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PURPOSE: To assess the safety and efficacy of ripasudil for retinopathy of prematurity (ROP). STUDY DESIGN: Phase 1/2, multicenter, open-label, single-arm, 12-week clinical trial. METHODS: Infants born with gestational age (GA) of ≤ 32 weeks or weight of ≤ 1500 g with zone I or II, ≥ stage 1, ROP in both eyes were enrolled. Ripasudil eye drops were administered to patients in both eyes. Phase 1 was a dose-escalation study (once daily for 1 week, then twice daily for 2 weeks); an additional dosing up to 9 weeks was allowed if no safety issues occurred. In phase 2, ripasudil was administered twice daily for up to 12 weeks. Adverse events were assessed. The proportion of patients with type 1 ROP progression, number of days for type 1 ROP progression, and progression to the most advanced ROP stage were estimated. RESULTS: Twenty-four infants were enrolled (phase 1, n = 3; phase 2, n = 21). Nineteen and four patients experienced systemic and ocular adverse events, respectively. Efficacy endpoints were not different between the ripasudil and historical control groups. However, in the GA ≤ 27 weeks subgroup, fewer patients progressed to type 1 ROP in the ripasudil than in the historical control group (P = 0.09). In the GA ≤ 27 weeks subgroups, the 25th percentile for the number of days for type 1 ROP progression was 22 days in the historical control group and 44 days in the ripasudil group. CONCLUSION: Ripasudil was safe and inhibited/delayed type 1 ROP progression, especially in infants with short GA.
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Objective: The objective of this paper is to reconsider the significance of preoperative chest radiography (CXR) before ophthalmic surgery through investigation of imaging findings and usage status. Methods: This retrospective observational clinical study involved 1616 patients who underwent ophthalmic surgery at Saga University Hospital from 1 January 2019 to 31 December 2020. The patients' radiology reports were obtained from the electronic medical records, and their CXR findings, therapeutic interventions, and progress were investigated. Results: Among all patients, 539 (33.4%) had abnormal preoperative CXR findings. Of these patients, 74 (4.6%) had newly identified abnormal findings. In both patient groups, approximately 70% of patients with abnormal findings were aged ≥70 years, and interstitial shadows were the most common finding. Among all patients with abnormal findings, three (0.19%) received preoperative therapeutic interventions, and all surgeries were performed safely. Forty-three patients with abnormal findings were referred to our hospital or other hospitals for further investigation and treatment postoperatively. Among those patients, eight (0.5%) had primary lung cancer, seven underwent surgery, and one received chemoradiation. The other patients were also followed up and received appropriate therapeutic interventions. Conclusions: Before ophthalmic surgery, few patients required actual therapeutic interventions based on their CXR results. However, many abnormal findings were revealed in elderly patients, including some serious diseases. Furthermore, research has suggested that appropriate therapeutic intervention after ophthalmologic surgery may reduce the risk of a poor life prognosis. This study clearly shows that preoperative CXR is not only useful for perioperative systemic management but also ultimately benefits patients. It is also considered particularly meaningful for patients aged ≥70 years.
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Human iPSC-derived cardiomyocytes (hiPSC-CMs) exhibit functional immaturity, potentially impacting their suitability for assessing drug proarrhythmic potential. We previously devised a traveling wave (TW) system to promote maturation in 3D cardiac tissue. To align with current drug assessment paradigms (CiPA and JiCSA), necessitating a 2D monolayer cardiac tissue, we integrated the TW system with a multi-electrode array. This gave rise to a hiPSC-derived closed-loop cardiac tissue (iCT), enabling spontaneous TW initiation and swift pacing of cardiomyocytes from various cell lines. The TW-paced cardiomyocytes demonstrated heightened sarcomeric and functional maturation, exhibiting enhanced response to isoproterenol. Moreover, these cells showcased diminished sensitivity to verapamil and maintained low arrhythmia rates with ranolazine-two drugs associated with a low risk of torsades de pointes (TdP). Notably, the TW group displayed increased arrhythmia rates with high and intermediate risk TdP drugs (quinidine and pimozide), underscoring the potential utility of this system in drug assessment applications.
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is missing (Short communication).
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Toxidermias , Humanos , Toxidermias/diagnóstico , Toxidermias/etiologia , Mucosa , NarizRESUMO
BACKGROUND: Heart failure (HF) is a major cause of death worldwide. The most effective treatment for HF is heart transplantation, but its use is limited by the scarcity of donor hearts. Recently, stem cell-based therapy has emerged as a promising approach for treating myocardial infarction. Our research group has been investigating the use of human induced pluripotent stem cell-derived cardiomyocyte patches as a potential therapeutic candidate. We have successfully conducted eight cases of clinical trials and demonstrated the safety and effectiveness of this approach. However, further advancements are necessary to overcome immune rejection and enhance therapeutic efficacy. In this study, we propose a novel and efficient technique for constructing mesenchymal stem cell (MSC) tissue sheets, which can be transplanted effectively for treating myocardial infarction repair. METHODS: We applied a one-step method to construct the human adipose-derived mesenchymal stem cell (hADSC) tissue sheet on a poly(lactic-co-glycolic acid) fiber scaffold. Histology, immunofluorescence, and paracrine profile assessment were used to determine the organization and function of the hADSC tissue sheet. Echocardiography and pathological analyses of heart sections were performed to evaluate cardiac function, fibrosis area, angiogenesis, and left ventricular remodeling. RESULTS: In vitro, the hADSC tissue sheet showed great organization, abundant ECM expression, and increased paracrine secretion than single cells. In vivo, the hADSC tissue sheet group demonstrated improved cardiac functional recovery, less ventricular remodeling, decreased fibrosis, and enhanced angiogenesis than the MI group. CONCLUSIONS: We developed thick and functional hADSC tissue sheets via the one-step strategy. The hADSC tissue sheet showed excellent performance in treating myocardial infarction in the rat model.
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Insuficiência Cardíaca , Transplante de Coração , Células-Tronco Pluripotentes Induzidas , Transplante de Células-Tronco Mesenquimais , Infarto do Miocárdio , Humanos , Ratos , Animais , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Pluripotentes Induzidas/metabolismo , Doadores de Tecidos , Infarto do Miocárdio/patologia , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/patologia , FibroseRESUMO
BACKGROUND: Transplanting human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) tissue sheets effectively treat ischemic cardiomyopathy. Cardiac functional recovery relies on graft survival in which angiogenesis played an important part. ONO-1301 is a synthetic prostacyclin analog with proangiogenic effects. We hypothesized that transplantation of hiPSC-CM tissue sheets with slow-release ONO-1301 scaffold could promote hostgraft angiogenesis, enhance tissue survival and therapeutic effect. METHODS: We developed hiPSC-CM tissue sheets with ONO-1301 slow-release scaffold and evaluated their morphology, gene expression, and effects on angiogenesis. Three tissue sheet layers were transplanted into a rat myocardial infarction (MI) model. Left ventricular ejection fraction, gene expression in the MI border zone, and angiogenesis effects were investigated 4 weeks after transplantation. RESULTS: In vitro assessment confirmed the slow-release of ONO-1301, and its pro-angiogenesis effects. In addition, in vivo data demonstrated that ONO-1301 administration positively correlated with graft survival. Cardiac tissue as thick as â¼900 µm was retained in the ONO (+) treated group. Additionally, left ventricular ejection fraction of the ONO (+) group was significantly enhanced, compared to ONO (-) group. The ONO (+) group also showed significantly improved interstitial fibrosis, higher capillary density, increased number of mature blood vessels, along with an enhanced supply of oxygen, and nutrients. CONCLUSIONS: Slow-release ONO-1301 scaffold provided an efficient delivery method for thick hiPSC-CM tissue. ONO-1301 promotes angiogenesis between the host and graft and improves nutritional and oxygen supply, thereby enhancing the survival of transplanted cells, effectively improving ejection fraction, and therapeutic effects.
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Células-Tronco Pluripotentes Induzidas , Infarto do Miocárdio , Humanos , Ratos , Animais , Células-Tronco Pluripotentes Induzidas/transplante , Volume Sistólico , Indutores da Angiogênese/farmacologia , Função Ventricular Esquerda , Infarto do Miocárdio/terapia , Miócitos Cardíacos/metabolismo , Modelos Animais de DoençasRESUMO
Diabetic foot ulceration is a common chronic diabetic complication. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have been widely used in regenerative medicine owing to their multipotency and easy availability. We developed poly(lactic-co-glycolic acid) (PLGA)-based scaffold to create hUC-MSC tissue sheets. In vitro immunostaining showed that hUC-MSC tissue sheets formed thick and solid tissue sheets with an abundance of extracellular matrix (ECM). Diabetic wounds in mice treated with or without either the hUC-MSC tissue sheet, hUC-MSC injection, or fiber only revealed that hUC-MSC tissue sheet transplantation promoted diabetic wound healing with improved re-epithelialization, collagen deposition, blood vessel formation and maturation, and alleviated inflammation compared to that observed in other groups. Taken collectively, our findings suggest that hUC-MSCs cultured on PLGA scaffolds improve diabetic wound healing, collagen deposition, and angiogenesis, and provide a novel and effective method for cell transplantation, and a promising alternative for diabetic skin wound treatment.
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Diabetes Mellitus , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Humanos , Camundongos , Animais , Transplante de Células-Tronco Mesenquimais/métodos , Cordão Umbilical , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Cicatrização , ColágenoRESUMO
Retinitis pigmentosa (RP) is an intractable inherited disease that primarily affects the rods through gene mutations followed by secondary cone degeneration. This cone-related dysfunction can lead to impairment of daily life activities, and ultimately blindness in patients with RP. Paradoxically, microglial neuroinflammation contributes to both protection against and progression of RP, but it is unclear which population(s) - tissue-resident microglia and/or peripheral monocyte-derived macrophages (mφ) - are implicated in the progression of the disease. Here we show that circulating blood inflammatory monocytes (IMo) are key effector cells that mediate cone cell death in RP. Attenuation of IMo and peripherally engrafted mφ by Ccl2 deficiency or immune modulation via intravenous nano-particle treatment suppressed cone cell death in rd10 mice, an animal model of RP. In contrast, the depletion of resident microglia by a colony-stimulating factor 1 receptor inhibitor exacerbated cone cell death in the same model. In human patients with RP, IMo was increased and correlated with disease progression. These results suggest that peripheral IMo is a potential target to delay cone cell death and prevent blindness in RP.
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Clinical use of human pluripotent stem cells (hPSCs) is hampered by the technical limitations of their expansion. Here, we developed a chemically synthetic culture substrate for human pluripotent stem cell attachment and maintenance. The substrate comprises a hydrophobic polyvinyl butyral-based polymer (PVB) and a short peptide that enables easy and uniform coating of various types of cell culture ware. The coated ware exhibited thermotolerance, underwater stability and could be stored at room temperature. The substrate supported hPSC expansion in combination with most commercial culture media with an efficiency similar to that of commercial substrates. It supported not only the long-term expansion of examined iPS and ES cell lines with normal karyotypes during their undifferentiated state but also directed differentiation of three germ layers. This substrate resolves major concerns associated with currently used recombinant protein substrates and could be applied in large-scale automated manufacturing; it is suitable for affordable and stable production of clinical-grade hPSCs and hPSC-derived products.
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Técnicas de Cultura de Células/métodos , Diferenciação Celular/efeitos dos fármacos , Autorrenovação Celular/efeitos dos fármacos , Células-Tronco Embrionárias Humanas/citologia , Células-Tronco Pluripotentes Induzidas/citologia , Peptídeos/farmacologia , Polivinil/farmacologia , Alicerces Teciduais/química , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Células-Tronco Embrionárias Humanas/efeitos dos fármacos , Células-Tronco Embrionárias Humanas/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Células-Tronco Pluripotentes Induzidas/metabolismo , Peptídeos/metabolismo , Polivinil/metabolismoAssuntos
Psoríase , Dermatopatias , Humanos , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Pele , TioidantoínasAssuntos
Doenças da Coroide/cirurgia , Corioide/irrigação sanguínea , Fotocoagulação a Laser/métodos , Pólipos/cirurgia , Idoso de 80 Anos ou mais , Corioide/diagnóstico por imagem , Doenças da Coroide/diagnóstico , Feminino , Fóvea Central/diagnóstico por imagem , Humanos , Pólipos/diagnóstico , Tomografia de Coerência Óptica/métodosRESUMO
PURPOSE: To investigate the long-term outcomes of cataract surgery in patients with retinitis pigmentosa (RP). DESIGN: Retrospective, observational study. PARTICIPANTS: Sixty-four patients with typical RP (22 men, 42 women; average age, 62.8 ± 10.1 years) who underwent cataract surgery at Kyushu University Hospital between May 2007 and October 2015 and were followed up for ≥3 years after the surgery. METHODS: Differences between presurgery and postsurgery visual function, including best-corrected visual acuity (BCVA) and parameters in the Humphrey field analyzer (HFA) examination using the central 10-2 program, were investigated. The presurgery conditions of the foveal ellipsoid zone (EZ) were classified into 3 grades (grade 1: invisible; grade 2: abnormal; grade 3: normal) based on OCT findings. MAIN OUTCOME MEASURES: BCVA, the retinal sensitivity in the HFA 10-2 test. RESULTS: Cataract surgery was performed in 96 eyes, with an average follow-up period of 5.8 ± 2.4 years. The mean presurgery BCVA was 0.64 ± 0.52 logarithm of the minimum angle of resolution (logMAR), and the final postsurgery BCVA was 0.61 ± 0.67 logMAR (P = 0.57). Significant improvement in the postsurgery BCVA was observed only in eyes with preserved foveal EZ (grade 3) (P < 0.01). In 62 eyes of 45 patients who underwent the HFA 10-2 test, the mean values of deviation, macular sensitivity, and foveal sensitivity at the final visit were significantly decreased compared with preoperative values (P < 0.01), whereas those in grade 3 eyes did not change significantly after the surgery (P = 0.13). CONCLUSIONS: In the long-term course after cataract surgery in patients with RP, many patients experienced vision loss with progression of the disease. The preoperative finding of preserved foveal EZ was associated with a better visual prognosis, suggesting that EZ evaluation is useful for predicting the long-term visual outcome of cataract surgery in patients with RP.
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Catarata , Retinose Pigmentar , Idoso , Catarata/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Retinose Pigmentar/complicações , Retinose Pigmentar/diagnóstico , Retinose Pigmentar/cirurgia , Estudos Retrospectivos , Tomografia de Coerência Óptica , Acuidade VisualRESUMO
PURPOSE: To investigate the rate of the recurrence of cystoid macular edema (CME) secondary to retinitis pigmentosa (RP) after the initiation of topical dorzolamide and the recurrence risk factors. METHODS: We retrospectively analyzed the data of RP patients at Kyushu University Hospital. We included patients who showed a treatment response to 1.0% topical dorzolamide. The day of treatment initiation was set as the baseline. Topical dorzolamide treatment was continued during the follow-up. The recurrence of CME (defined as a >20% increase in central subfield thickness compared to previous visit, or a central subfield thickness value that exceed baseline value) was evaluated at each follow-up visit. Risk factors for RP-CME recurrence were analyzed by Cox proportional hazards modeling. A Kaplan-Meier survival analysis was used to evaluate the time to recurrent RP-CME. RESULTS: Forty RP-CME patients showed a treatment response to topical dorzolamide. During the mean 3.9-year follow-up, 14 patients exhibited recurrence; its rate was 15.6%, 34.7%, and 48.7% at 1, 3, and 5 years, respectively. A high baseline central subfield thickness was significantly associated with recurrent (hazard ratio 1.11, 95% CI: 1.05-1.18, P = 0.0004). CONCLUSION: The recurrence rate of RP-CME increased with time. A high baseline central subfield thickness value was a risk factor for recurrence.
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Macula Lutea/crescimento & desenvolvimento , Edema Macular/epidemiologia , Retinose Pigmentar/complicações , Medição de Risco/métodos , Sulfonamidas/administração & dosagem , Tiofenos/administração & dosagem , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Administração Tópica , Inibidores da Anidrase Carbônica/administração & dosagem , Feminino , Seguimentos , Humanos , Incidência , Japão/epidemiologia , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Retinose Pigmentar/diagnóstico , Fatores de Risco , Fatores de TempoRESUMO
INTRODUCTION: Retinopathy of prematurity (ROP) is a vascular proliferative disorder that occurs in preterm infants. Existing treatments are only indicated in severe ROP cases due to the high invasiveness and the potential risk of irreversible side effects. We previously elucidated that ripasudil, a selective inhibitor of the Rho-associated protein kinase, has the ability to inhibit abnormal retinal neovascularisation in animal models. In addition, ripasudil eye drops (Glanatec ophthalmic solution 0.4%) have been already used for the treatment of glaucoma. Since eye drop therapy is less invasive, early intervention for ROP is possible. The purpose of this phase I/II trial is to evaluate the safety and efficacy of ripasudil eye drops for preterm infants with ROP. METHODS AND ANALYSIS: This is a multicentre, open-label, single-arm phase I/II trial. To evaluate the safety and efficacy of ripasudil as much as possible, ripasudil will be administered to all enrolled preterm infants with zone I/II, stage 1, or worse ROP. The safety and efficacy of ripasudil in treated patients will be assessed in comparison to a historical control group. Because this is the first trial of ripasudil in preterm infants, a dose-escalation study (once daily for 1 week, then two times per day for 2 weeks) will be conducted in phase I. After obtaining approval from the independent data and safety monitoring board to continue the trial after the completion of phase I, phase II will be conducted. In phase II, ripasudil eye drops will be administered two times per day for 12 weeks. The primary endpoint in phase II is also safety. Efficacy and pharmacokinetics will be evaluated as secondary endpoints. ETHICS AND DISSEMINATION: This study protocol was approved by the institutional review board at each of the participating centres. Data will be presented at international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBERS: NCT04621136 and jRCT2071200047.
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Retinopatia da Prematuridade , Animais , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Isoquinolinas/efeitos adversos , Estudos Multicêntricos como Assunto , Soluções Oftálmicas , Retinopatia da Prematuridade/tratamento farmacológico , Sulfonamidas , Resultado do TratamentoRESUMO
AIMS: To examine the association of dipstick hematuria with kidney function and albuminuria in patients with type 2 diabetes (T2D). METHODS: A total of 7,945 patients with T2D were studied. In the cross-sectional study, patients were classified into 6 groups based on the stage of albuminuria and estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73 m2 at baseline. In the longitudinal study where patients were classified by the presence of hematuria, the primary composite endpoint was a 30% decrease in eGFR from baseline or the initiation of kidney replacement therapy. Other outcomes included eGFR slope and stage progression of albuminuria. RESULTS: Cross-sectionally, hematuria was more prevalent in patients with more advanced stages of albuminuria and with lower eGFR, independently of each other. In the longitudinal study, patients with hematuria experienced 50% increased incidence of the primary endpoint (p < 0.001). The eGFR slope was steeper in patients with hematuria than in those without hematuria (p < 0.001). On the other hand, hematuria was unlikely to be associated with the progression of albuminuria. CONCLUSIONS: In patients with T2D, dipstick hematuria was associated with prevalent albuminuria and reduced eGFR, as well as faster decline in kidney function but not higher risk of development or progression of albuminuria.
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Diabetes Mellitus Tipo 2/complicações , Hematúria/etiologia , Insuficiência Renal Crônica/complicações , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: To elucidate the differences in autonomic dysfunction between dementia with Lewy bodies (DLB) and Alzheimer's disease using a simple and convenient method, we investigated the heart rate response to orthostatic challenge. METHODS: Ninety-seven people participated in this cross-sectional study, and data from 26 DLB patients, 29 Alzheimer's disease patients, and 25 healthy elderly individuals were analysed. Participants underwent postural changes, including 5 min in a supine position, 1 min in a sitting position, and 3 min in an orthostatic position. Their heart rates were continuously recorded. Two heart rate variables were analysed as main outcomes: (i) the difference between heart rate in the sitting position and the peak heart rate within 15 s of orthostasis, defined as the 'early heart rate increase'; and (ii) the difference between the peak heart rate and the negative peak heart rate after this, defined as 'early heart rate recovery.' An early heart rate increase has been considered to reflect parasympathetic and sympathetic functions. Early heart rate recovery is considered to reflect parasympathetic function. We also investigated the frequency domains of resting heart rate variability. RESULTS: A significant difference was observed across the three groups in early heart rate increase, and that of the DLB group was lower than that of the healthy control group. Early heart rate recovery also differed significantly across the three groups, and that of the DLB group was less than that of the healthy control group. In addition, the power of the low-frequency component, which represents both sympathetic and parasympathetic activity, was significantly decreased in the DLB group compared to the Alzheimer's disease group. CONCLUSIONS: Impaired heart rate response to standing was detected in patients with DLB. Electrocardiogram is a convenient, non-invasive method that might be useful as a subsidiary marker for DLB diagnosis and differentiation from Alzheimer's disease.
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Doença de Alzheimer , Frequência Cardíaca , Hipotensão Ortostática , Doença por Corpos de Lewy , Idoso , Doença de Alzheimer/diagnóstico , Estudos Transversais , Humanos , Hipotensão Ortostática/diagnóstico , Doença por Corpos de Lewy/diagnóstico , Teste da Mesa InclinadaRESUMO
Purpose: To investigate the association between aqueous flare and progression of visual field loss using the Humphrey Field Analyzer in patients with retinitis pigmentosa (RP). Methods: We examined a total of 101 eyes of 101 patients who were diagnosed with typical RP. Sixty-one percent of the patients were female, and the mean age of the total group was 47.4 years. Aqueous flare, visual field (by an Humphrey Field Analyzer, the central 10-2 SITA-Standard program), and optical coherence tomography measurements were obtained for all patients. The slope, which was derived from serial values of mean deviation, macular sensitivity, or foveal sensitivity for each eye with univariate linear regression, was used for analysis. Results: Aqueous flare values were significantly correlated with the mean deviation slope (r = -0.20, P = 0.046), macular sensitivity slope (r = -0.28, P = 0.005) and foveal sensitivity slope (r = -0.20, P = 0.047). The values of the retinal sensitivity slope significantly decreased as the aqueous flare level increased (all P < 0.05). These associations remained unchanged after adjustment for age, sex, and posterior subcapsular cataract, and epiretinal membrane. Conclusions: Elevation of aqueous flare is a risk factor for the decline of central visual function in RP. Aqueous flare may be a useful marker for disease progression in RP.
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Humor Aquoso , Retina , Retinose Pigmentar , Transtornos da Visão , Acuidade Visual , Barreira Hematorretiniana , Correlação de Dados , Progressão da Doença , Eletrorretinografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Retina/diagnóstico por imagem , Retina/fisiopatologia , Retinose Pigmentar/diagnóstico , Retinose Pigmentar/fisiopatologia , Tomografia de Coerência Óptica/métodos , Transtornos da Visão/diagnóstico , Transtornos da Visão/etiologia , Transtornos da Visão/fisiopatologia , Testes de Campo Visual/métodosRESUMO
BACKGROUND: Vivax malaria is associated with significant morbidity and economic loss, and constitutes the bulk of malaria cases in large parts of Asia and South America as well as recent case reports in Africa. The widespread prevalence of vivax is a challenge to global malaria elimination programmes. Vivax malaria control is particularly challenged by existence of dormant liver stage forms that are difficult to treat and are responsible for multiple relapses, growing drug resistance to the asexual blood stages and host-genetic factors that preclude use of specific drugs like primaquine capable of targeting Plasmodium vivax liver stages. Despite an obligatory liver-stage in the Plasmodium life cycle, both the difficulty in obtaining P. vivax sporozoites and the limited availability of robust host cell models permissive to P. vivax infection are responsible for the limited knowledge of hypnozoite formation biology and relapse mechanisms, as well as the limited capability to do drug screening. Although India accounts for about half of vivax malaria cases world-wide, very little is known about the vivax liver stage forms in the context of Indian clinical isolates. METHODS: To address this, methods were established to obtain infective P. vivax sporozoites from an endemic region in India and multiple assay platforms set up to detect and characterize vivax liver stage forms. Different hepatoma cell lines, including the widely used HCO4 cells, primary human hepatocytes as well as hepatocytes obtained from iPSC's generated from vivax patients and healthy donors were tested for infectivity with P. vivax sporozoites. RESULTS: Both large and small forms of vivax liver stage are detected in these assays, although the infectivity obtained in these platforms are low. CONCLUSIONS: This study provides a proof of concept for detecting liver stage P. vivax and provide the first characterization of P. vivax liver stage forms from an endemic region in India.