk Cases.

Background/Objectives: To describe the pseudochamber-protected keratoplasty (PPK) procedure with the new Endo-K Pro® implant technique and report the clinical outcomes in patients at high risk for penetrating keratoplasty (PKP). Methods: This case series study included patients who required a PKP and had a high risk for corneal transplant failure. All cases underwent the PPK procedure with simultaneous Endo-K Pro® implantation and had a minimum follow-up of 12 months. Graft survival was the primary outcome (defined as a clear graft with an endothelial cell density >500 cells/mm2). Central corneal thickness (CCT), corrected distance visual acuity (CDVA), intraocular pressure (IOP), and complication rate were the secondary outcomes. Results: Twenty-five eyes (twenty-five patients) were included. The mean follow-up was 23.64 ± 8.2 months (range: 12-36 months). Graft survival was achieved in 23 of the 25 cases (92%). One eye had to be re-transplanted due to persistent oedema secondary to uncontrolled IOP. In two cases (8%), the graft failed three months after surgery when an anterior pseudochamber collapsed due to direct contact of donor endothelium and host tissue. Six eyes experienced host tissue protrusion that was successfully managed using an Nd: YAG laser (two eyes) or injecting a cohesive viscoelastic into the pseudochamber (four eyes). CDVA increased significantly during the follow-up period. No significant changes were found in IOP. No intra- or postoperative complications were reported. Conclusions: PPK with the Endo-K Pro® implant seems to be an effective and safe surgical approach as an alternative in high-risk patients for PKP, allowing full-thickness corneal transplantation without performing an open-sky procedure.

Failure to Rescue Pediatric Recipients of Living Donor Liver Transplantation: A Single-Center Study of Technical Complications in 500 Primary Grafts.

The concept of failure to rescue (FTR) has been used to evaluate the quality of care in several surgical specialties but has not been well-studied after living donor liver transplantation (LDLT) in children. This study retrospectively reviewed 500 pediatric LDLT performed at a single center between 1993 and 2022. The recipient outcomes were assessed by means of patient and graft survival rates, retransplantation rates, and arterial/portal/biliary complication rates. Graft and patient losses secondary to these complications were calculated regarding FTR for patients (FTRp) and grafts (FTRg). Overall 1- and 5-year patient survival rates were 94.5% and 92.1%, respectively, the corresponding figures for graft survival being 92.7% and 89.8%. One-year hepatic artery complication rate was 3.6% (n = 18 cases), the respective rates for portal vein complications and biliary complications being 5.7% (n = 57) and 15.6% (n = 101). One-year FTRp rates for hepatic artery thrombosis, portal vein thrombosis, anastomotic biliary stricture, and intrahepatic biliary stricture were 28.6%, 9.4%, 3.6%, and 0%, respectively. The corresponding FTRg rates being 21.4%, 6.3%, 0%, and 36.4%. Such novel analytical method may offer valuable insights for optimizing quality of care in pediatric LDLT.

Innovative Strategies for Liver Transplantation: The Role of Mesenchymal Stem Cells and Their Cell-Free Derivatives.

Despite being the standard treatment for end-stage liver disease, liver transplantation has limitations like donor scarcity, high surgical costs, and immune rejection risks. Mesenchymal stem cells (MSCs) and their derivatives offer potential for liver regeneration and transplantation. MSCs, known for their multipotency, low immunogenicity, and ease of obtainability, can differentiate into hepatocyte-like cells and secrete bioactive factors that promote liver repair and reduce immune rejection. However, the clinical application of MSCs is limited by risks such as aberrant differentiation and low engraftment rates. As a safer alternative, MSC-derived secretomes and extracellular vesicles (EVs) offer promising therapeutic benefits, including enhanced graft survival, immunomodulation, and reduced ischemia-reperfusion injury. Current research highlights the efficacy of MSC-derived therapies in improving liver transplant outcomes, but further studies are necessary to standardize clinical applications. This review highlights the potential of MSCs and EVs to address key challenges in liver transplantation, paving the way for innovative therapeutic strategies.

Kidney Transplant Outcome Following Donation After Euthanasia.

In the Netherlands, organ donation after euthanasia (donation after circulatory death type V [DCD-V]) has been increasingly performed since 2012. However, the outcomes of DCD-V kidney grafts have not been thoroughly investigated. It is critical to assess the outcomes of these kidney grafts to ascertain whether DCD-V is a safe and valuable way to increase the kidney donor pool. To investigate the outcomes of DCD-V kidney transplantation and compare them with outcomes of kidney transplantation after circulatory death after withdrawal of life-sustaining therapies (DCD type III [DCD-III]) and donation after brain death (DBD). A retrospective cohort study was conducted using the database from the Dutch Transplant Foundation. All kidney transplants in the Netherlands between January 2012 (start of the euthanasia program) and July 2023 were included. Follow-up was obtained through 5 years after transplantation. Data analysis was performed from November 2023 until February 2024. Kidney transplantation with a DCD-V graft compared with DCD-III and DBD grafts. The primary outcome was death-censored graft survival until 5 years after transplantation. Secondary outcomes were the incidence of delayed graft function (DGF), permanent nonfunction (PNF), serum creatinine concentration, and patient survival until 5 years after kidney transplantation. A total of 145 DCD-V kidney transplants were compared with 1936 DCD-III and 1255 DBD kidney transplants. Median (IQR) recipient age was 59 (46-66) years in the DCD-V cohort, compared with 61 (50-68) years in the DCD-III cohort and 61 (50-68) years in the DBD cohort. The incidence of DGF with DCD-V kidney transplants (26%) was significantly less than that with DCD-III kidney transplants (49%; P < .001) and similar to that with DBD kidney transplants (22%; P = .46). PNF occurrence with DCD-V kidneys (6%) was similar to that with DCD-III kidneys (6%; P = .79) and higher than in DBD kidneys (4%; P < .001). There was no difference in 5-year death-censored graft survival between DCD-V grafts (82%) and DCD-III (86%; P = .99) or DBD (84%; P = .99) grafts. There was no difference in 5-year patient survival between DCD-V kidney transplants (69%) and DCD-III (76%; P = .45) or DBD (73%; P = .74) kidney transplants. A propensity score analysis was performed to match the DCD-V and DCD-III cohort, showing results similar to those of the unmatched cohort. This study found that DCD-V kidney transplantation yielded a lower incidence of DGF compared with DCD-III kidney transplantation and yielded long-term results similar to those of DCD-III and DBD kidney transplantation. The findings suggest that DCD-V is a safe and valuable way to increase the kidney donor pool.

Clinical validation of preoperative serum markers for liver fibrosis in living donor liver transplantation recipients.

To validate the reliability of fibrosis markers as predictors of graft survival in living donor liver transplantation (LDLT) recipients. We reviewed data retrospectively, from 163 patients who underwent adult LDLT with preoperative measurements of type IV collagen (CIV), Mac-2 binding protein glycosylation isomer (M2BPGi), and hyaluronic acid (HA). Patients were divided into high and low groups for each biomarker, based on optimal cutoff values, and graft loss within 6months was evaluated in each group. The high CIV level group showed significantly lower 6-month graft survival rates and significantly higher rates of postoperative sepsis and sepsis from pneumonia. However, the groups with high and low M2BPGi levels and those with high and low HA levels did not show significant differences in 6-month graft survival rates or rates of postoperative sepsis. Multivariate analysis revealed that a CIV level ≥ 590 was a significant predictor of graft loss within 6months, postoperative sepsis, and sepsis from pneumonia. Unlike other fibrosis markers, preoperative CIV levels can predict graft survival, postoperative sepsis, and sepsis from pneumonia after LDLT.

Short-term alcohol abstinence prior to liver transplantation and impact on rejection

Background & AimsAlcohol-associated liver disease (ALD) is a leading indication for liver transplant (LT). Historically, centers implemented 6-month abstinence periods prior to LT listing; however, the impact of this abstinence time on post-transplant rejection outcomes is unclear. This study evaluated if short-term abstinence is associated with increased rejection post-LT. MethodsThis single-center, retrospective, cohort included adult LT recipients from 11/1/2015 to 7/21/2021 with a primary indication of ALD. Patients were grouped by pre-transplant abstinence time of <6 or ≥6-months. The primary endpoint was biopsy proven acute rejection (BPAR) at 12-months post-LT. Secondary endpoints were infection, alcohol relapse, patient and graft survival at 12-months. ResultsOverall, 228 LT recipients met inclusion criteria (<6-months: n = 130; ≥6-months: n = 98). Patients with <6-months of abstinence were younger, had higher MELD scores, and more renal replacement therapy needs. Incidence of BPAR within 12 months of LT was 28 % in the <6-month group vs. 18 % in the ≥6-month group (p = 0.078). Tacrolimus initiation was lower at 7 days post-LT in the <6-month group (77% vs. 89 %; p = 0.029). Delay in tacrolimus initiation past 7 days post-LT was associated with greater BPAR (35% vs. 12 %; p = 0.0001). Increased bloodstream infections (21% vs. 7 %; p = 0.04) and CMV DNAemia (31% vs. 7 %; p = 0.0008) were seen in the <6-month group. Patient and graft survival was similar between groups. ConclusionsAbstinence time of <6-months was not associated with more BPAR within 12-months post-LT. The <6-month group was sicker at time of LT, which correlates to lower tacrolimus exposure early post-LT and heightened incidence of bacteremia and CMV viremia. Given the high acuity of the <6-month abstinence group, the risk of BPAR must be closely balanced with infection risk.

Efficacy and limitations of combined A2.CAR Treg and anti-CD154 therapy in a mouse model of haplo-mismatched heart transplantation.

The ability to induce allograft specific tolerance would reduce the need for daily pharmacological immunosuppression, improve post-transplant quality of life and transplant outcomes. Adoptive cell therapy with regulatory T cells expressing donor-specific Chimeric Antigen Receptors (CAR-Tregs) is a promising strategy, but monotherapy has not resulted in prolonged survival of grafts with multiple MHC mismatches. We used a clinically-relevant, haplo-mismatched model of heart transplantation in immune-competent C57BL/6 recipients to test the ability of HLA-A2-specific (A2) CAR Tregs to synergize with CD154 blockade to enhance graft survival. We found that in combination with a single low dose of anti-CD154, A2.CAR Tregs significantly prolonged heart allograft survival. Through use of grafts expressing the 2W-OVA transgene, tetramer tracking of 2W- and OVA-specific cells revealed that in mice with accepted grafts, the effects of A2.CAR Tregs included inhibition of endogenous donor-specific CD4 + and CD8 + T cell expansion, and B cell and antibody responses. Moreover, within the 2W-specific CD4 + T cell population, there was a significant increase in the proportion of FoxP3 pos cells, suggestive of infectious tolerance. In mice where CD154 blockade and A2.CAR Tregs failed to prolong graft survival, there was preferential expansion of FoxP3 neg A2.CAR T cells within the rejecting allograft. Thus, this study provides the first evidence for a synergistic effect between CAR Tregs and CD40-pathway blockade and supports the further refinement of this strategy as a promising future direction towards the goal of transplantation tolerance.

Incidence and risk factors for chronic rejection in pediatric liver transplantation.

Chronic rejection (CR) is a progressive immunological injury that frequently leads to long-term liver allograft dysfunction and loss. Although CR remains an important indication for retransplantation, as transplant immunosuppression has evolved, its prevalence in adults undergoing liver transplantation (LT) has declined. However, the incidence and factors that lead to CR in pediatric LT are poorly defined. Therefore, we sought to systematically measure CR's incidence and assess both the risk factors for developing CR and outcomes in a large cohort of pediatric recipients of LT. In this single-center study, we retrospectively analyzed and compared relevant recipient characteristics, surgical details, immunosuppression, graft, and patient survival in the CR and control groups over a 17-year period. After a median time of 1.9 years after LT, 19/356 recipients of LT (5.3%) developed CR in our cohort. Posttransplant lymphoproliferative disorder ( p = 0.01), infections ( p = 0.02), autoimmune liver diseases (HR = 7.3, p = <0.01), Black race (HR = 11.5, p = 0.01), and 2 or more episodes of T cell mediated rejection (HR = 5.1, p = <0.01) were associated with CR development. The retransplantation rate among CR cases was 15.8% at a median follow-up time of 4.1 years. Overall, patient survival was lower in the CR group (78.9%) versus controls (91.1%). While CR incidence in our pediatric cohort was lower than previously reported rates of >12%, the CR group had a higher graft failure rate that required retransplantation and lower overall patient survival. Thus, identifying risk factors may warrant specialized immunosuppression protocols and closer posttransplantation monitoring to reduce the risk of morbidity and mortality from CR.

Genitourinary malignancies in kidney transplant recipients.

Advances in immunosuppressive therapy and postoperative management have greatly improved the graft and patient survival rates after kidney transplantation; however, the incidence of post-transplant malignant tumors is increasing. Post-renal transplantation malignant tumors are associated with renal failure, immunosuppression, and viral infections. Moreover, the risk of developing cancer is higher in kidney transplant recipients than in the general population, and the tendency to develop cancer is affected by the background and environment of each patient. Recently, cancer after kidney transplantation has become the leading cause of death in Japan. Owing to the aggressive nature and poor prognosis of genitourinary malignancies, it is crucial to understand their epidemiology, risk factors, and best practices in kidney transplant recipients. This review has a special emphasis on the epidemiology, risk factors, and treatment protocols of genitourinary malignancies in kidney transplant recipients to enhance our understanding of the appropriate management strategies. Optimal immunosuppressive therapy and cancer management for these patients remain controversial, but adherence to the general guidelines is recommended.

Bridging the Gap: Advances and Challenges in Heart Regeneration from In Vitro to In Vivo Applications.

Cardiovascular diseases, particularly ischemic heart disease, area leading cause of morbidity and mortality worldwide. Myocardial infarction (MI) results in extensive cardiomyocyte loss, inflammation, extracellular matrix (ECM) degradation, fibrosis, and ultimately, adverse ventricular remodeling associated with impaired heart function. While heart transplantation is the only definitive treatment for end-stage heart failure, donor organ scarcity necessitates the development of alternative therapies. In such cases, methods to promote endogenous tissue regeneration by stimulating growth factor secretion and vascular formation alone are insufficient. Techniques for the creation and transplantation of viable tissues are therefore highly sought after. Approaches to cardiac regeneration range from stem cell injections to epicardial patches and interposition grafts. While numerous preclinical trials have demonstrated the positive effects of tissue transplantation on vasculogenesis and functional recovery, long-term graft survival in large animal models is rare. Adequate vascularization is essential for the survival of transplanted tissues, yet pre-formed microvasculature often fails to achieve sufficient engraftment. Recent studies report success in enhancing cell survival rates in vitro via tissue perfusion. However, the transition of these techniques to in vivo models remains challenging, especially in large animals. This review aims to highlight the evolution of cardiac patch and stem cell therapies for the treatment of cardiovascular disease, identify discrepancies between in vitro and in vivo studies, and discuss critical factors for establishing effective myocardial tissue regeneration in vivo.

Suppressive Role of Pigment Epithelium-derived Factor in a Rat Model of Corneal Allograft Rejection.

Immunological rejection is the most common reason for corneal transplantation failure. The importance of T cells in corneal allograft rejection is well demonstrated. Recent studies highlight that pigment epithelium-derived factor (PEDF) plays an immunoregulatory role in ocular diseases by enhancing the suppressive phenotype of regulatory T cells besides its other functions in neurotrophy and antiangiogenesis. The effects of PEDF on immune rejection were examined in rat models of corneal transplantation using slit-lamp microscope observation, immunohistochemistry, flow cytometry, and Western blot. In vitro, we demonstrated PEDF reduced alloreactive T-cell activation using real-time polymerase chain reaction, flow cytometry, and Western blot. Topical administration of PEDF provided corneal transplantation rats with an improved graft survival rate of corneal allografts, reduced hemangiogenesis, and infiltration of immune cells in corneas, in particular, type 17 T helper cells while increased regulatory T cells. Moreover, nerve reinnervation within grafts was promoted in PEDF-treated recipient rats. In vitro, PEDF inhibited alloreactive T-cell activation via the c-Jun N-terminal kinase/c-Jun signaling pathway and upregulated the expressions of interleukin-10 and transforming growth factor-β, emphasizing the suppressive role of PEDF on immune responses. Our results underscore the feasibility of PEDF in alleviating corneal allograft rejection and further illustrate its potential in managing immune-related diseases.

Living donors kidney transplantation and oxidative stress: Nitric oxide as a predictive marker of graft function.

Glomerular filtration rate is the best indicator of renal function and a predictor of graft and patient survival after kidney transplantation. In a single-centre prospective analysis, we assessed the predictive performances of 4 oxidative stress biomarkers in estimating graft function at 6 months and 1 year after kidney transplantation from living donors. Blood samples were achieved on days (D-1, D1, D2, D3, D6 and D8), months (M1, M3 and M6) and after one year (1Y). For donors, a blood sample was collected on D-1. Malondialdehyde (MDA), nitric oxide (NO), glutathione s-transferase (GST), myeloperoxydase (MPO), and creatinine (Cr) were measured by spectrophotometric essays. The estimated glomerular filtration rate by the modification of diet in renal disease equation (MDRD-eGFR) was used to assess renal function in 32 consecutive donor-recipient pairs. Pearson's and Spearman's correlations have been applied to filter out variables and covariables that can be used to build predictive models of graft function at six months and one year. The predictive performances of NO and MPO were tested by multivariable stepwise linear regression to estimate glomerular filtration rate at six months. Three models with the highest coefficients of determination stand out, combining the two variables nitric oxide at day 6 and an MDRD-eGFR variable at day 6 or MDRD-eGFR at day 21 or MDRD-eGFR at 3 months, associated for the first two models or not for the third model with donor age as a covariable (P = 0.000, r2 = 0.599, r2adj = 0.549; P = 0.000, r2 = 0.548, r2adj = 0.497; P = 0.000, r2 = 0.553, r2adj = 0.517 respectively). Quantification of nitric oxide at day six could be useful in predicting graft function at six months in association with donor age and the estimated glomerular filtration rate in recipient at day 6, day 21 and 3 months after transplantation.

Evolving Trends in the Management of Duodenal Leaks After Pancreas Transplantation: A Single-Centre Experience.

Duodenal leaks (DL) contribute to most graft losses following pancreas transplantation. However, there is a paucity of literature comparing graft preservation approach versus upfront graft pancreatectomy in these patients. We reviewed all pancreas transplants performed in our institution between 2000 and 2020 and identified the recipients developing DL to compare based on their management: percutaneous drainage vs. operative graft preservation vs. upfront pancreatectomy. Of the 595 patients undergoing pancreas transplantation, 74 (12.4%) developed a duodenal leak with a median follow up of 108months. Forty-five (61%) were managed by graft preservation strategies, with the rest being treated with upfront graft pancreatectomy. DL managed by graft preservation strategies had similar graft survival rates at 1 and 5-year compared to the matched cohort of population without DL (95% and 59% vs. 91% and 62%; p = 0.78). Multivariate analysis identified male recipient (OR: OR: 6.18; CI95%: 1.26-41.09; p = 0.04) to have higher odds of undergoing an upfront graft pancreatectomy. In appropriately selected recipients with DL, graft preservation strategies utilizing either interventional radiology guided percutaneous drainage or laparotomy with/without repair of leak can achieve comparable long-term graft survival rates compared to recipients without DL.

Secondary Glaucoma Following Corneal Transplantation: A Comprehensive Review of Pathophysiology and Therapeutic Approaches.

Corneal transplantation is a critical surgical procedure aimed at restoring vision in patients with corneal blindness or severe damage. This review focuses on secondary glaucoma, a significant postoperative complication, with the primary objective of providing a comprehensive analysis of its pathophysiology, risk factors, diagnostic challenges, and therapeutic approaches. Unlike other reviews, this work emphasizes the interplay between inflammatory responses, corticosteroid use, and structural changes in the eye that lead to elevated intraocular pressure (IOP) after transplantation. A comprehensive review of the literature was conducted, including studies on postcorneal transplantation glaucoma, to highlight both clinical outcomes and the efficacy of current management strategies. Key findings indicate that medical treatments, such as prostaglandin analogs and beta-blockers, are effective for IOP control in the early stages, while surgical interventions, like trabeculectomy, are often necessary for more advanced cases. Diagnostic challenges, such as the difficulty of accurate IOP measurement posttransplant, are underscored, along with the importance of advanced imaging techniques for the early detection of optic nerve damage. The pathophysiology of secondary glaucoma involves a complex interaction of postsurgical inflammation, steroid-induced complications, and anatomical changes that hinder aqueous humor outflow. Diagnosis requires a combination of tonometry, gonioscopy, and imaging technologies. Management strategies range from pharmacological treatments to surgical options, with a critical focus on balancing IOP control and minimizing risks to graft survival. Clinically, these findings highlight the need for proactive and tailored management of IOP in corneal transplant patients to preserve both graft function and long-term visual outcomes. Future research should focus on improving diagnostic accuracy, developing less invasive surgical techniques, and exploring personalized medicine approaches, including genetic profiling and targeted therapies.