Cell Transplantation最新文献

{"title":"Changes in the Proportion of Each Cell Type After hiPSC-Derived Airway Epithelia Transplantation.","authors":"Masayuki Kitano, Yasuyuki Hayashi, Hiroe Ohnishi, Hideaki Okuyama, Masayoshi Yoshimatsu, Keisuke Mizuno, Fumihiko Kuwata, Takeshi Tada, Yo Kishimoto, Satoshi Morita, Koichi Omori","doi":"10.1177/09636897241228026","DOIUrl":"10.1177/09636897241228026","url":null,"abstract":"<p><p>No radical treatment is available for the regeneration of dysfunction and defects in airway epithelia. Artificial tracheae made of polypropylene and collagen sponge were used in clinical studies to reconstitute tracheae after resection. For early epithelialization of the luminal surface of the artificial trachea, a model was established, that is, an artificial trachea covered with human-induced pluripotent stem cell-derived airway epithelial cells (hiPSC-AECs) was transplanted into a tracheal defect in an immunodeficient rat. Unlike the cell types of hiPSC-derived cells that are currently used in clinical studies, AECs maintain tissues by proliferation and differentiation of basal cells into various cell types that constitute AECs constantly. Therefore, post-transplantation, the proportion of each cell type, such as ciliated and goblet cells, may change; however, no studies have examined this possibility. In this study, using our hiPSC-AEC-transplanted rat model, we investigated changes in the proportion of each cell type in hiPSC-AECs pre-transplantation and post-transplantation. As a result, the proportion of each cell type changed post-transplantation. The proportion of ciliated, basal, and club cells increased, and the proportion of goblet cells decreased post-transplantation. In addition, the proportion of each cell type in engrafted hiPSC-AECs is more similar to the proportion of each cell type in normal proximal airway tissue than the proportion of each cell type pre-transplantation. The results of this study are useful for the development of therapeutic techniques using hiPSC-AEC transplantation.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241228026"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10878204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139899408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Therapeutic Potential of Peritoneal Dialysis (PD) in the Treatment of Neurological Disorders.","authors":"Muyuan Cheng, Yuchuan Ding, Enoch Kim, Xiaokun Geng","doi":"10.1177/09636897241236576","DOIUrl":"10.1177/09636897241236576","url":null,"abstract":"<p><p>Peritoneal dialysis (PD) is a well-established renal replacement therapy commonly employed in clinical practice. While its primary application is in the treatment of kidney disease, its potential in addressing other systemic disorders, including neurological diseases, has garnered increasing interest. This study provides a comprehensive overview of the related technologies, unique advantages, and clinical applications of PD in the context of neurological disorders. By exploring the mechanism underlying PD, its application in neurological diseases, and associated complications, we addressed the feasibility and benefits of PD as an adjunct therapy for various neurological conditions. Our study aims to highlight its role in detoxification and symptom management, as well as its advantages over other universally accepted methods of renal replacement therapy. Our goal is to bring to the spotlight the therapeutic potential of PD in neurological diseases, such as stroke, stimulate further research, and broaden the scope of its application in the clinical setting.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241236576"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10956140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140173786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelet Concentrates Preconditioning of Mesenchymal Stem Cells and Combined Therapies: Integrating Regenerative Strategies for Enhanced Clinical Applications.","authors":"Xu-Huan Li, Han-Xi Xiao, Zu-Xiu Wang, Xin-Rong Tang, Xue-Feng Yu, Yong-Ping Pan","doi":"10.1177/09636897241235460","DOIUrl":"10.1177/09636897241235460","url":null,"abstract":"<p><p>This article presents a comprehensive review of the factors influencing the efficacy of mesenchymal stem cells (MSCs) transplantation and its association with platelet concentrates (PCs). It focuses on investigating the impact of PCs' composition, the age and health status of platelet donors, application methods, and environmental factors on the outcomes of relevant treatments. In addition, it delves into the strategies and mechanisms for optimizing MSCs transplantation with PCs, encompassing preconditioning and combined therapies. Furthermore, it provides an in-depth exploration of the signaling pathways and proteomic characteristics associated with preconditioning and emphasizes the efficacy and specific effects of combined therapy. The article also introduces the latest advancements in the application of biomaterials for optimizing regenerative medical strategies, stimulating scholarly discourse on this subject. Through this comprehensive review, the primary goal is to facilitate a more profound comprehension of the factors influencing treatment outcomes, as well as the strategies and mechanisms for optimizing MSCs transplantation and the application of biomaterials in regenerative medicine, offering theoretical guidance and practical references for related research and clinical practice.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241235460"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10956156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140173787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transplantation and Noninvasive Longitudinal <i>In Vivo</i> Imaging of Parathyroid Cells: A Proof-of-Concept Study.","authors":"Robert Bränström, Pim P van Krieken, Robin Fröbom, C Christofer Juhlin, Ivan Shabo, Barbara Leibiger, Ingo B Leibiger, Per-Olof Berggren, Craig A Aspinwall","doi":"10.1177/09636897241241995","DOIUrl":"10.1177/09636897241241995","url":null,"abstract":"<p><p>The parathyroid cell is a vital regulator of extracellular calcium levels, operating through the secretion of parathyroid hormone (PTH). Despite its importance, the regulation of PTH secretion remains complex and not fully understood, representing a unique interplay between extracellular and intracellular calcium, and hormone secretion. One significant challenge in parathyroid research has been the difficulty in maintaining cells <i>ex vivo</i> for in-depth cellular investigations. To address this issue, we introduce a novel platform for parathyroid cell transplantation and noninvasive <i>in vivo</i> imaging using the anterior chamber of the eye as a transplantation site. We found that parathyroid adenoma tissue transplanted into the mouse eye engrafted onto the iris, became vascularized, and retained cellular composition. Transplanted animals exhibited elevated PTH levels, indicating a functional graft. With <i>in vivo</i> confocal microscopy, we were able to repetitively monitor parathyroid graft morphology and vascularization. In summary, there is a pressing need for new methods to study complex cellular processes in parathyroid cells. Our study provides a novel approach for noninvasive <i>in vivo</i> investigations that can be applied to understand parathyroid physiology and pathology under physiological and pathological conditions. This innovative strategy can deepen our knowledge on parathyroid function and disease.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241241995"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10981846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140329702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hematopoietic Stem Cell Transplantation in the Management of Myelodysplastic Syndrome: A Retrospective, Current, and Future Perspective.","authors":"Qimudesiren, Wenjie Yin, Yuhong Wang, Guo Qing, Jinhua Bao, Chaomurilige, Shana Chen, Liren Qian","doi":"10.1177/09636897241284283","DOIUrl":"10.1177/09636897241284283","url":null,"abstract":"<p><p>Myelodysplastic syndrome (MDS) is a clonal disorder that affects hematopoietic stem cells (HSCs), primarily occurring in the elderly population. Lower-risk MDS is characterized by a decrease in blood cells, whereas higher-risk MDS is associated with an increased risk of transformation to acute myeloid leukemia (AML). Currently, the treatment of MDS is still unsatisfactory, although demethylating agents, azacitidine (AZA), and decitabine (Dec) have been successfully used to treat MDS and improve survival rates. However, hematopoietic stem cell transplantation (HSCT) remains the only curative treatment for MDS patients, effectively increasing patient survival and quality of life. Nevertheless, treatment-related toxicity, graft-versus-host disease, infectious complications, and relapse are still major post-transplant issues. In this review, through a retrospective analysis of past and present HSCT for the treatment of MDS, we provide insights for the future.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241284283"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xenogenic Engraftment of Human-Induced Pluripotent Stem Cell-Derived Pancreatic Islet Cells in an Immunosuppressive Diabetic Göttingen Mini-Pig Model.","authors":"Midori Yamasaki, Toshiyuki Maki, Taisuke Mochida, Teruki Hamada, Saori Watanabe-Matsumoto, Shuhei Konagaya, Manami Kaneko, Ryo Ito, Hikaru Ueno, Taro Toyoda","doi":"10.1177/09636897241288932","DOIUrl":"https://doi.org/10.1177/09636897241288932","url":null,"abstract":"<p><p>In the development of cell therapy products, immunocompromised animal models closer in size to humans are valuable for enhancing the translatability of <i>in vivo</i> findings to clinical trials. In the present study, we generated immunocompromised type 1 diabetic Göttingen mini-pig models and demonstrated the engraftment of human-induced pluripotent stem cell-derived pancreatic islet cells (iPICs). We induced hyperglycemia with a concomitant reduction in endogenous C-peptide levels in pigs that underwent thymectomy and splenectomy. After estimating the effective <i>in vivo</i> dose of immunosuppressants (ISs) via <i>in vitro</i> testing, we conducted exploratory implantation of iPICs using various implantation methods under IS treatments in one pig. Five weeks after implantation, histological analysis of the implanted iPICs embedded in fibrin gel revealed numerous islet-like structures with insulin-positive cells. Moreover, the area of the insulin-positive cells in the pre-peritoneally implanted grafts was greater than in the subcutaneously implanted grafts. Immunohistochemical analyses further revealed that these iPIC grafts contained cells positive for glucagon, somatostatin, and pancreatic polypeptides, similar to naturally occurring islets. The engraftment of iPICs was successfully reproduced. These data support the observation that the iPICs engrafted well, particularly in the pre-peritoneal space of the newly generated immunocompromised diabetic mini-pigs, forming islet-like endocrine clusters. Future evaluation of human cells in this immunocompromised pig model could accelerate and development of cell therapy products.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241288932"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11489945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiomimetic Fluidic Culture Platform on Microwell-Patterned Porous Collagen Scaffold for Human Pancreatic Islets.","authors":"Hiroyuki Kato, Huajian Chen, Kuang-Ming Shang, Kenji Izumi, Naoya Koba, Takanori Tsuchiya, Naoki Kawazoe, Janine Quijano, Keiko Omori, Chris Orr, Meirigeng Qi, Hsun Teresa Ku, Fouad Kandeel, Yu-Chong Tai, Guoping Chen, Hirotake Komatsu","doi":"10.1177/09636897241249556","DOIUrl":"10.1177/09636897241249556","url":null,"abstract":"<p><p>Pancreatic islet transplantation is one of the clinical options for certain types of diabetes. However, difficulty in maintaining islets prior to transplantation limits the clinical expansion of islet transplantations. Our study introduces a dynamic culture platform developed specifically for primary human islets by mimicking the physiological microenvironment, including tissue fluidics and extracellular matrix support. We engineered the dynamic culture system by incorporating our distinctive microwell-patterned porous collagen scaffolds for loading isolated human islets, enabling vertical medium flow through the scaffolds. The dynamic culture system featured four 12 mm diameter islet culture chambers, each capable of accommodating 500 islet equivalents (IEQ) per chamber. This configuration calculates > five-fold higher seeding density than the conventional islet culture in flasks prior to the clinical transplantations (442 vs 86 IEQ/cm²). We tested our culture platform with three separate batches of human islets isolated from deceased donors for an extended period of 2 weeks, exceeding the limits of conventional culture methods for preserving islet quality. Static cultures served as controls. The computational simulation revealed that the dynamic culture reduced the islet volume exposed to the lethal hypoxia (< 10 mmHg) to ~1/3 of the static culture. Dynamic culture ameliorated the morphological islet degradation in long-term culture and maintained islet viability, with reduced expressions of hypoxia markers. Furthermore, dynamic culture maintained the islet metabolism and insulin-secreting function over static culture in a long-term culture. Collectively, the physiological microenvironment-mimetic culture platform supported the viability and quality of isolated human islets at high-seeding density. Such a platform has a high potential for broad applications in cell therapies and tissue engineering, including extended islet culture prior to clinical islet transplantations and extended culture of stem cell-derived islets for maturation.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241249556"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11095165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strategy for Clinical Setting of Co-transplantation of Mesenchymal Stem Cells and Pancreatic Islets.","authors":"Liang Mei, Yang Yuwei, Liang Weiping, Xu Zhiran, Feng Bingzheng, Chen Jibing, Gao Hongjun","doi":"10.1177/09636897241259433","DOIUrl":"10.1177/09636897241259433","url":null,"abstract":"<p><p>Islet transplantation may be the most efficient therapeutic technique for patients with type 1 diabetes mellitus (T1DM). However, the clinical application of this method is faced with numerous limitations, including isolated islet apoptosis, recipient rejection, and graft vascular reconstruction. Mesenchymal stem cells (MSCs) possess anti-apoptotic, immunomodulatory, and angiogenic properties. Here, we review recent studies on co-culture and co-transplantation of islets with MSCs. We have summarized the methods of preparation of co-transplantation, especially the merits of co-culture, and the effects of co-transplantation. Accumulating experimental evidence shows that co-culture of islets with MSCs promotes islet survival, enhances islet secretory function, and prevascularizes islets through various pretransplant preparations. This review is expected to provide a reference for exploring the use of MSCs for clinical islet co-transplantation.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241259433"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11179456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel JAK1 Inhibitor SHR0302 Combined With Prednisone for First-Line Treatment of Chronic Graft-Versus-Host Disease: A Phase I Clinical Trial.","authors":"Qiaomei He, Xi Sun, Jiahua Niu, Jun Yang, Ying Wang, Chongmei Huang, Kun Zhou, Yin Tong, Yu Cai, Baoxia Dong, Liping Wan, Xianmin Song, Huiying Qiu","doi":"10.1177/09636897241254678","DOIUrl":"10.1177/09636897241254678","url":null,"abstract":"<p><p>Chronic graft-versus-host disease (cGVHD) is a potentially life-threatening complication after allogeneic hematopoietic stem cell transplantation. Standard steroid first-line treatment could not satisfy therapeutic needs due to limited efficacy. As a highly selective Janus kinase (JAK) 1 inhibitor, SHR0302 exhibits a reduced inhibition effect on JAK2 and might have less effect on hematopoiesis. This phase I clinical trial investigated the tolerability and safety of SHR0302 in combination with prednisone, and its early efficacy evidence as a potential first-line treatment to moderate/severe cGVHD. The standard 3 + 3 dose escalation was implemented to find the optimal dose of SHR0302. And prednisone was concurrently administrated with a dose of 1 mg/kg/d and then gradually tapered after 2 weeks. Eighteen patients were enrolled into the study. Grade ≥ 3 treatment-related adverse events were observed in 38.9% of patients. Only one patient developed DLT (grade ≥ 3 hypercholesterolemia) in the highest dose-level group who had pre-existing hypercholesterolemia. The maximum tolerated dose was not reached. No patient discontinued treatment due to AEs. Sixteen out of 18 patients were evaluable for responses, the ORR at week 4 and week 24 were 94.4 and 87.5%, respectively. Overall, the treatment of SHR0302 combined with prednisone was safe and well-tolerated, preliminary clinical results presented a high response for previously untreated cGVHD and a significant reduction in prednisone use in this study. A phase II trial will be conducted to further investigate its therapeutic effects clinically.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241254678"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11129572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Basiliximab Treatment for Patients With Steroid-Refractory Acute Graft-Versus-Host Disease Following Matched Sibling Donor Hematopoietic Stem Cell Transplantation.","authors":"Xin-Ya Jiang, Xiao-Hui Zhang, Lan-Ping Xu, Yu Wang, Chen-Hua Yan, Huan Chen, Yu-Hong Chen, Wei Han, Feng-Rong Wang, Jing-Zhi Wang, Yu-Qian Sun, Xiao-Dong Mo, Xiao-Jun Huang","doi":"10.1177/09636897241257568","DOIUrl":"10.1177/09636897241257568","url":null,"abstract":"<p><p>Basiliximab is an important treatment for steroid-refractory acute graft-versus-host disease (SR-aGVHD). We performed this retrospective study to evaluate the efficacy and safety of basiliximab treatment in SR-aGVHD patients following matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) (<i>n</i> = 63). Overall response rate (ORR) was 63.5% and 54% at any time and at day 28 after basiliximab treatment. Grade III-IV aGVHD before basiliximab treatment predicted a poor ORR after basiliximab treatment. The rates of virus, bacteria, and fungi infections were 54%, 23.8%, and 3.1%, respectively. With a median follow-up of 730 (range, 67-3,042) days, the 1-year probability of overall survival and disease-free survival after basiliximab treatment were 58.6% (95% confidence interval [CI] = 47.6%-72.2%) and 55.4% (95% CI = 44.3%-69.2%), respectively. The 3-year cumulative incidence of relapse and non-relapse mortality after basiliximab treatment were 18.9% (95% CI = 8.3%-29.5%) and 33.8% (95% CI = 21.8%-45.7%), respectively. Comorbidities burden before allo-HSCT, severity of aGVHD and liver aGVHD before basiliximab treatment showed negative influences on survival. Thus, basiliximab was safe and effective treatment for SR-aGVHD following MSD-HSCT.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241257568"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11151754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141236693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}