Pearlson Prashanth Austin Suthanthiraraj, Sydney Bone, Kyung‐Ho Roh
As the prospect of engineering primary B‐cells for cellular therapies in cancer, autoimmune diseases, and infectious diseases grows, there is an increasing demand for robust in vitro culture systems that effectively activate human B‐cells isolated from peripheral blood for consistent and efficient expansion and differentiation into various effector phenotypes. Feeder cell‐based systems have shown promise in providing long‐term signaling for expanding B‐cells in vitro. However, these co‐culture systems necessitate more rigorous downstream processing to prevent various feeder cell‐related contaminations in the final product, which limits their clinical potential. In this study, we introduce a microbead‐based CD40L‐presentation platform for stable and consistent activation of human naïve B‐cells. By employing a completely synthetic in vitro culture approach integrating B‐cell receptor, CD21 co‐receptor, toll‐like receptor (TLR‐9), and cytokine signals, we demonstrate that naïve B‐cells can differentiate into memory B‐cells (IgD‐CD38‐/lo + CD27+) and antibody‐secreting cells (IgD‐CD38++CD27+). During this process, B‐cells underwent up to a 50‐fold expansion, accompanied by isotype class switching and low levels of somatic hypermutation, mimicking physiological events within the germinal center. The reproducible generation of highly expanded and differentiated effector B‐cells from naïve B‐cells of multiple donors positions this feeder‐free in vitro synthetic niche as a promising platform for large‐scale production of effector B‐cell therapeutics.
{"title":"Microbead‐based synthetic niches for in vitro expansion and differentiation of human naïve B‐cells","authors":"Pearlson Prashanth Austin Suthanthiraraj, Sydney Bone, Kyung‐Ho Roh","doi":"10.1002/btm2.10751","DOIUrl":"https://doi.org/10.1002/btm2.10751","url":null,"abstract":"As the prospect of engineering primary B‐cells for cellular therapies in cancer, autoimmune diseases, and infectious diseases grows, there is an increasing demand for robust in vitro culture systems that effectively activate human B‐cells isolated from peripheral blood for consistent and efficient expansion and differentiation into various effector phenotypes. Feeder cell‐based systems have shown promise in providing long‐term signaling for expanding B‐cells in vitro. However, these co‐culture systems necessitate more rigorous downstream processing to prevent various feeder cell‐related contaminations in the final product, which limits their clinical potential. In this study, we introduce a microbead‐based CD40L‐presentation platform for stable and consistent activation of human naïve B‐cells. By employing a completely synthetic in vitro culture approach integrating B‐cell receptor, CD21 co‐receptor, toll‐like receptor (TLR‐9), and cytokine signals, we demonstrate that naïve B‐cells can differentiate into memory B‐cells (IgD‐CD38‐/lo + CD27+) and antibody‐secreting cells (IgD‐CD38++CD27+). During this process, B‐cells underwent up to a 50‐fold expansion, accompanied by isotype class switching and low levels of somatic hypermutation, mimicking physiological events within the germinal center. The reproducible generation of highly expanded and differentiated effector B‐cells from naïve B‐cells of multiple donors positions this feeder‐free in vitro synthetic niche as a promising platform for large‐scale production of effector B‐cell therapeutics.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"7 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988889","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}
Ziyan An, Pengchao Wang, Zhengyun Ling, Kaipeng Bi, Zheng Wang, Jinpeng Shao, Jian Zhao, Zhouyang Fu, Meng Huang, Wenjie Wei, Shuwei Xiao, Jin Zhou, Weijun Fu
Previous studies of bladder tissue engineering simply seeded cells onto the surface of the material, which makes the cells lack protection and makes it difficult to face the complex in vivo environment. The gelatin methacryloyl (GelMA) hydrogel possesses outstanding biocompatibility and distinctive photo‐crosslinking characteristics and is capable of offering a suitable three‐dimensional growth environment for cells. This study explored the optimal concentration of GelMA for encapsulating adipose‐derived stem cells (ADSCs) and combined it with bladder acellular matrix (BAM) to create a tissue‐engineered bladder patch. Results indicated that 10% GelMA more effectively promoted ADSCs proliferation and spreading compared to 7.5% and 12.5% concentrations, which can offer a better extracellular matrix environment for cells. BAM performed as an excellent substrate with mechanical properties and stitchability similar to natural tissues. Animal experiments demonstrated that the encapsulated ADSCs in GelMA enhanced patch vascularization in vivo and BAM‐GelMA‐ADSCs tissue‐engineered bladder patch can repair large‐scale bladder defects in beagles and promote bladder tissue regeneration and functional recovery. This photocrosslinking hydrogel‐acellular matrix patch provides a protective semi‐controlled environment for ADSCs, supporting the growth and viability of encapsulated cells in vivo, while being easy to suture and preventing leakage, and has significant clinical potential.
{"title":"The BAM‐GelMA‐ADSCs bilayer patch promotes tissue regeneration and functional recovery after large‐area bladder defects in beagles","authors":"Ziyan An, Pengchao Wang, Zhengyun Ling, Kaipeng Bi, Zheng Wang, Jinpeng Shao, Jian Zhao, Zhouyang Fu, Meng Huang, Wenjie Wei, Shuwei Xiao, Jin Zhou, Weijun Fu","doi":"10.1002/btm2.10745","DOIUrl":"https://doi.org/10.1002/btm2.10745","url":null,"abstract":"Previous studies of bladder tissue engineering simply seeded cells onto the surface of the material, which makes the cells lack protection and makes it difficult to face the complex in vivo environment. The gelatin methacryloyl (GelMA) hydrogel possesses outstanding biocompatibility and distinctive photo‐crosslinking characteristics and is capable of offering a suitable three‐dimensional growth environment for cells. This study explored the optimal concentration of GelMA for encapsulating adipose‐derived stem cells (ADSCs) and combined it with bladder acellular matrix (BAM) to create a tissue‐engineered bladder patch. Results indicated that 10% GelMA more effectively promoted ADSCs proliferation and spreading compared to 7.5% and 12.5% concentrations, which can offer a better extracellular matrix environment for cells. BAM performed as an excellent substrate with mechanical properties and stitchability similar to natural tissues. Animal experiments demonstrated that the encapsulated ADSCs in GelMA enhanced patch vascularization in vivo and BAM‐GelMA‐ADSCs tissue‐engineered bladder patch can repair large‐scale bladder defects in beagles and promote bladder tissue regeneration and functional recovery. This photocrosslinking hydrogel‐acellular matrix patch provides a protective semi‐controlled environment for ADSCs, supporting the growth and viability of encapsulated cells in vivo, while being easy to suture and preventing leakage, and has significant clinical potential.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"23 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986004","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}
Hoi Y. Kwon, Christopher Streilein, R. Chase Cornelison
Spinal cord injury (SCI) initiates a complex cascade of chemical and biophysical phenomena that result in tissue swelling, progressive neural degeneration, and formation of a fluid‐filled cavity. Previous studies show fluid pressure above the spinal cord (supraspinal) is elevated for at least 3 days after injury and contributes to a phase of damage called secondary injury. Currently, it is unknown how fluid forces within the spinal cord itself (interstitial) are affected by SCI and if they contribute to secondary injury. We find spinal interstitial pressure increases from −3 mmHg in the naive cord to a peak of 13 mmHg at 3 days post‐injury (DPI) but relatively normalizes to 2 mmHg by 7 DPI. A computational fluid dynamics model predicts interstitial flow velocities up to 0.9 μm/s at 3 DPI, returning to near baseline by 7 DPI. By quantifying vascular leakage of Evans Blue dye after a cervical hemi‐contusion in rats, we confirm an increase in dye infiltration at 3 DPI compared to 7 DPI, suggestive of higher fluid velocities at the time of peak fluid pressure. In vivo expression of the apoptosis marker caspase‐3 is strongly correlated with regions of interstitial flow at 3 DPI, and exogenously enhancing interstitial flow exacerbates tissue damage. In vitro, we show overnight exposure of neuronal cells to low pathological shear stress (0.1 dynes/cm2) significantly reduces cell count and neurite length. Collectively, these results indicate that interstitial fluid flow and shear stress may play a detrimental role in post‐traumatic neural degeneration.
{"title":"Convective forces contribute to post‐traumatic degeneration after spinal cord injury","authors":"Hoi Y. Kwon, Christopher Streilein, R. Chase Cornelison","doi":"10.1002/btm2.10739","DOIUrl":"https://doi.org/10.1002/btm2.10739","url":null,"abstract":"Spinal cord injury (SCI) initiates a complex cascade of chemical and biophysical phenomena that result in tissue swelling, progressive neural degeneration, and formation of a fluid‐filled cavity. Previous studies show fluid pressure above the spinal cord (supraspinal) is elevated for at least 3 days after injury and contributes to a phase of damage called secondary injury. Currently, it is unknown how fluid forces within the spinal cord itself (interstitial) are affected by SCI and if they contribute to secondary injury. We find spinal interstitial pressure increases from −3 mmHg in the naive cord to a peak of 13 mmHg at 3 days post‐injury (DPI) but relatively normalizes to 2 mmHg by 7 DPI. A computational fluid dynamics model predicts interstitial flow velocities up to 0.9 μm/s at 3 DPI, returning to near baseline by 7 DPI. By quantifying vascular leakage of Evans Blue dye after a cervical hemi‐contusion in rats, we confirm an increase in dye infiltration at 3 DPI compared to 7 DPI, suggestive of higher fluid velocities at the time of peak fluid pressure. In vivo expression of the apoptosis marker caspase‐3 is strongly correlated with regions of interstitial flow at 3 DPI, and exogenously enhancing interstitial flow exacerbates tissue damage. In vitro, we show overnight exposure of neuronal cells to low pathological shear stress (0.1 dynes/cm<jats:sup>2</jats:sup>) significantly reduces cell count and neurite length. Collectively, these results indicate that interstitial fluid flow and shear stress may play a detrimental role in post‐traumatic neural degeneration.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"52 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981182","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}
This comprehensive review explores the implications of artificial intelligence (AI) in addressing cochlear implant (CI) issues and revolutionizing the landscape of auditory prosthetics. It begins with an overview of ear anatomy and hearing loss, then explores a review of CI technology and its current challenges. The review emphasizes how advanced AI algorithms and data‐driven approaches enhance CI adaptability and functionality, enabling personalized rehabilitation strategies and improving speech enhancement. It highlights diverse AI applications in auditory rehabilitation, including real‐time adaptive control mechanisms and cognitive hearing assistants that help users manage their auditory health. By outlining innovative pathways and future directions for AI‐enhanced CIs, the paper sets the stage for a transformative shift in auditory prosthetics, aiming to improve the quality of life for individuals with hearing loss.
{"title":"Artificial intelligence‐enabled innovations in cochlear implant technology: Advancing auditory prosthetics for hearing restoration","authors":"Guodao Zhang, Rui Chen, Hamzeh Ghorbani, Wanqing Li, Arsen Minasyan, Yideng Huang, Sen Lin, Minmin Shao","doi":"10.1002/btm2.10752","DOIUrl":"https://doi.org/10.1002/btm2.10752","url":null,"abstract":"This comprehensive review explores the implications of artificial intelligence (AI) in addressing cochlear implant (CI) issues and revolutionizing the landscape of auditory prosthetics. It begins with an overview of ear anatomy and hearing loss, then explores a review of CI technology and its current challenges. The review emphasizes how advanced AI algorithms and data‐driven approaches enhance CI adaptability and functionality, enabling personalized rehabilitation strategies and improving speech enhancement. It highlights diverse AI applications in auditory rehabilitation, including real‐time adaptive control mechanisms and cognitive hearing assistants that help users manage their auditory health. By outlining innovative pathways and future directions for AI‐enhanced CIs, the paper sets the stage for a transformative shift in auditory prosthetics, aiming to improve the quality of life for individuals with hearing loss.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"129 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961440","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}
Emily H. Powsner, Stephanie M. Kronstadt, Kristin Nikolov, Amaya Aranda, Steven M. Jay
Mesenchymal stem cell‐derived extracellular vesicles (MSC EVs) are an attractive therapeutic option for regenerative medicine applications due to their inherently pro‐angiogenic and anti‐inflammatory properties. However, reproducible and cost‐effective production of highly potent therapeutic MSC EVs is challenging, limiting their translational potential. Here, we investigated whether the well‐characterized responsiveness of MSCs to their mechanical environment—specifically, substrate stiffness—could be exploited to generate EVs with increased therapeutic bioactivity without the need for biochemical priming or genetic manipulation. Using polydimethylsiloxane and bone marrow‐derived MSCs (BM‐MSCs), we show that decreasing the stiffness of MSC substrates to as low as 3 kPa significantly improves the pro‐angiogenic bioactivity of EVs as measured by tube formation and gap closure assays. We also demonstrate that lower substrate stiffness improves EV production and overall yield, important for clinical translation. Furthermore, we establish the mechanoresponsiveness of induced pluripotent stem cell‐derived MSC (iMSC) EVs and their comparability to BM‐MSC EVs, again using tube formation and gap closure assays. With this data, we confirm iMSCs' feasibility as an alternative, renewable cell source for EV production with reduced donor variability. Overall, these results suggest that utilizing substrate stiffness is a promising, simple, and a potentially scalable approach that does not require exogenous cargo or extraneous reagents to generate highly potent pro‐angiogenic MSC EVs.
{"title":"Mesenchymal stem cell extracellular vesicle vascularization bioactivity and production yield are responsive to cell culture substrate stiffness","authors":"Emily H. Powsner, Stephanie M. Kronstadt, Kristin Nikolov, Amaya Aranda, Steven M. Jay","doi":"10.1002/btm2.10743","DOIUrl":"https://doi.org/10.1002/btm2.10743","url":null,"abstract":"Mesenchymal stem cell‐derived extracellular vesicles (MSC EVs) are an attractive therapeutic option for regenerative medicine applications due to their inherently pro‐angiogenic and anti‐inflammatory properties. However, reproducible and cost‐effective production of highly potent therapeutic MSC EVs is challenging, limiting their translational potential. Here, we investigated whether the well‐characterized responsiveness of MSCs to their mechanical environment—specifically, substrate stiffness—could be exploited to generate EVs with increased therapeutic bioactivity without the need for biochemical priming or genetic manipulation. Using polydimethylsiloxane and bone marrow‐derived MSCs (BM‐MSCs), we show that decreasing the stiffness of MSC substrates to as low as 3 kPa significantly improves the pro‐angiogenic bioactivity of EVs as measured by tube formation and gap closure assays. We also demonstrate that lower substrate stiffness improves EV production and overall yield, important for clinical translation. Furthermore, we establish the mechanoresponsiveness of induced pluripotent stem cell‐derived MSC (iMSC) EVs and their comparability to BM‐MSC EVs, again using tube formation and gap closure assays. With this data, we confirm iMSCs' feasibility as an alternative, renewable cell source for EV production with reduced donor variability. Overall, these results suggest that utilizing substrate stiffness is a promising, simple, and a potentially scalable approach that does not require exogenous cargo or extraneous reagents to generate highly potent pro‐angiogenic MSC EVs.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"5 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142935713","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}
Grace E. Olsson, Rohan V. Patil, Samantha J. Chin, Katharine N. Rus, Elizabeth E. Sweeney, Karun V. Sharma, Rohan Fernandes
We describe the use of ultrasound image guidance to improve treatment outcomes when administering interstitial photothermal therapy (I‐PTT), an experimental cancer treatment modality. I‐PTT is a promising thermal therapy for tumors using intratumorally injected nanoparticle‐based photothermal agents activated by an interstitially placed laser diffuser. We hypothesized that ultrasound‐based image guidance yields improved tumor treatment outcomes in terms of tumor regression and survival by improving the accuracy of the placement of the laser fiber and nanoparticles within a tumor and facilitating more precise PTT delivery. To test this hypothesis, we assessed the effect of ultrasound‐guided I‐PTT (US I‐PTT) on neuroblastoma, an aggressive solid tumor of childhood, using the 9464D syngeneic model in C57BL/6 mice. US I‐PTT using Prussian blue nanoparticles activated by an interstitial cylindrical laser diffuser generated an equivalent in vivo thermal dose as blinded, non‐image‐guided I‐PTT (B I‐PTT). However, US I‐PTT resulted in significantly higher treatment accuracy compared to B I‐PTT, attributable to the image guidance. Importantly, this improved accuracy translated to improved treatment outcomes wherein mice treated with US I‐PTT exhibited significantly improved tumor regression, tumor‐free survival, and long‐term survival compared to mice treated with B I‐PTT. Further, histological analyses of the tumors post‐PTT confirmed the advantages conferred by US I‐PTT over B I‐PTT for tumor control. These proof‐of‐concept results demonstrate the value of using ultrasound guidance for I‐PTT treatment and the translational implications of this approach to provide a more accurate and effective treatment for neuroblastoma.
我们描述了在实施间质光热疗法（I-PTT）这种实验性癌症治疗模式时，如何利用超声图像引导来提高治疗效果。间质光热疗法是一种很有前景的肿瘤热疗方法，通过间质放置的激光扩散器激活肿瘤内注射的纳米颗粒光热剂。我们假设，基于超声波的图像引导可以提高激光光纤和纳米粒子在肿瘤内放置的准确性，促进更精确的 PTT 输送，从而在肿瘤消退和存活率方面改善肿瘤治疗效果。为了验证这一假设，我们使用 C57BL/6 小鼠 9464D 合成模型评估了超声引导下 I-PTT（US I-PTT）对神经母细胞瘤（一种侵袭性儿童实体瘤）的效果。使用由间隙圆柱形激光扩散器激活的普鲁士蓝纳米粒子的 US I-PTT，产生的体内热剂量与盲法非图像引导 I-PTT（B I-PTT）相当。然而，与 B 型 I-PTT 相比，US 型 I-PTT 的治疗准确性明显更高，这要归功于图像引导。重要的是，这种准确性的提高转化为治疗效果的改善，与使用 B I-PTT 治疗的小鼠相比，使用 US I-PTT 治疗的小鼠在肿瘤消退、无瘤生存和长期生存方面都有明显改善。此外，PTT 后的肿瘤组织学分析证实了 US I-PTT 比 B I-PTT 在控制肿瘤方面的优势。这些概念验证结果证明了使用超声引导进行 I-PTT 治疗的价值，以及这种方法的转化意义，即为神经母细胞瘤提供一种更准确、更有效的治疗方法。
{"title":"Ultrasound‐guided interstitial photothermal therapy generates improved treatment responses in a 9464D model of neuroblastoma","authors":"Grace E. Olsson, Rohan V. Patil, Samantha J. Chin, Katharine N. Rus, Elizabeth E. Sweeney, Karun V. Sharma, Rohan Fernandes","doi":"10.1002/btm2.10749","DOIUrl":"https://doi.org/10.1002/btm2.10749","url":null,"abstract":"We describe the use of ultrasound image guidance to improve treatment outcomes when administering interstitial photothermal therapy (I‐PTT), an experimental cancer treatment modality. I‐PTT is a promising thermal therapy for tumors using intratumorally injected nanoparticle‐based photothermal agents activated by an interstitially placed laser diffuser. We hypothesized that ultrasound‐based image guidance yields improved tumor treatment outcomes in terms of tumor regression and survival by improving the accuracy of the placement of the laser fiber and nanoparticles within a tumor and facilitating more precise PTT delivery. To test this hypothesis, we assessed the effect of ultrasound‐guided I‐PTT (US I‐PTT) on neuroblastoma, an aggressive solid tumor of childhood, using the 9464D syngeneic model in C57BL/6 mice. US I‐PTT using Prussian blue nanoparticles activated by an interstitial cylindrical laser diffuser generated an equivalent in vivo thermal dose as blinded, non‐image‐guided I‐PTT (B I‐PTT). However, US I‐PTT resulted in significantly higher treatment accuracy compared to B I‐PTT, attributable to the image guidance. Importantly, this improved accuracy translated to improved treatment outcomes wherein mice treated with US I‐PTT exhibited significantly improved tumor regression, tumor‐free survival, and long‐term survival compared to mice treated with B I‐PTT. Further, histological analyses of the tumors post‐PTT confirmed the advantages conferred by US I‐PTT over B I‐PTT for tumor control. These proof‐of‐concept results demonstrate the value of using ultrasound guidance for I‐PTT treatment and the translational implications of this approach to provide a more accurate and effective treatment for neuroblastoma.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"28 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934845","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}
Nazente Atceken, Ikra Bayaki, Berk Can, Defne Yigci, Savas Tasoglu
Human Mpox disease (MPX) is an endemic zoonotic disease that develops when patients are infected with the Mpox virus (MPXV). MPXV shares a high level of genetic similarity to other poxviruses and the clinical presentation of MPX is similar to other poxvirus infections which can result in a delay in diagnosis. In addition, the MPXV virus is phylogenetically divided into two different clades which affects the severity of disease. In recent years, there has been an unusual worldwide spread of MPXV, leading to a global public health problem. The most important step in the fight against MPX is rapid, highly specific, and accurate diagnosis. Following the rapid spread of disease in recent years, efforts to develop diagnostic tests have gained momentum. Here, MPX, MPX epidemiology, and MPX diagnostic tests are discussed. Furthermore, biochemical diagnostic tests, molecular diagnostic tests and their development, and point‐of‐care (PoC) diagnostic applications are reviewed. Molecular diagnostic technologies such as polymerase chain reaction, recombinase polymerase amplification, and loop‐mediated isothermal amplification methods that detect MPX are evaluated. Additionally, next‐generation combined molecular techniques and their importance in PoC transition are explored.
{"title":"Mpox disease, diagnosis, and point of care platforms","authors":"Nazente Atceken, Ikra Bayaki, Berk Can, Defne Yigci, Savas Tasoglu","doi":"10.1002/btm2.10733","DOIUrl":"https://doi.org/10.1002/btm2.10733","url":null,"abstract":"Human Mpox disease (MPX) is an endemic zoonotic disease that develops when patients are infected with the Mpox virus (MPXV). MPXV shares a high level of genetic similarity to other poxviruses and the clinical presentation of MPX is similar to other poxvirus infections which can result in a delay in diagnosis. In addition, the MPXV virus is phylogenetically divided into two different clades which affects the severity of disease. In recent years, there has been an unusual worldwide spread of MPXV, leading to a global public health problem. The most important step in the fight against MPX is rapid, highly specific, and accurate diagnosis. Following the rapid spread of disease in recent years, efforts to develop diagnostic tests have gained momentum. Here, MPX, MPX epidemiology, and MPX diagnostic tests are discussed. Furthermore, biochemical diagnostic tests, molecular diagnostic tests and their development, and point‐of‐care (PoC) diagnostic applications are reviewed. Molecular diagnostic technologies such as polymerase chain reaction, recombinase polymerase amplification, and loop‐mediated isothermal amplification methods that detect MPX are evaluated. Additionally, next‐generation combined molecular techniques and their importance in PoC transition are explored.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"1 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925001","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}
Ajay Tijore, Felix Margadant, Nehal Dwivedi, Leslie Morgan, Mingxi Yao, Anushya Hariharan, Claire Alexandra Zhen Chew, Simon Powell, Glenn Kunnath Bonney, Michael Sheetz
Recent studies show that tumor cells undergo apoptosis after mechanical stretching, which promotes normal cell growth. Since ultrasound can produce similar sub‐cellular mechanical stresses on the nanoscale, here we test the effect of ultrasound‐mediated mechanical forces on tumors and normal cell survival. Surprisingly, tumor cells undergo apoptosis through a calpain‐dependent mitochondrial pathway that relies upon calcium entry through the mechanosensitive Piezo1 channels. This is a general property of all tumor cell lines tested irrespective of tissue origin, but normal cells are unaffected. In vivo, ultrasound treatment promotes tumor cell killing in a mouse model with invasive CT26 cancer cell subcutaneous tumors and in the chick chorioallantoic membrane (CAM) model with relatively minor damage to chick embryos. Further, patient‐derived pancreatic tumor organoids are killed by ultrasound treatment. Because ultrasound‐mediated mechanical forces cause apoptosis of tumor cells from many different tissues in different microenvironments, it may offer a safe, non‐invasive approach to augment tumor treatments.
{"title":"Ultrasound‐mediated mechanical forces activate selective tumor cell apoptosis","authors":"Ajay Tijore, Felix Margadant, Nehal Dwivedi, Leslie Morgan, Mingxi Yao, Anushya Hariharan, Claire Alexandra Zhen Chew, Simon Powell, Glenn Kunnath Bonney, Michael Sheetz","doi":"10.1002/btm2.10737","DOIUrl":"https://doi.org/10.1002/btm2.10737","url":null,"abstract":"Recent studies show that tumor cells undergo apoptosis after mechanical stretching, which promotes normal cell growth. Since ultrasound can produce similar sub‐cellular mechanical stresses on the nanoscale, here we test the effect of ultrasound‐mediated mechanical forces on tumors and normal cell survival. Surprisingly, tumor cells undergo apoptosis through a calpain‐dependent mitochondrial pathway that relies upon calcium entry through the mechanosensitive Piezo1 channels. This is a general property of all tumor cell lines tested irrespective of tissue origin, but normal cells are unaffected. In vivo, ultrasound treatment promotes tumor cell killing in a mouse model with invasive CT26 cancer cell subcutaneous tumors and in the chick chorioallantoic membrane (CAM) model with relatively minor damage to chick embryos. Further, patient‐derived pancreatic tumor organoids are killed by ultrasound treatment. Because ultrasound‐mediated mechanical forces cause apoptosis of tumor cells from many different tissues in different microenvironments, it may offer a safe, non‐invasive approach to augment tumor treatments.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"33 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908219","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}
Yoo‐Jung Lee, Byounggook Cho, Daeyeol Kwon, Yunkyung Kim, Saemin An, Soi Kang, Jongpil Kim
The generation of human cortical organoids containing outer radial glia (oRG) cells is crucial for modeling neocortical development. Here we show that Catalpol, an iridoid glucoside derived from Rehmannia glutinosa, significantly enhances the generation of cerebral organoids with expanded oRG populations and increased neurogenic potential. Catalpol‐treated organoids exhibited thicker ventricular zone/subventricular zone (VZ/SVZ) and outer subventricular zone (oSVZ) regions, with increased numbers of SOX2 + HOPX+ and SOX2 + TNC+ oRG cells and elevated expression of oRG markers HOPX and FAM107A. We found that Catalpol promoted oRG generation through non‐vertical divisions of ventricular radial glia (vRG) cells, indicating enhanced oRG generation via asymmetrical divisions. Furthermore, we demonstrated that Catalpol augmented oRG cell numbers through activation of the STAT3 signaling pathway. These findings highlight Catalpol's potential in promoting the generation of cerebral organoids with expanded oRG populations and increased neurogenic potential through STAT3 activation, offering new insights into neocortical development modeling.
{"title":"Catalpol promotes the generation of cerebral organoids with oRGs through activation of STAT3 signaling","authors":"Yoo‐Jung Lee, Byounggook Cho, Daeyeol Kwon, Yunkyung Kim, Saemin An, Soi Kang, Jongpil Kim","doi":"10.1002/btm2.10746","DOIUrl":"https://doi.org/10.1002/btm2.10746","url":null,"abstract":"The generation of human cortical organoids containing outer radial glia (oRG) cells is crucial for modeling neocortical development. Here we show that Catalpol, an iridoid glucoside derived from <jats:italic>Rehmannia glutinosa</jats:italic>, significantly enhances the generation of cerebral organoids with expanded oRG populations and increased neurogenic potential. Catalpol‐treated organoids exhibited thicker ventricular zone/subventricular zone (VZ/SVZ) and outer subventricular zone (oSVZ) regions, with increased numbers of SOX2 + HOPX+ and SOX2 + TNC+ oRG cells and elevated expression of oRG markers HOPX and FAM107A. We found that Catalpol promoted oRG generation through non‐vertical divisions of ventricular radial glia (vRG) cells, indicating enhanced oRG generation via asymmetrical divisions. Furthermore, we demonstrated that Catalpol augmented oRG cell numbers through activation of the STAT3 signaling pathway. These findings highlight Catalpol's potential in promoting the generation of cerebral organoids with expanded oRG populations and increased neurogenic potential through STAT3 activation, offering new insights into neocortical development modeling.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"327 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902021","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}
Changrui Zhao, Kun Fu, Jiameng Tian, Tian Long, Jianzhong Song, Siyu Chen, Chang Liu
With papillary thyroid carcinoma (PTC) rates rising significantly, concerns about conventional treatments like thyroidectomy and radiotherapy highlight the need for non‐invasive options. Our study explores photobiomodulation therapy (PBMT), which uses specific light wavelengths to evoke cellular responses in PTC treatment. Our research utilized a custom‐designed optical system to investigate PBMT, finding that blue light at a wavelength of 465 nm can safely and effectively inhibit the proliferation of the TPC‐1 PTC cell line by inducing cell cycle arrest. Additionally, we developed a wirelessly powered wearable PBMT device, which is equipped with an advanced light delivery system that ensures precise and consistent dosage. This device designed for optimal patient comfort, effectively suppressed tumor growth in mouse models without adverse effects. PBMT indicates thyroid tissue's light responsiveness as a non‐visual organ. Our study's innovative approach integrates the disciplines of oncology, biophysics, and medical device technology, thereby advancing the treatment paradigms for PTC. This interdisciplinary bridge not only highlights our groundbreaking findings but also paves the way for future research in cancer therapy and photomedicine.
{"title":"Wearable photobiomodulation halts thyroid cancer growth by leveraging thyroid photosensitivity","authors":"Changrui Zhao, Kun Fu, Jiameng Tian, Tian Long, Jianzhong Song, Siyu Chen, Chang Liu","doi":"10.1002/btm2.10734","DOIUrl":"https://doi.org/10.1002/btm2.10734","url":null,"abstract":"With papillary thyroid carcinoma (PTC) rates rising significantly, concerns about conventional treatments like thyroidectomy and radiotherapy highlight the need for non‐invasive options. Our study explores photobiomodulation therapy (PBMT), which uses specific light wavelengths to evoke cellular responses in PTC treatment. Our research utilized a custom‐designed optical system to investigate PBMT, finding that blue light at a wavelength of 465 nm can safely and effectively inhibit the proliferation of the TPC‐1 PTC cell line by inducing cell cycle arrest. Additionally, we developed a wirelessly powered wearable PBMT device, which is equipped with an advanced light delivery system that ensures precise and consistent dosage. This device designed for optimal patient comfort, effectively suppressed tumor growth in mouse models without adverse effects. PBMT indicates thyroid tissue's light responsiveness as a non‐visual organ. Our study's innovative approach integrates the disciplines of oncology, biophysics, and medical device technology, thereby advancing the treatment paradigms for PTC. This interdisciplinary bridge not only highlights our groundbreaking findings but also paves the way for future research in cancer therapy and photomedicine.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"7 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867274","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}
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