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Survival and functionality of xeno-free human embryonic stem cell-derived retinal pigment epithelial cells on polyester substrate after transplantation in rabbits
摘要： Purpose: To study immunogenic properties of human embryonic stem cell–derived retinal pigment epithelium (hESC-RPE) and to evaluate subretinal xenotransplantation of hESC-RPE on porous polyethylene terephthalate (PET) in rabbits. Methods: Human ESC-RPE cells were characterized by morphology, transepithelial electrical resistance (TER), protein expression and photoreceptor outer segment phagocytosis in vitro. Expression of major histocompatibility complex (MHC) proteins was assessed in conventionally or xeno-free produced hESC-RPE with interferon-gamma (IFN-γ) stimulation (n = 1). Xeno-free hESC-RPE on PET with TER < 200 Ω·cm2 or PET alone were transplanted into 18 rabbits with short-term triamcinolone with extended tacrolimus immunosuppression. Rabbits were monitored by spectral domain optical coherence tomography. After 4 weeks, the eyes were processed for histology and transmission electron microscopy. Results: Upon in vitro IFN-γ stimulation, xeno-free hESC-RPE expressed lower level of MHC-II proteins compared to the conventional cells. Outer nuclear layer (ONL) atrophy was observed over the graft in most cases 4 weeks post-transplantation. In 3/4 animals with high TER hESC-RPE, but only in 1/3 animals with low TER hESC-RPE, ONL atrophy was observed already within 1 week. Retinal cell infiltrations were more frequent in animals with high TER hESC-RPE. However, the difference was not statistically significant. In three animals, preservation of ONL was observed. Weekly intravitreal tacrolimus did not affect ONL preservation. In all animals, hESC-RPE cells survived for 4 weeks, but without tacrolimus, enlarged vacuoles accumulated in hESC-RPE (n = 1). Conclusions: Xenografted xeno-free hESC-RPE monolayers can survive and retain some functionality for 4 weeks following short-term immunosuppression. The preliminary findings of this study suggest that further investigations to improve transplantation success of hESC-RPE xenografts in rabbits should be addressed especially toward the roles of hESC-RPE maturation stage and extended intravitreal immunosuppression.
关键词： xeno-free,age-related macular degeneration,cell therapy,RPE transplantation,pluripotent stem cell
更新于2025-09-23 15:23:52
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Indocyanine green fluorescence image-guided total laparoscopic living donor right hepatectomy: The first case report from Mainland China
摘要： INTRODUCTION: Total laparoscopic living donor right hepatectomy (TLDRH) is sporadically reported worldwide. Liver transection margin used to be determined by ischemic demarcation or intraoperative ultrasonography. To identify the site of bile duct division relied on preoperative MRCP and intraoperative cholangiography, which is experience demanding. PRESENTATION OF CASE: A 34-year-old man volunteered for living donation to his brother who suffered decompensated HBV-related cirrhosis. Right lobe donation without MHV fulfilled the volumetric criteria. After hilum dissection, ICG was injected into the right portal branch. Right lobe was transected tracing the real-time fluorescence-enhanced borderline and the course of MHV. The right bile duct was transected above the bifurcation that was fluorescently visualized within the parenchyma. The liver graft was retrieved from a pre-made suprapubic incision after simple vascular clamping. The warm ischemia time was 6 min. The recipient procedure was successful with back-table graft venoplasty using cryopreserved iliac artery allografts. The donor recovered uneventfully and was discharged from hospital on POD 7. DISCUSSION: The operative time, blood loss and postoperative course of donor is comparable to those undergoing ordinary laparoscopic right hepatectomy in our institute. ICG fluorescence can real-timely visualize the surgical margin and biliary branches of right lobe, which helps preserve every last bit of functional liver volume for the donor and avoid the complicated traditional intraoperative cholangiography. CONCLUSION: TLDRH proves to be achievable in surgical teams confortable with both laparoscopic hepatectomy and LDLT. ICG fluorescence navigation could make the procedure simplified, safer and more accurate. More practice and technical modification are necessary.
关键词： Fluorescence,Laparoscopy,Indocyanine green,Right hepatectomy,Living donor liver transplantation
更新于2025-09-23 15:22:29
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Monitoring neovascularization and integration of decellularized human scaffolds using photoacoustic imaging
摘要： Tissue engineering is a branch of regenerative medicine that aims to manipulate cells and scaffolds to create bioartificial tissues and organs for patients. A major challenge lies in monitoring the blood supply to the new tissue following transplantation: the integration and neovascularization of scaffolds in vivo is critical to their functionality. Photoacoustic imaging (PAI) is a laser-generated ultrasound-based technique that is particularly well suited to visualising the microvasculature due to the high optical absorption of haemoglobin. Here, we describe an early proof-of-concept study in which PAI in widefield tomography mode is used to image biological, decellularized human tracheal scaffolds. We found that photoacoustic imaging allowed the longitudinal tracking of scaffold integration into subcutaneous murine tissue with high spatial resolution at depth over an extended period of time. The results of the study were consistent with post-imaging histological analyses, demonstrating that photoacoustic imaging can be used to non-invasively monitor the extent of vascularization in biological tissue-engineered scaffolds. We anticipate that this technique could find application in tissue-engineering studies aimed at improving the speed and extent of scaffold neovascularization. With technological development, it could also be used to inform the clinical timing of surgical procedures following heterotopic transplantation to establish vasculature.
关键词： vascularization,angiogenesis,photoacoustic imaging,transplantation,tissue engineering,trachea
更新于2025-09-23 15:22:29
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Quantitative assessment of microperfusion by indocyanine green angiography in kidney transplantation resembles chronic morphological changes in kidney specimens
摘要： Indocyanine green fluorescence angiography enables a quantitative real-time perfusion assessment in kidney transplantation. The results of intraoperative microperfusion of the kidney allograft were compared to the renal chronicity score in pre-transplantation kidney biopsy specimens. The intrarenal resistance index was calculated by duplex sonography as a method of reference. Seventy-seven patients with end stage renal disease undergoing kidney transplantation were prospectively included in two centers. Correlation analysis of chronic changes in kidney biopsy specimens and the ingress of ICG fluorescence signal were investigated. The results yielded a significantly negative correlation for the renal chronicity (r= -0.294, p=0.017) as well as the intestinal fibrosis and tubular atrophy score (r=-0.328, p=0.007). There was a significant inverse relationship between the ingress and the mean RI values of the upper pole of the kidney. In summary, fluorescence angiography reflects preexisting morphological changes of the renal cortex. ICG angiography may serve as an alternative method for the assessment of microperfusion of the allograft.
关键词： kidney transplantation,indocyanine green,kidney specimen,graft perfusion
更新于2025-09-23 15:22:29
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Favorable impact of extracorporeal photopheresis in acute and chronic graft versus host disease: Prospective single-center study
摘要： Background: Graft vs host disease (GVHD) is the most severe complication of allogeneic hematopoietic cell transplantation. Conventional immunosuppressive therapy increases morbidity and mortality without improving survival. Extracorporeal photopheresis (ECP) has been introduced as an alternative treatment in steroid-dependent and steroid-refractory disease. Study design and methods: We studied the safety and efficacy of ECP as a second- or third-line treatment in GVHD. Results: ECP was administered in 21 patients with grade III-IV acute GVHD and 88 patients with extensive chronic GVHD, without ECP-related adverse events. Eight patients receiving four or less ECP sessions were not further analyzed. The majority of acute GVHD patients (84%) presented partial (15) or complete (1) response to ECP. Immunosuppression was reduced in 10 of 19 patients and ceased in 1 of 19 patients. One-year cumulative incidence (CI) of transplant-related mortality (TRM) (17.6%) was associated with the lack of response to ECP and steroid refractoriness. With a follow-up of 17.5 (1.8-58.3) months, 1-year overall survival (OS) (52.5%) was independently associated with a higher number of ECP sessions. Regarding chronic GVHD, complete response was achieved in 35 patients, whereas partial response in 25 patients, leading to an overall response rate of 73%. Cutaneous sclerosis manifestations were associated with higher response rates. With a follow-up of 68.1 (5.4-283.1) months, 5-year CI of TRM (24.1%) was associated only with a number of ECP sessions. The 5-year OS (64.5%) was independently associated with number of ECP sessions and cutaneous manifestations. Conclusion: Our findings suggest that ECP is safe and effective for GVHD and should be considered early in the course of GVHD, before irreversible end-organ damage has been established.
关键词： hematopoietic stem cell transplantation,graft vs host-disease,extracorporeal photopheresis,allogeneic
更新于2025-09-23 15:21:01
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Predictive Value of Corneal Donor Demographics on Endothelial Cell Density
摘要： Corneal endothelial cell density (ECD) is an important measure for determining suitability for transplantation. Although age has been correlated with ECD, the impact of sex and ethnicity is unclear. Methods: Corneal donor information from SightLife Eye Bank was collected between 2012 and 2016. Tests of association were adjusted for covariates using linear regression including age, race, and sex. “Unsuitable for transplantation” was a label assigned to specimens with extensive cell dropout, ECD ,2000 cells/mm2, and poor cell morphology. Repeated-measures analysis was used to account for the within-individual correlation between left and right eyes. Results: A total of 39,679 donor corneas were analyzed, with a mean ECD 2743.5 cells/mm2 and mean age of 58. Simple linear regression demonstrated an association between ECD and age (P , 0.001). Multiple regression showed no association between sex and ECD. Compared with whites, African American, and Asian ethnicities were predictors of increased ECD (mean +45.7 cells/mm2 (P , 0.001) and +90.3 cells/mm2 (P , 0.001), respectively); Hispanic ethnicity was a predictor of decreased ECD [mean 236.9 cells/mm2 (P = 0.002)]. A total of 233 (0.59%) corneas were unsuitable for transplantation, which was associated with age (P , 0.001) but not sex or ethnicity. Conclusions: Analysis of a large sample of donor corneas continues to show age but not sex as a predictor of decreased ECD. African American and Asian ethnicities tend to have slightly higher ECD than that of white donors, whereas Hispanic donors have slightly lower ECD; however, ethnicity was not a predictor of suitability for transplantation. Clinical signi?cance of these ?ndings is yet to be determined.
关键词： corneal endothelium,corneal transplantation,corneal donor characteristics
更新于2025-09-11 14:15:04
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Medium- to long-term survival and functional examination of human iPSC-derived retinas in rat and primate models of retinal degeneration
摘要： Background: We have previously reported that xeno-transplanted human ESC-derived retinas are able to mature in the immunodeficient retinal degeneration rodent models, similar to allo-transplantations using mouse iPSC-derived retina. The photoreceptors in the latter developed outer segments and formed synapses with host bipolar cells, driving light responses of host retinal ganglion cells. In view of clinical application, here we further confirmed the competency of human iPSC-derived retina (hiPSC-retina) to mature in the degenerated retinas of rat and monkey models. Methods: Human iPSC-retinas were transplanted in rhodopsin mutant SD-Foxn1 Tg(S334ter)3LavRrrc nude rats and two monkeys with laser-induced photoreceptor degeneration. Graft maturation was studied by immunohistochemistry and its function was examined by multi-electrode array (MEA) recording in rat retinas and visually-guided saccade (VGS) in a monkey. Findings: A substantial amount of mature photoreceptors in hiPSC-retina graft survived well in the host retinas for at least 5 months (rat) to over 2 years (monkey). In 4 of 7 transplanted rat retinas, RGC light responses were detected at the grafted area. A mild recovery of light perception was also suggested by the VGS performance 1.5 years after transplantation in that monkey. Interpretation: Our results support the competency of hiPSC-derived retinas to be clinically applied for transplantation therapy in retinal degeneration, although the light responses observed in the present models were not conclusively distinguishable from residual functions of degenerating host retinas. The functional analysis may be further elaborated using other models with more advanced retinal degeneration.
关键词： Human iPSC,Retinal degeneration,Photoreceptor transplantation,Visually-guided saccades,Multi-electrode array
更新于2025-09-04 15:30:14
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Nanoparticle-Based Imaging of Clinical Transplant Populations Encapsulated in Protective Polymer Matrices
摘要： A recent clinical trial proves that autologous olfactory mucosal cell (OMC) transplantation improves locomotion in dogs with naturally occurring spinal injuries comparable to human lesions. However, not all dogs respond to the treatment, likely due to the transplantation procedures involving injections of cell suspensions that are associated with cell death, uneven cell distribution, and cell washout. Encapsulating cells in protective hydrogel matrices offers a tissue engineering solution to safely achieve 3D growth of viable transplant cells for implantation into injury sites, to improve regenerative outcomes. It is shown for the first time that canine OMCs (cOMCs) can be propagated with high viability in 3D collagen matrices. Further, a method to incorporate cOMCs pre-labeled with clinical-grade iron oxide nanoparticles into the constructs is described. Intraconstruct labeled cells are visualized using magnetic resonance imaging, offering substantial promise for in vivo tracking of cOMCs delivered in protective matrices.
关键词： magnetic nanoparticle,canine olfactory mucosal cell,cell transplantation,hydrogel,spinal injury
更新于2025-09-04 15:30:14
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<i>In vitro</i> and <i>in vivo</i> Proteomic Comparison of Human Neural Progenitor Cell-Induced Photoreceptor Survival
摘要： Retinal degenerative diseases are some of the leading causes of blindness with few treatments. Various cell-based therapies have aimed to slow the progression of vision loss by preserving light-sensing photoreceptor cells. A subretinal injection of human neural progenitor cells (hNPCs) into the Royal College of Surgeons (RCS) rat model of retinal degeneration has aided in photoreceptor survival, though the mechanisms are mainly unknown. Identifying the retinal proteomic changes that occur following hNPC treatment will lead to better understanding of neuroprotection. To mimic the retinal environment following hNPC injection, a co-culture system of retinas and hNPCs was developed. Less cell death occurred in RCS retinal tissue co-cultured with hNPCs than in retinas cultured alone, suggesting that hNPCs provide retinal protection in vitro. Comparison of ex vivo and in vivo retinas identified NRF2-mediated oxidative response signaling as an hNPC-induced pathway. This is the first study to compare proteomic changes following treatment with hNPCs in both an ex vivo and in vivo environment, further allowing the use of ex vivo modeling for mechanisms of retinal preservation. Elucidation of the protein changes in the retina following hNPC treatment may lead to the discovery of mechanisms of photoreceptor survival and its therapeutic for clinical applications.
关键词： retinal degeneration,stem cells,transplantation,Human neural progenitor cells,neuroprotection
更新于2025-09-04 15:30:14
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ST Elevation Infarction after Heart Transplantation Induced by Coronary Spasms and Mural Thrombus Detected by Optical Coherence Tomography
摘要： The case illustrates the possible link between coronary spasms, intraluminal thrombus formation, and widespread organized and layered thrombi in HTx patients. Furthermore, the case underlines the clinical value of OCT as a novel method for high-resolution vessel imaging in heart-transplanted (HTx) patients with coronary spasms and suspected coronary artery disease. Coronary spasms and sudden death are frequent complications after HTx. The underlying mechanisms leading to these complications are unknown. The present case displays the clinical course of a 19-year-old HTx patient who was hospitalized due to acute myocardial infarction induced by severe coronary spasms. The patients remained unstable on conservative therapy. Therefore, an optical coherence tomography (OCT) was performed and revealed massive, organized thrombi in the left main coronary artery, the circumflex coronary artery, and the left anterior descending coronary artery. The patient was stabilized after percutaneous coronary intervention. As a mural thrombus often goes undetected by coronary angiography, OCT may prove beneficial in HTx patients with myocardial infarction or suspected coronary spasms.
关键词： myocardial infarction,coronary spasms,optical coherence tomography,heart transplantation,mural thrombus
更新于2025-09-04 15:30:14