The Impact of Blood Transfusion on the Efficiency of Stem Cell Transplants

Background: While blood product transfusion is essential for managing hematologic deficits in Allogenic Hematopoietic stem cell transplant (AHSCT) recipients, it has risks including infectious disease transmission, alloimmunization, and transfusion reactions. These risks have sparked an ongoing debate regarding the overall impact of transfusions on patient outcomes. Thus, this study aimed to evaluate the impact of Red Blood Cells (RBCs) and/or platelet transfusion on the infection incidence and overall survival in AHSCT patients. Methods: We performed a retrospective analysis of clinical and laboratory data of sixty adult patients with primary malignant hematological disorder who had undergone AHSCT. Participants’ data were categorized into two groups;Group 1 (low transfusion group) consisted of patients receiving 10 units. Quantitative data were expressed as mean ± SD. The t-test of significance and Chi-square (χ2) test were used, with p ≤ 0.05 considered significant. Result: A total of 60 patients’ data was included. In Group 1, out of 30 patients, 13 (43.33%) developed infections. In contrast, Group 2 had 21 (70%) out of 30 patients develop infections. Group 1 had a higher survival rate (57.8%) than Group 2 (transfusion > 10 units) (46.2%) with a chi-square value = 23.56, and p-value Conclusion: The volume of blood product transfusions has a considerable impact on patient outcomes, particularly infection and survival rates. Additional long-term prospective studies and larger randomized controlled trials are needed to strengthen the evidence for determining transfusion protocols for these patients.

Over thousand liver transplants performed at a liver transplant center in China

Recently the Liver Transplantation Center of the First Affiliated Hospital,Zhejiang University School of Medicine announced the successful performance of 1021 liver transplants by October 17,2011.At a gathering celebrating this event,experts from the USA and China highly appreciated this achievement made

Recent experience of 70 pediatric living donor liver transplants(LDLTs): arterial reconstruction

Objective:Hepatic artery thrombosis(HAT)is a serious complication after liver transplantation(LT).We present recent living donor liver transplant(LDLT)results from our center,focusing on hepatic artery reconstruction and complications.Methods:From July 2011 to July 2018,98 pediatric(<18years)LTs were performed at our center(70 LDLT/28 cadaveric grafts).

Glypican 4 down-regulation in pluripotent stem cells as a potential strategy to improve differentiation and to impair tumorigenicity of cell transplants

Recent advances in stem cell technologies have opened new avenues for the treatment of a number of diseases still lacking effective therapeutic options.Cell transplantation has emerged as among the most promising clinical intervention for disorders such as injuries,diabetes,liver diseases, neurodegeneration and heart failure （Lee et al., 2013; Forbes and Rosenthal, 2014; Tabar and Studer, 2014）.

Field Establishment of Cashew （Anacardium occidentale L,） Transplants as Affected by Nursery Periods

Field establishment of cashew has been seriously hampered by long delay in the nursery. This has led to transplanting of overgrown seedlings resulting in high transplant mortality, especially during the first dry season on the field. The experiment was set up to study field establishment of cashew transplants as affected by the nursery periods. Four nursery periods were tried. These were cashew transplanted at 3, 4, 8 and 12 weeks after sowing （WAS）. The experiment was laid out in randomized complete block with three replicates. Records were taken on morphological parameters and survival percentage of the transplants till fruiting. Cashew seedlings transplanted at 12 WAS had better morphological plant parameters compared to other transplants. At 3 months after transplanting （MAT）, cashew transplants of 12 WAS were 172.6%, 93.7% and 38.5% taller than transplants of 3, 4 and 8 WAS, respectively and the differences were significant （P 〈 0.05）. Similarly, seedlings transplanted at 12 WAS had 245.4%, ! 51.9% and 99.4% more leaves than those of 3, 4 and 8 WAS at 3 MAT, respectively. However, the survival percent of cashew seedlings transplanted at 12 WAS were 66.7% followed by that of 3 WAS with 75.0% within 12 MAT. No transplant mortality was incurred in seedlings transplanted at 4 and 8 WAS up to 12 MAT. For optimum growth and high survival rate, transplanting cashew seedlings between 4 and 8 WAS will be encouraged so as to have high plant stands, thereby, reducing supply in the following planting season.

Chemokine Receptors CCR1, CCR3, CCR7 and Chemokines CX3CL1 and CCL5 are Significantly Up-Regulated and Very Reliable for Acute Rejection Diagnosis of Kidney Transplants

Background: The allo-immune response following organ transplantation constitutes one of the main determinants concerning both short- and long- term outcomes in renal graft recipients. Chemokines and their receptors play a diversified and important role, either homeostatic or inflammatory and direct different immune-competent cell types to the allograft. While deeply studied in the last two decades, controversy persists as a result of chemokines’ pleiotropic actions. We report our analysis of CCR1, CCR3, CCR7, CCL5 and CX3CL1 expression or synthesis by graft-infiltrating cells in human kidney transplants (KTx). At the same time, we tested their robustness in diagnosing acute rejection. Methods: Fine-needle aspiration biopsies (Fnab) were performed either on days 7 or 14 post-transplantation among stable KTx and on the day of acute rejection (AR) diagnosis. Fnab cytopreparations were studied by the enzymatic avidin-biotin complex staining for CCR1, CCR3, CCR7 and CX3CL1. From another subgroup of cases, Fnab samples were cultured for 48 hours and the supernatants were analysed for CCL5 by ELISA. Results: The group of AR cases showed a significantly up-regulated expression of CCR1, CCR3, CCR7 and CX3CL1 and a significantly higher synthesis of CCL5. The positive predictive values were respectively 92%, 97%, 85%, 76% and 78% and negative predictive values were by the same order, 100%, 73%, 100%, 98% and 83%. Conclusions: Our study permits us to advance that CCR1 and CCR3 play a significant and non-redundant role in acute rejection, and it is the first report of CCR3 association with rejection, probably related to CCL5. The presence inside the graft of significant up-regulation for CCR7 surmises that part of antigen presentation may be performed there without being restricted to secondary lymphoid sites. Our results with CX3CL1 confirm other reports.

Steps To ward HIV Cure Two more HIV-infected patients appear to be virus-free after bone-marrow transplants

THIS year＇s International AIDS Society Conference on HIV Pathogenesis, Treatment and Preven-／tion, held in Kuala Lumpur, Malaysia, made major headlines when Timothy Hendch, an American doctor, announced that two more cancer patients may have been cured of HIV after receiving bone-marrow transplants to treat lymphoma. Both patients had been taking retroviral medication, and continued to do so after the transplants as their viral levels sank until doctors were unable to find any traces of HIV in the patients＇ blood.

ABO incompatible renal transplants:Good or bad?

ABO incompatible kidney transplantation(ABOi-KT) was previously considered to be an absolute contraindication for patients with end-stage kidney disease(ESKD) due to hyperacute rejection related to blood type barrier. Since the first successful series of ABOi-KT was reported, ABOi-KT is performed increasingly all over the world. ABOi-KT has led to an expanded donor pool and reduced the number of patients with ESKD awaiting deceased kidney transplantation(KT). Intensified immunosuppression and immunological understanding has helped to shape current desensitization protocols. Consequently, in recent years, ABOi-KT outcome is comparable to ABO compatible KT(ABOc-KT). However, many questions still remain unanswered. In ABOi-KT, there is an additional residual immunological risk that maylead to allograft damage, despite using current diverse but usually intensified immunosuppressive protocols at the expense of increasing risk of infection and possibly malignancy. Notably, in ABOi-KT, desensitization and antibody reduction therapies have increased the cost of KT. Reassuringly, there has been an evolution in ABOiKT leading to a simplification of protocols over the last decade. This review provides an overview of the history, outcome, protocol, advantages and disadvantages in ABOi-KT, and focuses on whether ABOi-KT should be recommended as a therapeutic option of KT in the future.

BK nephropathy in the native kidneys of patients with organ transplants: Clinical spectrum of BK infection

Nephropathy secondary to BK virus, a member of the Papoviridae family of viruses, has been recognized for some time as an important cause of allograft dysfunction in renal transplant recipients. In recent times, BK nephropathy(BKN) of the native kidneys has being increasingly recognized as a cause of chronic kidney disease in patients with solid organ transplants, bone marrow transplants and in patients with other clinical entities associated with immunosuppression. In such patients renal dysfunction is often attributed to other factors including nephrotoxicity of medications used to prevent rejection of the transplanted organs. Renal biopsy is required for the diagnosis of BKN. Quantitation of the BK viral load in blood and urine are surrogate diagnostic methods. The treatment of BKN is based on reduction of the immunosuppressive medications. Several compounds have shown antiviral activity, but have not consistently shown to have beneficial effects in BKN. In addition to BKN, BK viral infection can cause severe urinary bladder cystitis, ureteritis and urinary tract obstruction as well as manifestations in other organ systems including the central nervous system, the respiratory system, the gastrointestinal system and the hematopoietic system. BK viral infection has also been implicated in tumorigenesis. The spectrum of clinical manifestations from BK infection and infection from other members of the Papoviridae family is widening. Prevention and treatment of BK infection and infections from other Papovaviruses are subjects of intense research.

Single vs dual(en bloc) kidney transplants from donors ≤ 5 years of age: A single center experience

AIM: To compare outcomes between single and dual en bloc(EB) kidney transplants(KT) from small pediatric donors. METHODS: Monocentric nonprospective review of KTs from pediatric donors ≤ 5 years of age. Dual EB KT was defined as keeping both donor kidneys attached tothe inferior vena cava and aorta, which were then used as venous and arterial conduits for the subsequent transplant into a single recipient. Donor age was less useful than either donor weight or kidney size in decision-making for kidney utilization as kidneys from donors < 8 kg or kidneys < 6 cm in length were not transplanted. Post-transplant management strategies were standardized in all patients.RESULTS: From 2002-2015, 59 KTs were performed including 34 dual EB and 25 single KTs. Mean age of donors(17 mo vs 38 mo, P < 0.001), mean weight(11.0 kg vs 17.4 kg, P = 0.046) and male donors(50% vs 84%, P = 0.01) were lower in the dual EB compared to the single KT group, respectively. Mean cold ischemia time(21 h), kidney donor profile index(KDPI; 73% vs 62%) and levels of serum creatinine(SCr, 0.37 mg/d L vs 0.49 mg/d L, all P = NS) were comparable in the dual EB and single KT groups, respectively. Actuarial graft and patient survival rates at 5-years follow-up were comparable. There was one case of thrombosis resulting in graft loss in each group. Delayed graft function incidence(12% dual EB vs 20% single KT, P = NS) was slightly lower in dual EB KT recipients. Initial duration of hospital stay(mean 5.4 d vs 5.6 d) and the one-year incidences of acute rejection(6% vs 16%), operative complications(3% vs 4%), and major infection were comparable in the dual EB and single KT groups, respectively(all P = NS). Mean 12 mo SCr and abbreviated MDRD levels were 1.17 mg/d L vs 1.35 mg/d L and 72.5 m L/min per 1.73 m^2 vs 60.5 m L/min per 1.73 m^2(both P = NS) in the dual EB and single KT groups, respectively. CONCLUSION: By transplanting kidneys from young pediatric donors into adult recipients, one can effectively expand the limited donor pool and achieve excellent medium-term outcomes.

Significance of progressive liver fibrosis in pediatric liver transplants: A review of current evidence

This article reviews the current evidence and knowledge of progressive liver fibrosis after pediatric liver transplantation.This often-silent histologic finding is common in long-term survivors and may lead to allograft dysfunction in advanced stages.Surveillance through protocolized liver allograft biopsy remains the gold standard for diagnosis,and recent evidence suggests that chronic inflammation precedes fibrosis.

Renal transplants from older deceased donors: Is preimplantation biopsy useful? A monocentric observational clinical study

AIM To compare survival of kidney transplants from deceased extended criteria donors(ECD) according to:(1) donor graft histological score; and(2) allocation of high score grafts either to single(SKT) or dual(DKT) transplant.METHODS Renal biopsy was performed as part of either a newly adopted DKT protocol, or of surveillance protocol in the past. A total 185 ECD graft recipients were categorized according to pre-implantation graft biopsy into 3 groups: SKT with graft score 1 to 4 [SKT(1-4), n = 102]; SKT with donor graft score 5 to 8 [SKT(> 4), n = 30]; DKT with donor graft score 5 to 7(DKT, n = 53). Graft and patient survival were analyzed by Kaplan-Meier curves and compared by log-rank test. Mean number of functioning graft years by transplant reference, and mean number of dialysis-free life years by donor reference in recipients were also calculated at 1, 3 and 6 years from transplantation. RESULTS There were no statistically significant differences in graft and patient survival between SKT(1-4) and SKT(> 4), and between SKT(> 4) and DKT. Recipient renal function(plasma creatinine and creatinine clearance) at 1 years did not differ in SKT(1-4) and SKT(> 4)(plasma creatinine 1.71 ± 0.69 and 1.69 ± 0.63 mg/dL; creatinine clearance 49.6 + 18.5 and 52.6 + 18.8 m L/min, respectively); DKT showed statistically lower plasma creatinine(1.46 ± 0.57, P < 0.04) but not different creatinine clearance(55.4 + 20.4). Due to older donor age in the DKT group, comparisons were repeated in transplants from donors older than 70 years, and equal graft and patient survival in SKT and DKT were confirmed. Total mean number of functioning graft years by transplant reference at 1, 3 and 6 post-transplant years were equal between the groups, but mean number of dialysis-free life years by donor reference were significantly higher in SKT(mean difference compared to DKT at 6 years: 292 [IQR 260-318] years/100 donors in SKT(1-4) and 292.5 [(IQR 247.8-331.6) in SKT(> 4)]. CONCLUSION In transplants from clinically suitable ECD donors, graft survival was similar irrespective of pre-implantation biopsy score and of allocation to SKT or DKT. These results suggest use of caution in the use of histology as the only decision criteria for ECD organ allocation.

Eliminating viral hepatitis in children after liver transplants:How to reach the goal by 2030

Viral hepatitis infections are a great burden in children who have received liver transplant.Hepatotropic viruses can cause liver inflammation that can develop into liver graft fibrosis and cirrhosis over the long term.Immunological reactions due to viral hepatitis infections are associated with or can mimic graft rejection,rendering the condition difficult to manage.Prevention strategies using vaccinations are agreeable to patients,safe,cost-effective and practical.Hence,strategies to eliminate viral hepatitis A and B focus mainly on immunization programmes for children who have received a liver transplant.Although a vaccine has been developed to prevent hepatitis C and E viruses,its use is not licensed worldwide.Consequently,eliminating hepatitis C and E viruses mainly involves early detection in children with suspected cases and effective treatment with antiviral therapy.Good hygiene and sanitation are also important to prevent hepatitis A and E infections.Donor blood products and liver grafts should be screened for hepatitis B,C and E in children who are undergoing liver transplantation.Future research on early detection of viral hepatitis infections should include molecular techniques for detecting hepatitis B and E.Moreover,novel antiviral drugs for eradicating viral hepatitis that are highly effective and safe are needed for children who have undergone liver transplantation.

Differentiation and functional connectivity of fetal tectal transplants

Data from studies analyzing the differentiation and functional connectivity of embryo nic neural tissue grafted into the mammalian nervous system has led to the clinical testing of the fetal graft approach in patients with neurodegenerative disease.While some success has been achieved,ethical concerns have led to a search for alternative therapeutic strategies,mostly exploring the use of neural precursors or neurons derived from pluripotent stem cells to replace damaged host neurons and restore lost circuitries.These more recent studies address questions of graft viability,differentiation,and connectivity similar to those posed by researchers in earlier fetal transplant work,thus reviews of the fetal graft literature may inform and help guide ongoing research in the stem cell/organoid field.This brief review describes some key observations from research into the transplantation of neural tissue into the rat visual syste m,focusing on grafts of the fetal supe rior colliculus(tectal grafts) into neonatal or adult hosts.In neonate hosts,grafts quickly develop connections with the underlying host mid b rain and attain a morphology typical of mature grafts by about 2 weeks.G rafts consistently contain numerous localized regions which,based on neurofibrillar staining,neuronal morphology(Golgi),neurochemistry,receptor expression,and glial architecture,are homologous to the stratum griseum supe rficiale of normal superior colliculus.These localized "patches" are also seen after explant culture and when donor tectal tissue is dissociated and reaggregated prior to transplantation.In almost all circumstances,host retinal innervation is restricted to these localized patches,but only those that are located adjacent to the graft surfa ce.Synapses are formed and there is evidence of functional drive.The only exception occurs when Schwann cells are added to dissociated tecta prior to reaggregation.In these co-grafts,the peripheral glia appear to compete with local target fa ctors and host retinal ingrowth is more widespread.Other afferent systems(e.g.,host co rtex,serotonin) show different patterns of innervation.The host cortical input originates more from extrastriate regions and establishes functional excitato ry synapses with grafted neurons.Finally,when grafted into optic tra ct lesions in adult rat hosts,spontaneously regrowing host retinal axons retain the capacity to selectively innervate the localized patches in embryonic tectal grafts,showing that the specific affinities between adult retinal axons and their targets are not lost during regeneration.While the research described here provides some pertinent information about development and plasticity in visual pathways,a more general aim is to highlight how the review of the extensive fetal graft lite rature may aid in an appreciation of the positive(and negative) fa ctors that influence survival,differentiation,connectivity and functionality of engineered cells and organoids transplanted into the central nervous system.

NEOPLASTIC CELL APOPTOSIS IN NUDE MICE TRANSPLANTS WITH NASOPHARYNGEAL CARCINOMA CELL LINES

Objective: To observe the morphological features of neoplastic cell apoptosis developed in nude mice transplants with nasopharyngeal carcinoma (NPC) cell lines, CNE-1 and CNE-2, and to investigate the roles of p53, bcl-2 and bax playing in the process of apoptosis. Methods: CNE-1 and CNE-2 cell lines were inoculated and passed in nude mice for 3 generations. The cell apoptosis was detected on H & E and TUNEL staining slides. The expression of p53, bcl-2 and bax were detected by using immunohistochemistry. p53 gene alteration was assayed in cell lines and transplants by PCR-SSCP. Results: A considerable number of neoplastic cells underwent apoptosis in CNE-1 and CNE-2 transplant tissues. The “shrinkage necrosis” and apoptotic bodies were the main appearances of apoptosis. The p53 alteration was detected in exon 8 by PCR-SSCP and p53 protein accumulation observed in the cell smears and nude mice transplant tissue sections. All the transplant tissue sections of 3 passages showed bcl-2 negativity and bax overexpression. Conclusion: The neoplastic cells of CNE-1 and CNE-2 transplants underwent death mainly taking the way of apoptosis. The “shrinkage necrosis” and apoptotic bodies were the main morphological features of apoptosis seen in those transplants. The apoptosis in CNE-1 or CNE-2 nude mice transplant is highly probable through a p53-independent and bax-mediated pathway.

Mortality assessment for pancreas transplants in the United States over the decade 2008-2018

BACKGROUND Pancreas transplant is the only treatment that establishes normal glucose levels for patients diagnosed with diabetes.However,since 2005,no comprehensive analysis has compared survival outcomes of:(1)Simultaneous pancreas-kidney(SPK)transplant;(2)Pancreas after kidney(PAK)transplant;and(3)Pancreas transplant alone(PTA)to waitlist survival.AIM To explore the outcomes of pancreas transplants in the United States during the decade 2008-2018.METHODS Our study utilized the United Network for Organ Sharing Standard Transplant Analysis and Research file.Pre-and post-transplant recipient and waitlist characteristics and the most recent recipient transplant and mortality status were used.We included all patients with type I diabetes listed for pancreas or kidneypancreas transplant between May 31,2008 and May 31,2018.Patients were grouped into one of three transplant types:SPK,PAK,or PTA.RESULTS The adjusted Cox proportional hazards models comparing survival between transplanted and non-transplanted patients in each transplant type group showed that patients who underwent an SPK transplant exhibited a significantly reduced hazard of mortality[hazard ratio(HR)=0.21,95%confidence intervals(CI):0.19-0.25]compared to those not transplanted.Neither PAK transplanted patients(HR=1.68,95%CI:0.99-2.87)nor PTA patients(HR=1.01,95%CI:0.53-1.95)experienced significantly different hazards of mortality compared to patients who did not receive a transplant.CONCLUSION When assessing each of the three transplant types,only SPK transplant offered a survival advantage compared to patients on the waiting list.PKA and PTA transplanted patients demonstrated no significant differences compared to patients who did not receive a transplant.

Co-Inhibitors of Second Signal of Lymphocyte Response in Human Renal Transplants: PD-L2, GITR, and ILT-2/3/5 Positive Cells from Aspiration Biopsies Associate with Acute Rejection-Freedom

Following organ transplantation, the outcome of the encounter between an APC and a T lymphocyte is strongly dependent on the presence of costimulatory and co-inhibitory molecules, the former associated with allograft rejection and the latter with allograft acceptance. We evaluated the expression of PD-L2, GITR, ILT-2/3/5, and ILT-4 on graft-infiltrating cells procured by Fnab from human KTx under different immunosuppressive regimens. Methods: Fnab biopsies were performed on days 7 or 14 - 30 in stable KTx and on the day of acute rejection diagnosis. Cytopreparations were studied by the enzymatic avidin biotin complex staining. Results: Acute rejection group showed a significant down-regulated expression of PD-L2, GITR, and ILT-2/3/5 as compared to stable group, while for ILT-4 we did not find significant difference. Anti-IL2αR and rapamicyn treatment trend to down-regulate ILT-4 expression, although meaningless. A significantly positive correlation was observed between PD-L2 and GITR expression in Fnab. The PPV for acute rejection diagnosis for both PD-L2 and GITR was clearly above 0.8. Conclusions: Our findings point to an early entrance of cells expressing PD-L2, GITR and ILT-2/3/5 inside human KTx who are going to remain rejection-free. Both PD-L2 and GITR shared a high ability to rule-in and rule-out acute rejection.

Personality Characteristics among Patients Waiting for Liver or Kidney Transplants

Introduction: Personality characteristics are believed to predict post-transplant adherence and outcome. However, data concerning the prevalence and type of personality disorders (PDs) among transplant populations are sparse. Objectives: To evaluate the prevalence and types of PDs among patients waiting for liver or kidney transplants, to compare the results obtained between the two groups and to identify predictors of the prevalence of PDs. Method: In a prospective cohort study, 629 patients waiting for liver (n = 196) or kidney (n = 433) transplants were assessed by the Personality Diagnostic Questionnaire, fourth edition (PDQ-4+). Results: The 629 pre-transplant patients were 46.1 years old on average (SD: 11.5). The PDQ total score was 25.5 (SD: 13.7). 36.5% had a total score equal to or greater than 30. Paranoid (42.1%), avoidant (31.1%) and obsessive-compulsive (29.8%) were the most common possible PDs identified. Patients waiting for a kidney transplant had a higher total score than those waiting for a liver transplant (p 0.001) and they also had significantly more paranoid (p = 0.001), obsessive-compulsive (p = 0.002) and avoidant (p = 0.001) PDs. Comment: In case of possible PDs, an assessment of other clinical variables for helping patients is needed so that a specific treatment could be offered to patients at the time of their inclusion on the waiting list, during the waiting period and after the organ transplant.

Effects of LED light spectrum on the growth and energy use efficiency of eggplant transplants

To enhance the transplants’growth and reduce energy use efficiency,Eggplant(Solanum melongena L.)transplants(cv.Jingqie 21)were cultivated in a plant factory laboratory under different LED light spectrums.The experimental treatments included white plus blue LED lights(R:B=0.5,WB0.5),white LED lights(R:B=0.9,W0.9),white plus red LED lights(R:B=2.7,WR2.7),white plus red plus UV lights(R:B=3.8,WRUV3.8),and red plus blue plus green LED lights(R:B=5.4,RBG5.4).The transplants were grown for 30 d under a light intensity of 250μmol/m2·s and a photoperiod of 16 h/d.The morphological indicators and biomass accumulation of eggplant transplants were significantly higher in the W0.9 treatment compared to the other experimental treatments.The photosynthetic quantum yield in the W0.9 treatment exhibited an increase of over 22%compared to that in the WR2.7 treatment.The shoot dry weight of the W0.9 treatment reached(381±41)mg/plant and the leaf area was(113.3±8.9)cm^(2),indicating a higher health index compared to the other treatments.However,there were no significant differences in the net photosynthetic rate of the leaves among all treatments.The energy yield(EY)of the W0.9 treatment was(37.7±1.8)g/kW·h,which was higher than others.Therefore,considering the high quality of transplants and the maximization of energy use efficiency,the LED light spectrum in the eggplant transplants production was recommended to the white LED light with an R:B ratio of 0.9.

A systematic review of progenitor survival and maturation in Parkinsonian models

Stem cell-based brain repair is a promising emergent therapy for Parkinson's disease based on years of foundational research using human fetal donors as a cell source.Unlike current therapeutic options for patients,this approach has the potential to provide longterm stem cell–derived reconstruction and restoration of the dopaminergic input to denervated regions of the brain allowing for restoration of certain functions to patients.The ultimate clinical success of stem cell–derived brain repair will depend on both the safety and efficacy of the approach and the latter is dependent on the ability of the transplanted cells to survive and differentiate into functional dopaminergic neurons in the Parkinsonian brain.Because the pre-clinical literature suggests that there is considerable variability in survival and differentiation between studies,the aim of this systematic review was to assess these parameters in human stem cell-derived dopaminergic progenitor transplant studies in animal models of Parkinson's disease.A defined systematic search of the PubMed database was completed to identify relevant studies published up to March 2024.After screening,76 articles were included in the analysis from which 178 separate transplant studies were identified.From these,graft survival could be assessed in 52 studies and differentiation in 129 studies.Overall,we found that graft survival ranged from<1% to 500% of cells transplanted,with a median of 51%of transplanted cells surviving in the brain;while dopaminergic differentiation of the cells ranged from 0% to 46% of cells transplanted with a median of 3%.This systematic review suggests that there is considerable scope for improvement in the differentiation of stem cell-derived dopaminergic progenitors to maximize the therapeutic potential of this approach for patients.