{"title":"Anti-Inflammatory Effects of <i>Ex Vivo</i>-Generated Donor Antigen-Specific Immunomodulatory Cells on Pancreatic Islet Transplantation.","authors":"Agustina Forgioni, Masaaki Watanabe, Ryoichi Goto, Takuya Harada, Takuji Ota, Tsuyoshi Shimamura, Akinobu Taketomi","doi":"10.1177/09636897251317887","DOIUrl":"10.1177/09636897251317887","url":null,"abstract":"<p><p>Pancreatic islet transplantation (PITx) is a promising treatment option for patients with type 1 diabetes mellitus. Previously, we demonstrated that therapy with alloantigen-specific immunomodulatory cells (IMCs) generated <i>ex vivo</i> in the presence of anti-CD80 and CD86 monoclonal antibodies (mAbs), successfully induced tolerance following clinical liver transplantation. To extend IMC therapy to PITx, it is crucial to address the strong inflammatory and innate immune responses that occur immediately after PITx. In this study, we investigated the efficacy of IMCs in modulating macrophage activation and mitigating inflammatory damage of pancreatic islets. IMCs were induced using mouse splenocytes in the presence of anti-mouse anti-CD80 (RM80) and anti-CD86 (GL-1) mAbs. IMCs exerted donor-specific immunosuppressive effects in a mixed lymphocyte reaction. During lipopolysaccharide (LPS) stimulation, the addition of IMCs suppressed conversion to the M1 phenotype and promoted a shift toward the M2 phenotype, particularly under direct cell-cell contact conditions. Nitric oxide production, a hallmark of M1 polarized macrophages, was significantly reduced in LPS-stimulated RAW264 macrophages by IMC treatment. These findings were associated with reduced secretion of pro-inflammatory cytokines, tumoral necrosis factor α, and interleukin-6, and increased interleukin-10 production by macrophages. IMCs effectively prevented macrophage-mediated islet destruction after 12 h of co-culture with LPS-stimulated macrophages and significantly inhibited macrophage migration toward allogeneic islets <i>in vitro</i>. Intraportal co-infusion of IMCs with syngeneic islets in a mouse PITx model resulted in reduced messenger RNA (mRNA) expression of pro-inflammatory cytokines in the recipient liver. Immunohistochemical staining revealed a significantly lower number of F4/80+ macrophages at the transplantation site in IMCs-treated mice. These results demonstrate that IMCs modulate macrophage polarization, promoting a shift toward the M2 phenotype and protecting islets from macrophage-mediated damage. These effects combined with its intrinsic donor antigen-specific immunosuppressive capacity make IMC therapy a promising strategy for improving outcomes after PITx.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251317887"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467225","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}
Jayachandra Kuncha, Carly M Darden, Yang Liu, Michael Lawrence, J Sebastian Danobeitia, Bashoo Naziruddin
{"title":"Correlation of Pancreatic Laminin Alpha 5 Expression With Clinical Outcomes in Total Pancreatectomy With Islet Autotransplantation.","authors":"Jayachandra Kuncha, Carly M Darden, Yang Liu, Michael Lawrence, J Sebastian Danobeitia, Bashoo Naziruddin","doi":"10.1177/09636897251317048","DOIUrl":"10.1177/09636897251317048","url":null,"abstract":"<p><p>This study examines extracellular matrix (ECM) protein (ECM) expression in chronic pancreatitis (CP) patients and its correlation with graft function after total pancreatectomy with islet autologous transplantation (TPIAT). Pancreatic sections from 29 CP patients undergoing TPIAT were analyzed for ECM including pan-laminin, laminin alpha 5 (LAMA5), collagen IV, and Perlecan by immunohistochemistry and scored by the percentage positive staining area within the whole tissue area. Graft function was monitored by blood glucose and C-peptide levels. Laminin alpha 5 levels in blood plasma were greater in CP. Laminin alpha 5 expression was significantly higher in all CP patient etiological categories including alcoholic, hereditary, idiopathic, Oddi dysfunction, and pancreatic divisum compared to healthy controls. The overall expression of LAMA5 positively correlated with expression of the ECM proteins pan-laminin (<i>R</i> = 0.63, <i>P</i> < 0.001), collagen IV (<i>R</i> = 0.67, <i>P</i> < 0.001), and Perlecan (<i>R</i> = 0.71, <i>P</i> < 0.001). Increased LAMA5 expression was observed within islet endothelial vascular tissue and the peri-islet basal membrane. Increased LAMA5 expression in the pancreas correlated with poor islet isolation yield and posttransplant islet function after 3 months. Increased endothelial expression of LAMA5 and ECM proteins is indicative of progressive damage to the pancreas and correlates with poor graft function after TPIAT.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251317048"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490909","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":"Safe Administration of Immunosuppression in Japanese Monkeys: Relevance to Preclinical Xenotransplantation Studies.","authors":"Naoaki Sakata, Gumpei Yoshimatsu, Ryo Kawakami, Shohta Kodama","doi":"10.1177/09636897251322295","DOIUrl":"https://doi.org/10.1177/09636897251322295","url":null,"abstract":"<p><p>The Japanese monkey has been used in several animal studies; however, its potential as a recipient model for xenotransplantation is unclear. The potential of the Japanese monkey as a recipient for xenotransplantation was assessed using two experimental models. The first model evaluated the optimal dose of tacrolimus without severe adverse events. The plasma tacrolimus levels, blood counts, and hepatic and renal function tests were evaluated. The second model assessed the immunosuppressive effects of thymoglobulin and tacrolimus. Immunosuppression was evaluated using blood counts and flow cytometry to measure lymphocytes in peripheral blood mononuclear cells (PBMCs). In the first model, the target trough level (10-15 ng/ml) was achieved and maintained with tacrolimus administration at 1.6 mg/kg/day in all monkeys. There were no adverse events related to the blood count or to liver, kidney, or nutrient parameters at this dose, except for hemoglobin. In the second model, a decrease in white blood cells was observed. Flow cytometry revealed a temporary decrease in T- and B-cell numbers among PBMCs on day 4. We consider that the Japanese monkey is acceptable to be used as a recipient model for preclinical xenotransplantation. The safe administration of tacrolimus and thymoglobulin is clarified for this model.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251322295"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell TransplantationPub Date : 2025-01-01Epub Date: 2025-03-28DOI: 10.1177/09636897251325628
Liqing Jiang, Jie Wang, Yihua Wang, Hang Yang, Lingwang Kong, Zhongjun Wu, Ai Shen, ZuoTian Huang, Yingsong Jiang
{"title":"Bibliometric and LDA analysis of acute rejection in liver transplantation: Emerging trends, immunotherapy challenges, and the role of artificial intelligence.","authors":"Liqing Jiang, Jie Wang, Yihua Wang, Hang Yang, Lingwang Kong, Zhongjun Wu, Ai Shen, ZuoTian Huang, Yingsong Jiang","doi":"10.1177/09636897251325628","DOIUrl":"10.1177/09636897251325628","url":null,"abstract":"<p><p>With the rising demand for liver transplantation (LT), research on acute rejection (AR) has become increasingly diverse, yet no consensus has been reached. This study presents a bibliometric and latent Dirichlet allocation (LDA) topic modeling analysis of AR research in LT, encompassing 1399 articles. The United States, Zhejiang University, and the University of California, San Francisco emerged as leading contributors, while Levitsky J and Uemoto SJ were key researchers. The most influential journals included the <i>American Journal of Transplantation</i>, <i>Journal of Hepatology</i>, and <i>Transplantation</i>. The analysis reveals a transition from traditional histological assessments to molecular diagnostics, genetic and epigenetic profiling, and noninvasive biomarkers such as donor-derived cell-free DNA (dd-cfDNA) and microRNAs. Advances in immune checkpoint inhibitors (ICIs), cell-based therapies (Tregs, mesenchymal stem cells (MSCs)), AI-guided immunosuppression, and nanoparticle-mediated drug delivery systems reflect a growing emphasis on precision medicine. In addition, recent exploration of microbiome-based therapies and regenerative medicine, including MSCs and their extracellular vesicles, offers promising new avenues for reducing long-term immunosuppressive drug dependency and enhancing graft survival. These developments not only improve early AR detection and personalized treatment but also reduce toxicity, foster immune tolerance, and expand the scope of individualized therapeutic options. Global collaboration, supported by cutting-edge research and AI-driven decision-making, remains essential for refining AR strategies, improving graft survival, and achieving better long-term patient outcomes.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251325628"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728888","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}
Cell TransplantationPub Date : 2025-01-01Epub Date: 2025-03-28DOI: 10.1177/09636897251315271
Tetsuji Sekiya, Matthew C Holley
{"title":"The Glial Scar: To Penetrate or Not for Motor Pathway Restoration?","authors":"Tetsuji Sekiya, Matthew C Holley","doi":"10.1177/09636897251315271","DOIUrl":"10.1177/09636897251315271","url":null,"abstract":"<p><p>Although notable progress has been made, restoring motor function from the brain to the muscles continues to be a substantial clinical challenge in motor neuron diseases/disorders such as spinal cord injury (SCI). While cell transplantation has been widely explored as a potential therapeutic method for reconstructing functional motor pathways, there remains considerable opportunity for enhancing its therapeutic effectiveness. We reviewed studies on motor pathway regeneration to identify molecular and ultrastructural cues that could enhance the efficacy of cell transplantation. While the glial scar is often cited as an intractable barrier to axon regeneration, this mainly applies to axons trying to penetrate its \"core\" to reach the opposite side. However, the glial scar exhibits a \"duality,\" with an anti-regenerative core and a pro-regenerative \"surface.\" This surface permissiveness is attributed to pro-regenerative molecules, such as laminin in the basement membrane (BM). Transplanting donor cells onto the BM, which forms plastically after injury, may significantly enhance the efficacy of cell transplantation. Specifically, forming detour pathways between transplanted cells and endogenous propriospinal neurons on the pro-regenerative BM may efficiently bypass the intractable scar core and promote motor pathway regeneration. We believe harnessing the tissue's innate repair capacity is crucial, and targeting post-injury plasticity in astrocytes and Schwann cells, especially those associated with the BM that has predominantly been overlooked in the field of SCI research, can advance motor system restoration to a new stage. A shift in cell delivery routes-from the traditional intra-parenchymal (InP) route to the transplantation of donor cells onto the pro-regenerative BM via the extra-parenchymal (ExP) route-may signify a transformative step forward in neuro-regeneration research. Practically, however, the complementary use of both InP and ExP methods may offer the most substantial benefit for restoring motor pathways. We aim for this review to deepen the understanding of cell transplantation and provide a framework for evaluating the efficacy of this therapeutic modality in comparison to others.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251315271"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728890","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}
Cell TransplantationPub Date : 2025-01-01Epub Date: 2025-03-24DOI: 10.1177/09636897251323966
Rafael A Badell-Grau, Kasra Pakravesh, Kevin Eric Thai, Frankie Son, Rola Chen, Joseph Rainaldi, Kalvin Duong, Pauline Losay, Anusha Sivakumar, Veenita Khare, Alexis N Corl, Rushil Pithia, Christine Tran, Jefferey D Esko, Stephanie Cherqui
{"title":"Transplantation of Wild-Type Hematopoietic Stem and Progenitor Cells Improves Disease Phenotypes in a Mucopolysaccharidosis IIIC Mouse Model.","authors":"Rafael A Badell-Grau, Kasra Pakravesh, Kevin Eric Thai, Frankie Son, Rola Chen, Joseph Rainaldi, Kalvin Duong, Pauline Losay, Anusha Sivakumar, Veenita Khare, Alexis N Corl, Rushil Pithia, Christine Tran, Jefferey D Esko, Stephanie Cherqui","doi":"10.1177/09636897251323966","DOIUrl":"10.1177/09636897251323966","url":null,"abstract":"<p><p>Mucopolysaccharidosis type IIIC (MPS IIIC) is a severe neurodegenerative lysosomal storage disease caused by the loss-of-function of the lysosomal transmembrane protein acetyl-CoA: heparan-α-glucosamine <i>N</i>-acetyltransferase. MPS IIIC is characterized by the accumulation of the glycosaminoglycan (GAG) heparan sulfate. There is no treatment for this disease. We generated a new MPS IIIC mouse model and confirmed disease phenotypes such as GAG accumulation, splenomegaly, neurological defects, and presence of disease-specific non-reducing end carbohydrates. To explore a new therapeutic strategy for this condition, we transplanted wild-type (WT) hematopoietic stem and progenitor cells (HSPCs) into lethally irradiated 2-month-old <i>Hgsnat</i><sup>-/-</sup> mice and analyzed the resulting impact 6 months later. Transplanted HSPCs differentiated into macrophages in tissues and microglia-like cells in the brain. This resulted in a partial restoration of <i>Hgsnat</i> expression and enzymatic activity along with a significant reduction of the MPS IIIC-specific non-reducing end carbohydrate in the treated <i>Hgsnat</i><sup>-/-</sup> mice compared to untreated <i>Hgsnat</i><sup>-/-</sup> mice or <i>Hgsnat</i><sup>-/-</sup> mice transplanted with <i>Hgsnat</i><sup>-/-</sup> HPSCs. In addition, WT HSPC transplant resulted in improved neurological defects, reduction in splenomegaly, and urine retention in the <i>Hgsnat</i><sup>-/-</sup> mice. Furthermore, presence of glomerular hyaline bodies with focal fibrosis and sclerosis was observed in the kidney of the disease controls, whereas these abnormalities were improved in the <i>Hgsnat</i><sup>-/-</sup> mice treated with WT HSPCs. These data support that HSPC transplantation presents a promising therapeutic avenue for MPS IIIC and represents the first step toward the clinical translation of an HSPC-mediated therapy strategy for MPS IIIC.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251323966"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699669","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}
Guangyang Liu, Herui Wang, Chenliang Zhang, Xin Li, Yi Mi, Yaoyao Chen, Liqiang Xu, Li Miao, Haomiao Long, Yongjun Liu
{"title":"Tumor Necrosis Factor Receptor 1 Is Required for Human Umbilical Cord-Derived Mesenchymal Stem Cell-Mediated Rheumatoid Arthritis Therapy.","authors":"Guangyang Liu, Herui Wang, Chenliang Zhang, Xin Li, Yi Mi, Yaoyao Chen, Liqiang Xu, Li Miao, Haomiao Long, Yongjun Liu","doi":"10.1177/09636897241301703","DOIUrl":"10.1177/09636897241301703","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a systemic, chronic inflammatory disease characterized by altered levels of inflammatory cytokines. One of the key cytokines involved in the pathogenesis of RA is tumor necrosis factor α (TNF-α), which plays a crucial role in the differentiation of T cells and B cells and serves as a primary trigger of inflammation and joint damage in RA. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have shown potential in alleviating the symptoms of RA. Previous <i>in vitro</i> studies indicate that TNF-α secreted by T cells can activate NF-κB in human MSCs, thereby triggering the immunoregulatory capacity of MSCs in a manner dependent on tumor necrosis factor receptor 1 (TNFR1). Inspired by these findings, we aimed to evaluate whether TNFR1 determine the therapeutic effects of hUC-MSCs on RA. First, we investigated whether TNFR1 is necessary for hUC-MSCs to inhibit TNF-α production of PBMCs, a source of elevated TNF-α in patients. Through coculture experiment, we confirmed that this inhibition was dependent on TNFR1. Subsequently, we administered hUC-MSCs or siTNFR1-MSCs to DBA/1J male mice with collagen-induced arthritis. The results indicated that hUC-MSCs significantly alleviated the pathological features of RA and suppressed the inflammatory cytokines IFN-γ, TNF-α, and IL-6 in peripheral blood, also in a manner dependent on TNFR1 either. Given the dramatic pathologic differences between hUC-MSCs and siTNFR1-MSCs treatments, we questioned whether production of growth factors and chemokines was significantly influenced by TNFR1. Consequently, we stimulated hUC-MSCs or siTNFR1-MSCs through IFN-γ, TNF-α, and IL-6, and profiled growth factors and chemokines in serum, which revealed significant changes of hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF), as well as chemokines CXCL9, CXCL10, IL-8, and RANTES. In summary, our findings suggest that TNFR1 may determine whether hUC-MSCs will gain abilities of anti-inflammation and tissue regeneration.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897241301703"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001073","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}
Victoria Lövljung, Mathias Waldén, Mikael Sandell, Peter Damberg, Staffan Holmin, Fabian Arnberg Sandor
{"title":"Trans-Vessel Wall Cell Transplantation, Engraftment, and Tumor Access in the VX2 Rabbit Model.","authors":"Victoria Lövljung, Mathias Waldén, Mikael Sandell, Peter Damberg, Staffan Holmin, Fabian Arnberg Sandor","doi":"10.1177/09636897251313678","DOIUrl":"10.1177/09636897251313678","url":null,"abstract":"<p><p>The trans-vessel wall device (TW-device) is a new endovascular tool for precise and safe delivery of various payloads (cells, viral, modified RNA, chemotherapy, growth factors) in oncology and regenerative medicine. The twofold aim of this study was to assess cell engraftment and tumor growth using the TW-device for endovascular transplantation and to evaluate its ability to directly access solid tumors. We used the VX2 model in the rabbit kidney to compare percutaneously implanted fresh VX2 cells with TW-device injections of cryopreserved VX2 cells. We demonstrated the feasibility of endovascular transplantation (<i>n</i> = 7) of tumor cells, achieving a 57.1% engraftment rate despite cryopreservation, comparable with 70% for percutaneous delivery of fresh cells (<i>n</i> = 10). Re-access using the TW-device was 100% successful (<i>n</i> = 11) with super-selective intratumoral contrast administration without complications. In conclusion, endovascular transplantation of VX2 cells using the TW-device resulted in proliferating cell grafts in the rabbit kidney establishing functional proof that cells indeed survive handling, preparation, and device passage. We also show the TW-device is able to access solid tumor parenchyma allowing precise intraparenchymal administration.This proof-of-concept study open up possibilities for repeated direct parenchymal injections via the endovascular route in any hard to reach organ.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251313678"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051813","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}
Grisell C Gonzalez, Chris M Li, Ilaria Pasolini, Sophia I Pete, Connor Verheyen, Sofia M Vignolo, Teresa De Toni, Aaron A Stock, Alice A Tomei
{"title":"High-Yield Generation of Glucose-Responsive Pseudoislets From Murine Insulinoma Cells for <i>In Vitro</i> Studies and Longitudinal Monitoring of Graft Survival <i>In Vivo</i>.","authors":"Grisell C Gonzalez, Chris M Li, Ilaria Pasolini, Sophia I Pete, Connor Verheyen, Sofia M Vignolo, Teresa De Toni, Aaron A Stock, Alice A Tomei","doi":"10.1177/09636897251315123","DOIUrl":"10.1177/09636897251315123","url":null,"abstract":"<p><p>Compared to primary pancreatic islets, insulinoma cell-derived 3D pseudoislets offer a more accessible, consistent, renewable, and widely applicable model system for optimization and mechanistic studies in type 1 diabetes (T1D). Here, we report a simple and efficient method for generating 3D pseudoislets from MIN6 and NIT-1 murine insulinoma cells. These pseudoislets are homogeneous in size and morphology (~150 µm), exhibit functional glucose-stimulated insulin secretion (GSIS) up to 18 days (NIT-1) enabling long-term studies, are produced in high yield [>35,000 Islet Equivalence from 30 ml culture], and are suitable for both <i>in vitro</i> and <i>in vivo</i> studies, including for encapsulation studies. To enable non-invasive longitudinal monitoring of graft survival <i>in vivo</i>, we transduced NIT-1 cells with green fluorescent protein-luciferase and confirmed comparable morphology, viability, and GSIS to untransduced cells <i>in vitro</i>. After subcutaneous implantation, we show capability to monitor graft survival in immunodeficient mice, recurrence of autoimmunity in non-obese diabetic mice, and allorejection in C57BL/6 mice. Overall, this platform provides an accessible protocol for generating high yields of 3D pseudoislets and non-invasive longitudinal monitoring of graft survival in different models offer advantages over primary islets for optimization and mechanistic studies of β cell biology, drug discovery, T1D pathogenesis and prevention, and β cell transplantation.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251315123"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063969","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":"Robot-Assisted Stereotactic Microinjection Method for Precision Cell Transplantation in Rat and Canine Models.","authors":"Deqiang Han, Sichang Chen, Yuan Wang, Xueyao Wang, Xingzhe Wang, Tianqi Zheng, Zhiguo Chen","doi":"10.1177/09636897251323351","DOIUrl":"10.1177/09636897251323351","url":null,"abstract":"<p><p>Cell transplantation is a promising approach for addressing neurodegenerative conditions. In this study, we developed a robot-assisted stereotactic microinjection system for transplanting cells. We evaluated the factors that affect cellular graft viability and other properties, including the gauge of the syringe needle and the injection rate. We systematically compared the synchronous withdrawal injection (SWI) and fixed-point injection (FPI) procedures in agarose and rat brain models. <i>In vitro</i> assessments revealed superior dye dispersion with SWI compared to FPI, and <i>in vivo</i> analyses confirmed that SWI reduced the tissue injury and improved cell distribution in the striatum. We applied this robot-assisted technique to evaluate the accuracy and safety of cell transplantation in canine models. Overall, this strategy enhances the accuracy and safety of graft delivery, potentially improving outcomes and advancing therapeutic strategies for the clinical treatment of neurodegenerative disorders.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251323351"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656275","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}