Pedram Motallebnejad, Zion Lee, Jennifer L. One, Frank Cichocki, Wei‐Shou Hu, Samira M. Azarin
Natural killer (NK) cells are in development for allogeneic immunotherapy; however, for such use as off‐the‐shelf medicines, NK cells need to undergo ex vivo expansion, typically through activation with feeder cells and cytokines, to generate sufficient cells for clinical applications. Upon stimulation with feeder cells in the presence of cytokines, NK cells undergo profound changes in gene expression, altering their metabolic activity, cell cycle progression, and growth behavior, but the precise changes that drive this transformation remain poorly understood. In this study, we identified significant differences in the transcriptome and chromatin accessibility of NK cells 7 days after feeder cell and cytokine activation, with the changes even more pronounced in genome regions closer to enhancers. Several transcription factors, including AP‐1, IRF4, STATs, T‐bet, Eomes, and bHLHE40, which play key roles in NK cell development and immune response, exhibited differential binding activity between unstimulated and day 7 NK cells. Gene sets composed of target genes downstream of these transcription factors were also enriched at day 7, implying their involvement in NK cell activation. Moreover, we compared potential super‐enhancer regions in NK cells before and after activation, combined with the transcriptional activity of nearby genes. We identified stable and transcriptionally active super‐enhancers in unstimulated and day 7 NK cells, as well as those that form or disappear after co‐culture initiation. The transcriptomic and epigenetic characterization of NK cells presented in this study could facilitate the ex vivo expansion and engineering of functionally superior NK cells.
{"title":"Integrated ATAC‐seq and RNA‐seq analysis identifies key regulatory elements in NK cells activated with feeder cells and IL‐2","authors":"Pedram Motallebnejad, Zion Lee, Jennifer L. One, Frank Cichocki, Wei‐Shou Hu, Samira M. Azarin","doi":"10.1002/btm2.10747","DOIUrl":"https://doi.org/10.1002/btm2.10747","url":null,"abstract":"Natural killer (NK) cells are in development for allogeneic immunotherapy; however, for such use as off‐the‐shelf medicines, NK cells need to undergo ex vivo expansion, typically through activation with feeder cells and cytokines, to generate sufficient cells for clinical applications. Upon stimulation with feeder cells in the presence of cytokines, NK cells undergo profound changes in gene expression, altering their metabolic activity, cell cycle progression, and growth behavior, but the precise changes that drive this transformation remain poorly understood. In this study, we identified significant differences in the transcriptome and chromatin accessibility of NK cells 7 days after feeder cell and cytokine activation, with the changes even more pronounced in genome regions closer to enhancers. Several transcription factors, including AP‐1, IRF4, STATs, T‐bet, Eomes, and bHLHE40, which play key roles in NK cell development and immune response, exhibited differential binding activity between unstimulated and day 7 NK cells. Gene sets composed of target genes downstream of these transcription factors were also enriched at day 7, implying their involvement in NK cell activation. Moreover, we compared potential super‐enhancer regions in NK cells before and after activation, combined with the transcriptional activity of nearby genes. We identified stable and transcriptionally active super‐enhancers in unstimulated and day 7 NK cells, as well as those that form or disappear after co‐culture initiation. The transcriptomic and epigenetic characterization of NK cells presented in this study could facilitate the ex vivo expansion and engineering of functionally superior NK cells.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"7 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wan‐chen Tu, Ingrid H. Robertson, Andrea Blom, Elena Alfaro, Victoria A. M. Shinkawa, Daniel B. Hatchett, Juan C. Sanchez, Anika M. McManamen, Xiaojing Su, Erwin Berthier, Sanitta Thongpang, Ellen R. Wald, Gregory P. DeMuri, Ashleigh B. Theberge
State the PurposeObtaining high‐quality samples to diagnose streptococcal pharyngitis in pediatric patients is challenging due to discomfort associated with traditional pharyngeal swabs. This may cause reluctance to go to the clinic, inaccurate diagnosis, or inappropriate treatment for children with sore throats. Here, we determined the efficacy of CandyCollect, a lollipop‐inspired open‐microfluidic pathogen collection device, to capture Group A Streptococcus (GAS) and compare user preference for CandyCollect, conventional pharyngeal swabs, or mouth swabs in children with pharyngitis and their caregivers.ResultsAll child participants (30/30) were positive for GAS by qPCR on both the mouth swab and CandyCollect. Caregivers ranked CandyCollect as a good sampling method overall (27/30), and all caregivers (30/30) would recommend CandyCollect for children 5 years and older. Twenty‐three of 30 children “really like” the taste and 24/30 would prefer to use CandyCollect if a future test were needed. All caregivers (30/30) and most children (28/30) would be willing to use CandyCollect at home.ConclusionAll participants tested positive for GAS on all three collection methods (pharyngeal swab, mouth swab, and CandyCollect). While both caregivers and children like CandyCollect, some caregivers would prefer a shorter collection time. Future work includes additional studies with larger cohorts presenting with pharyngitis of unknown etiology and shortening collection time while maintaining the attractive form of the device.
{"title":"Capture of Group A Streptococcus by open‐microfluidic CandyCollect device in pediatric patients","authors":"Wan‐chen Tu, Ingrid H. Robertson, Andrea Blom, Elena Alfaro, Victoria A. M. Shinkawa, Daniel B. Hatchett, Juan C. Sanchez, Anika M. McManamen, Xiaojing Su, Erwin Berthier, Sanitta Thongpang, Ellen R. Wald, Gregory P. DeMuri, Ashleigh B. Theberge","doi":"10.1002/btm2.70001","DOIUrl":"https://doi.org/10.1002/btm2.70001","url":null,"abstract":"State the PurposeObtaining high‐quality samples to diagnose streptococcal pharyngitis in pediatric patients is challenging due to discomfort associated with traditional pharyngeal swabs. This may cause reluctance to go to the clinic, inaccurate diagnosis, or inappropriate treatment for children with sore throats. Here, we determined the efficacy of CandyCollect, a lollipop‐inspired open‐microfluidic pathogen collection device, to capture Group A <jats:italic>Streptococcus</jats:italic> (GAS) and compare user preference for CandyCollect, conventional pharyngeal swabs, or mouth swabs in children with pharyngitis and their caregivers.ResultsAll child participants (30/30) were positive for GAS by qPCR on both the mouth swab and CandyCollect. Caregivers ranked CandyCollect as a good sampling method overall (27/30), and all caregivers (30/30) would recommend CandyCollect for children 5 years and older. Twenty‐three of 30 children “really like” the taste and 24/30 would prefer to use CandyCollect if a future test were needed. All caregivers (30/30) and most children (28/30) would be willing to use CandyCollect at home.ConclusionAll participants tested positive for GAS on all three collection methods (pharyngeal swab, mouth swab, and CandyCollect). While both caregivers and children like CandyCollect, some caregivers would prefer a shorter collection time. Future work includes additional studies with larger cohorts presenting with pharyngitis of unknown etiology and shortening collection time while maintaining the attractive form of the device.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"6 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joana Lopes, Daniela Lopes, Mahzad Motallebi, Mengguang Ye, Yuxiang Xue, Amélia C. F. Vieira, Sachin Kumar Singh, Kamal Dua, Francisco Veiga, Gautam Sethi, Ana Cláudia Paiva‐Santos, Pooyan Makvandi
Gastrointestinal cancers, a major global cause of cancer‐related mortality and disease burden, are a heterogeneous group of malignant aliments involving different organs of the digestive system. The late clinical diagnosis, genomic tumor heterogeneity, high complexity of the gastrointestinal tumor microenvironment, along with increasing treatment resistance have been recognized as the main contributing factors to the current inadequacy of the clinical interventions and poor prognosis of the gastrointestinal cancer patients. In the coming years, gastrointestinal cancer‐related global mortality is unfortunately predicted to increase due to the absence of early detection and effective therapeutic options. Biomembrane‐coated biomimetic nanoparticles (NPs) have recently been appointed as advanced nanotechnological tools for the clinical management of gastrointestinal cancers. These comprise not only cell‐mimicking nanodevices (the pioneers of this top‐down coating technology), but also exosome and bacterial mimetics. Due to their enhanced bio‐interfacing features, biocompatibility, immune evasion, and specific targetability to tumorous tissues, these biomimetic nanostructures have been successfully exploited to provide safer, effective, and targeted gastrointestinal cancer applications. This review highlights the latest research on biomembrane‐coated nanosystems for the clinical therapy and diagnosis of the most common and deadliest subtypes of gastrointestinal cancers, namely colorectal cancer, gastric cancer, liver cancer, esophageal cancer, and pancreatic cancer. The current challenges toward their clinical translation are also mentioned.
{"title":"Biomembrane‐coated nanosystems as next‐generation delivery systems for the treatment of gastrointestinal cancers","authors":"Joana Lopes, Daniela Lopes, Mahzad Motallebi, Mengguang Ye, Yuxiang Xue, Amélia C. F. Vieira, Sachin Kumar Singh, Kamal Dua, Francisco Veiga, Gautam Sethi, Ana Cláudia Paiva‐Santos, Pooyan Makvandi","doi":"10.1002/btm2.70006","DOIUrl":"https://doi.org/10.1002/btm2.70006","url":null,"abstract":"Gastrointestinal cancers, a major global cause of cancer‐related mortality and disease burden, are a heterogeneous group of malignant aliments involving different organs of the digestive system. The late clinical diagnosis, genomic tumor heterogeneity, high complexity of the gastrointestinal tumor microenvironment, along with increasing treatment resistance have been recognized as the main contributing factors to the current inadequacy of the clinical interventions and poor prognosis of the gastrointestinal cancer patients. In the coming years, gastrointestinal cancer‐related global mortality is unfortunately predicted to increase due to the absence of early detection and effective therapeutic options. Biomembrane‐coated biomimetic nanoparticles (NPs) have recently been appointed as advanced nanotechnological tools for the clinical management of gastrointestinal cancers. These comprise not only cell‐mimicking nanodevices (the pioneers of this top‐down coating technology), but also exosome and bacterial mimetics. Due to their enhanced bio‐interfacing features, biocompatibility, immune evasion, and specific targetability to tumorous tissues, these biomimetic nanostructures have been successfully exploited to provide safer, effective, and targeted gastrointestinal cancer applications. This review highlights the latest research on biomembrane‐coated nanosystems for the clinical therapy and diagnosis of the most common and deadliest subtypes of gastrointestinal cancers, namely colorectal cancer, gastric cancer, liver cancer, esophageal cancer, and pancreatic cancer. The current challenges toward their clinical translation are also mentioned.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"37 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acute limb ischemia (ALI), especially acute lower limb ischemia (ALLI), is a common clinical vascular emergency with high amputation and mortality rates. However, major challenges exist in rapidly diagnosing and assessing collateral vascular compensatory capacity, leading to appropriate clinical treatment strategies to improve limb preservation and reduce recurrence rates. Traditional imaging methods, such as digital subtraction angiography (DSA) and ultrasound, have high demands on patient kidney function and operator maneuvers and are unable to monitor the temporal and spatial variability of collateral circulation establishment in the limb. In this study, we report the first combined use of real‐time and wide‐field laser speckle imaging (RFLSI), near‐infrared two‐zone imaging (NIR‐II), duplex ultrasound (DUS), and optical coherence tomography angiography (OCTA) for the diagnosis and monitoring of ALLI in male C57 and ICR mice. The RFLSI assesses overall perfusion, the NIR‐II allows rapid diagnosis and monitoring of the establishment of collateral circulation, DUS monitors muscle tenderness and stiffness, and OCTA detects microcirculation in the skin of the limb, which is confirmed by histopathological testing. Overall, the results of this study demonstrate the ability to accurately diagnose and detect ALLI with the help of a variety of optical and acoustic imaging devices, with significant clinical translational implications for intervention in clinical decision‐making preoperatively and prognostic assessment postoperatively.
{"title":"Noninvasive monitoring of vascular alterations in mice with acute lower limb ischemia using multimodal photoacoustic imaging","authors":"Heng Wang, Keyi Fan, Yijie Ning, Chuanlong Lu, Yuhang Zhang, Qian Wang, Hongjiu Zhang, Yaling Li, Zeyu Zhang, Xiaohua Jia, Sheng Yan, Ruijing Zhang, Honglin Dong","doi":"10.1002/btm2.70005","DOIUrl":"https://doi.org/10.1002/btm2.70005","url":null,"abstract":"Acute limb ischemia (ALI), especially acute lower limb ischemia (ALLI), is a common clinical vascular emergency with high amputation and mortality rates. However, major challenges exist in rapidly diagnosing and assessing collateral vascular compensatory capacity, leading to appropriate clinical treatment strategies to improve limb preservation and reduce recurrence rates. Traditional imaging methods, such as digital subtraction angiography (DSA) and ultrasound, have high demands on patient kidney function and operator maneuvers and are unable to monitor the temporal and spatial variability of collateral circulation establishment in the limb. In this study, we report the first combined use of real‐time and wide‐field laser speckle imaging (RFLSI), near‐infrared two‐zone imaging (NIR‐II), duplex ultrasound (DUS), and optical coherence tomography angiography (OCTA) for the diagnosis and monitoring of ALLI in male C57 and ICR mice. The RFLSI assesses overall perfusion, the NIR‐II allows rapid diagnosis and monitoring of the establishment of collateral circulation, DUS monitors muscle tenderness and stiffness, and OCTA detects microcirculation in the skin of the limb, which is confirmed by histopathological testing. Overall, the results of this study demonstrate the ability to accurately diagnose and detect ALLI with the help of a variety of optical and acoustic imaging devices, with significant clinical translational implications for intervention in clinical decision‐making preoperatively and prognostic assessment postoperatively.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"64 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143443419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dong‐Hyun Lee, You Bin Lee, Hyun Su Park, Young‐Ju Jang, Youn Chul Kim, Suk Ho Bhang
Adult human mesenchymal stem cells (hMSCs) injection into the wound site promotes angiogenesis and the wound‐closing process by secreting various growth and immune‐modulating factors. However, lower cell attachment sites and the hypoxic microenvironment in the wound site limit their viability and engraftment rate, leading to programmed cell death, anoikis. We synthesized carboxymethyl cellulose‐coated polylactic acid (CMC‐PLA) particles to prevent anoikis by providing an attachable surface for hMSCs. In vitro experiments demonstrated enhanced viability and secretion of growth factors by hMSCs under severely hypoxic microenvironments, when CMC‐PLA particles provided attachment surfaces, compared to controls. Furthermore, in vivo experiments showed that CMC‐PLA particles injected with hMSCs improved collagen synthesis and wound closure more than those of the control groups. These findings suggest that CMC‐PLA particles effectively enhance the therapeutic potential of hMSCs by providing a supportive microenvironment, promoting cell survival, proliferation, and angiogenesis, thereby offering a promising approach for advanced wound healing therapies.
{"title":"Carboxymethyl cellulose‐polylactic acid particles for inhibiting anoikis and enhancing wound healing efficacy of human mesenchymal stem cells","authors":"Dong‐Hyun Lee, You Bin Lee, Hyun Su Park, Young‐Ju Jang, Youn Chul Kim, Suk Ho Bhang","doi":"10.1002/btm2.70003","DOIUrl":"https://doi.org/10.1002/btm2.70003","url":null,"abstract":"Adult human mesenchymal stem cells (hMSCs) injection into the wound site promotes angiogenesis and the wound‐closing process by secreting various growth and immune‐modulating factors. However, lower cell attachment sites and the hypoxic microenvironment in the wound site limit their viability and engraftment rate, leading to programmed cell death, anoikis. We synthesized carboxymethyl cellulose‐coated polylactic acid (CMC‐PLA) particles to prevent anoikis by providing an attachable surface for hMSCs. In vitro experiments demonstrated enhanced viability and secretion of growth factors by hMSCs under severely hypoxic microenvironments, when CMC‐PLA particles provided attachment surfaces, compared to controls. Furthermore, in vivo experiments showed that CMC‐PLA particles injected with hMSCs improved collagen synthesis and wound closure more than those of the control groups. These findings suggest that CMC‐PLA particles effectively enhance the therapeutic potential of hMSCs by providing a supportive microenvironment, promoting cell survival, proliferation, and angiogenesis, thereby offering a promising approach for advanced wound healing therapies.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"5 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The detection and complete eradication of early‐stage small tumors during hysteroscopy remains a significant clinical challenge in preserving fertility for young women with endometrial cancer (EC). The purpose of this study is to verify the feasibility of CD47 as an optical molecular imaging (OMI) target for human EC and to achieve precise localization and identification in hysteroscopic surgery. The results demonstrated that CD47 was overexpressed in EC through bioinformatics, immunohistochemistry, and qRT‐PCR. In EC cell lines, CD47‐targeted near‐infrared photoimmunotherapy (NIR‐PIT) induced cytotoxicity in a light dose‐dependent manner. Laser confocal microscopy revealed that CD47 intervention significantly increased the phagocytic effect of macrophages on EC cells. In the mice model of partial tumor resection mediated by CD47‐targeted OMI, compared to group A (immune therapy alone), group C (NIR‐PIT treatment) mice showed a reduced tumor recurrence rate after NIR‐PIT intervention. However, the difference did not reach statistical significance. We then evaluated the effect of CD47‐targeted NIR‐PIT maintenance therapy on tumor recurrence in mice. The results indicated that, compared to untreated animals, the tumor growth rate was slower in the NIR‐PIT group using CD47‐Alexa Fluor 790 (CD47‐AF790), allowing for more sustained tumor control. The freshly isolated whole uterus specimens from EC patients were co‐incubated with CD47‐AF790, and a significantly enhanced contrast of NIR visible images of tumor tissue was observed, demonstrating high sensitivity and specificity (tumor‐to‐background ratio >5.05). Finally, under fluorescence microscopy, specific fluorescent signals are observed on tumor cells. In conclusion, accurate localization and excision of EC can be accomplished by employing CD47 optical molecular contrast agents with OMI technology. This method shows potential as a viable and promising approach for the precise diagnosis of EC.
{"title":"Multimodal near‐infrared molecular imaging of ex vivo endometrial carcinoma via CD47‐based targeted tracer","authors":"Jing Lei, Dianfeng Tian, Bo Zhang, Hongrui Guo, Huancheng Su, Jinzheng Wei, Shuai Li, Sufen Li, Chao Liu, Xiaofeng Yang, Sanyuan Zhang","doi":"10.1002/btm2.10754","DOIUrl":"https://doi.org/10.1002/btm2.10754","url":null,"abstract":"The detection and complete eradication of early‐stage small tumors during hysteroscopy remains a significant clinical challenge in preserving fertility for young women with endometrial cancer (EC). The purpose of this study is to verify the feasibility of CD47 as an optical molecular imaging (OMI) target for human EC and to achieve precise localization and identification in hysteroscopic surgery. The results demonstrated that CD47 was overexpressed in EC through bioinformatics, immunohistochemistry, and qRT‐PCR. In EC cell lines, CD47‐targeted near‐infrared photoimmunotherapy (NIR‐PIT) induced cytotoxicity in a light dose‐dependent manner. Laser confocal microscopy revealed that CD47 intervention significantly increased the phagocytic effect of macrophages on EC cells. In the mice model of partial tumor resection mediated by CD47‐targeted OMI, compared to group A (immune therapy alone), group C (NIR‐PIT treatment) mice showed a reduced tumor recurrence rate after NIR‐PIT intervention. However, the difference did not reach statistical significance. We then evaluated the effect of CD47‐targeted NIR‐PIT maintenance therapy on tumor recurrence in mice. The results indicated that, compared to untreated animals, the tumor growth rate was slower in the NIR‐PIT group using CD47‐Alexa Fluor 790 (CD47‐AF790), allowing for more sustained tumor control. The freshly isolated whole uterus specimens from EC patients were co‐incubated with CD47‐AF790, and a significantly enhanced contrast of NIR visible images of tumor tissue was observed, demonstrating high sensitivity and specificity (tumor‐to‐background ratio >5.05). Finally, under fluorescence microscopy, specific fluorescent signals are observed on tumor cells. In conclusion, accurate localization and excision of EC can be accomplished by employing CD47 optical molecular contrast agents with OMI technology. This method shows potential as a viable and promising approach for the precise diagnosis of EC.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"25 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143125138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tiffany Rui Xuan Gan, Lester W. J. Tan, Mathias Egermark, Anh T. L. Truong, Kirthika Kumar, Shi‐Bei Tan, Sarah Tang, Agata Blasiak, Boon Cher Goh, Kee Yuan Ngiam, Dean Ho
BackgroundStandard‐of‐care for warfarin dose titration is conventionally based on physician‐guided drug dosing. This may lead to frequent deviations from target international normalized ratio (INR) due to inter‐ and intra‐patient variability and may potentially result in adverse events including recurrent thromboembolism and life‐threatening hemorrhage.ObjectivesWe aim to employ CURATE.AI, a small‐data, artificial intelligence‐derived platform that has been clinically validated in a range of indications, to optimize and guide warfarin dosing.Patients/methodsA personalized CURATE.AI response profile was generated using warfarin dose (inputs) and corresponding change in INR between two consecutive days (phenotypic outputs) and used to identify and recommend an optimal dose to achieve target treatment outcomes. CURATE.AI's predictive performance was then evaluated with a set of metrics that assessed both technical performance and clinical relevance.Results and conclusionsIn this retrospective study of 127 patients, CURATE.AI fared better in terms of Percentage Absolute Prediction Error and Percentage Prediction Error of 20% compared to other models in the literature. It also had negligible underprediction bias, potentially translating into lower bleeding risk. Modeled potential time in therapeutic range with CURATE.AI was not significantly different from physician‐guided dosing, so it is on‐par yet provides a systematic approach to warfarin dosing, easing the mental‐burden on guesswork by physicians.This study lays the groundwork for the prospective study of CURATE.AI as a clinical decision support system. CURATE.AI may facilitate the effective use of affordable warfarin with a well‐established safety profile, without the need for costly, new oral anticoagulants. This can have significant impact both on the individual and public health.
{"title":"AI‐assisted warfarin dose optimisation with CURATE.AI for clinical impact: Retrospective data analysis","authors":"Tiffany Rui Xuan Gan, Lester W. J. Tan, Mathias Egermark, Anh T. L. Truong, Kirthika Kumar, Shi‐Bei Tan, Sarah Tang, Agata Blasiak, Boon Cher Goh, Kee Yuan Ngiam, Dean Ho","doi":"10.1002/btm2.10757","DOIUrl":"https://doi.org/10.1002/btm2.10757","url":null,"abstract":"BackgroundStandard‐of‐care for warfarin dose titration is conventionally based on physician‐guided drug dosing. This may lead to frequent deviations from target international normalized ratio (INR) due to inter‐ and intra‐patient variability and may potentially result in adverse events including recurrent thromboembolism and life‐threatening hemorrhage.ObjectivesWe aim to employ CURATE.AI, a small‐data, artificial intelligence‐derived platform that has been clinically validated in a range of indications, to optimize and guide warfarin dosing.Patients/methodsA personalized CURATE.AI response profile was generated using warfarin dose (inputs) and corresponding change in INR between two consecutive days (phenotypic outputs) and used to identify and recommend an optimal dose to achieve target treatment outcomes. CURATE.AI's predictive performance was then evaluated with a set of metrics that assessed both technical performance and clinical relevance.Results and conclusionsIn this retrospective study of 127 patients, CURATE.AI fared better in terms of Percentage Absolute Prediction Error and Percentage Prediction Error of 20% compared to other models in the literature. It also had negligible underprediction bias, potentially translating into lower bleeding risk. Modeled potential time in therapeutic range with CURATE.AI was not significantly different from physician‐guided dosing, so it is on‐par yet provides a systematic approach to warfarin dosing, easing the mental‐burden on guesswork by physicians.This study lays the groundwork for the prospective study of CURATE.AI as a clinical decision support system. CURATE.AI may facilitate the effective use of affordable warfarin with a well‐established safety profile, without the need for costly, new oral anticoagulants. This can have significant impact both on the individual and public health.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"39 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem cell therapies have emerged as a transformative approach in modern medicine, with the potential to address and possibly cure a broad spectrum of diseases. These therapies utilize living stem cells that can perform complex biological functions not replicable by traditional drugs. Stem cell therapies have an expanding therapeutic landscape, with several products already approved and numerous clinical trials underway. Among the various stem cell types, hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) are most widely studied. In this review, we provide a detailed analysis of the current clinical landscape of stem cell therapies. We review 27 stem cell products that have received regulatory approvals and discuss 800 ongoing clinical trials, with a focus on HSCs and MSCs. We also discuss the critical challenges to be addressed to facilitate the clinical translation of stem cell therapies.
{"title":"Stem cell therapies in the clinic","authors":"Shrinivas Acharya, Suyog Shaha, Michael Griffith Bibbey, Malini Mukherji, Zongmin Zhao, Samir Mitragotri","doi":"10.1002/btm2.70000","DOIUrl":"https://doi.org/10.1002/btm2.70000","url":null,"abstract":"Stem cell therapies have emerged as a transformative approach in modern medicine, with the potential to address and possibly cure a broad spectrum of diseases. These therapies utilize living stem cells that can perform complex biological functions not replicable by traditional drugs. Stem cell therapies have an expanding therapeutic landscape, with several products already approved and numerous clinical trials underway. Among the various stem cell types, hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) are most widely studied. In this review, we provide a detailed analysis of the current clinical landscape of stem cell therapies. We review 27 stem cell products that have received regulatory approvals and discuss 800 ongoing clinical trials, with a focus on HSCs and MSCs. We also discuss the critical challenges to be addressed to facilitate the clinical translation of stem cell therapies.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"26 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143125137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cardiovascular diseases (CVDs) continue to drive global mortality rates, underscoring an urgent need for advancements in healthcare solutions. The development of point‐of‐care (POC) devices that provide rapid diagnostic services near patients has garnered substantial attention, especially as traditional healthcare systems face challenges such as delayed diagnoses, inadequate care, and rising medical costs. The advancement of machine learning techniques has sparked considerable interest in medical research and engineering, offering ways to enhance diagnostic accuracy and relevance. Improved data interoperability and seamless connectivity could enable real‐time, continuous monitoring of cardiovascular health. Recent breakthroughs in computing power and algorithmic design, particularly deep learning frameworks that emulate neural processes, have revolutionized POC devices for CVDs, enabling more frequent detection of abnormalities and automated, expert‐level diagnosis. However, challenges such as data privacy concerns and biases in dataset representation continue to hinder clinical integration. Despite these barriers, the translational potential of machine learning‐assisted POC devices presents significant opportunities for advancement in CVDs healthcare.
{"title":"Machine learning‐assisted point‐of‐care diagnostics for cardiovascular healthcare","authors":"Kaidong Wang, Bing Tan, Xinfei Wang, Shicheng Qiu, Qiuping Zhang, Shaolei Wang, Ying‐Tzu Yen, Nan Jing, Changming Liu, Xuxu Chen, Shichang Liu, Yan Yu","doi":"10.1002/btm2.70002","DOIUrl":"https://doi.org/10.1002/btm2.70002","url":null,"abstract":"Cardiovascular diseases (CVDs) continue to drive global mortality rates, underscoring an urgent need for advancements in healthcare solutions. The development of point‐of‐care (POC) devices that provide rapid diagnostic services near patients has garnered substantial attention, especially as traditional healthcare systems face challenges such as delayed diagnoses, inadequate care, and rising medical costs. The advancement of machine learning techniques has sparked considerable interest in medical research and engineering, offering ways to enhance diagnostic accuracy and relevance. Improved data interoperability and seamless connectivity could enable real‐time, continuous monitoring of cardiovascular health. Recent breakthroughs in computing power and algorithmic design, particularly deep learning frameworks that emulate neural processes, have revolutionized POC devices for CVDs, enabling more frequent detection of abnormalities and automated, expert‐level diagnosis. However, challenges such as data privacy concerns and biases in dataset representation continue to hinder clinical integration. Despite these barriers, the translational potential of machine learning‐assisted POC devices presents significant opportunities for advancement in CVDs healthcare.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"25 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tiffany Hood, Pierre Springuel, Fern Slingsby, Viktor Sandner, Winfried Geis, Timo Schmidberger, Nicola Bevan, Quentin Vicard, Julia Hengst, Noushin Dianat, Qasim A. Rafiq
Chimeric antigen receptor T cell (CAR‐T) therapies show high remission rates for relapsed and refractory leukemia and lymphoma. However, manufacturing challenges hinder their commercial viability and patient accessibility. This study applied quality‐by‐design principles to identify perfusion critical process parameters for CAR‐T expansion in stirred tank bioreactors to maximize yields. A design of experiments in the Ambr® 250 High Throughput Perfusion small‐scale bioreactor revealed that earlier perfusion starts (48 h vs. 96 h post‐inoculation) and higher perfusion rates (1.0 VVD vs. 0.25 VVD) significantly increased cytotoxic CAR‐T cell yields without compromising critical quality attributes. Optimizing perfusion improved growth kinetics and yields across donor samples, achieving densities >21 × 106 cells/mL in 7 days, outperforming traditional fed‐batch and static flask cultures. This study underscores the importance of optimizing perfusion parameters to maximize CAR‐T yields and quality and highlights the utility of scale‐down models in reducing time, costs and risks associated with process development.
{"title":"Establishing a scalable perfusion strategy for the manufacture of CAR‐T cells in stirred‐tank bioreactors using a quality‐by‐design approach","authors":"Tiffany Hood, Pierre Springuel, Fern Slingsby, Viktor Sandner, Winfried Geis, Timo Schmidberger, Nicola Bevan, Quentin Vicard, Julia Hengst, Noushin Dianat, Qasim A. Rafiq","doi":"10.1002/btm2.10753","DOIUrl":"https://doi.org/10.1002/btm2.10753","url":null,"abstract":"Chimeric antigen receptor T cell (CAR‐T) therapies show high remission rates for relapsed and refractory leukemia and lymphoma. However, manufacturing challenges hinder their commercial viability and patient accessibility. This study applied quality‐by‐design principles to identify perfusion critical process parameters for CAR‐T expansion in stirred tank bioreactors to maximize yields. A design of experiments in the Ambr® 250 High Throughput Perfusion small‐scale bioreactor revealed that earlier perfusion starts (48 h vs. 96 h post‐inoculation) and higher perfusion rates (1.0 VVD vs. 0.25 VVD) significantly increased cytotoxic CAR‐T cell yields without compromising critical quality attributes. Optimizing perfusion improved growth kinetics and yields across donor samples, achieving densities >21 × 10<jats:sup>6</jats:sup> cells/mL in 7 days, outperforming traditional fed‐batch and static flask cultures. This study underscores the importance of optimizing perfusion parameters to maximize CAR‐T yields and quality and highlights the utility of scale‐down models in reducing time, costs and risks associated with process development.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"49 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：