Article
Multidisciplinary Sciences
Bob A. Hersbach, Tatiana Simon, Giacomo Masserdotti
Summary: Direct neuronal reprogramming is a powerful technique that can generate functional neurons from different starter cell populations without the need for multipotent intermediates. This has great potential in disease modeling and as an alternative for cell-based replacement therapies. The conversion of differentiated non-neural cells, such as astrocytes, into functional neurons in vitro has provided important insights into the molecular mechanisms and challenges of efficient reprogramming. However, comparing results from different labs is difficult due to variations in isolation, culture, and reprogramming methods. This article provides a detailed protocol for reliably isolating and culturing astrocytes with high purity, as well as protocols for reprogramming them into neurons.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2022)
Article
Biochemical Research Methods
Yanfang Chen, Severine Roselli, Nikita Panicker, Joshua S. Brzozowski, David A. Skerrett-Byrne, Heather C. Murray, Nicole M. Verrills
Summary: This article provides a comprehensive characterization of the proteome and phosphoproteome of wild-type primary MEFs from C57BL/6 mice. The study identifies abundant EIF2/4 and MTOR signaling pathways, as well as extracellular matrix and cytoskeleton associated pathways. Kinase enrichment analysis reveals the activation of P38A, P90RSK, P70S6K, and MTOR. This dataset serves as a valuable resource for future research in the field.
Article
Multidisciplinary Sciences
Gintautas Vainorius, Maria Novatchkova, Georg Michlits, Juliane Christina Baar, Cecilia Raupach, Joonsun Lee, Ramesh Yelagandula, Marius Wernig, Ulrich Elling
Summary: In this study, the authors show that cells can take two mechanistically distinct paths in the same transition paradigm when driven by the similar proneural factors Ascl1 and Ngn2. Ascl1 dismantles the pluripotency network and installs neuronal and trophoblast cell fates, while Ngn2 generates a neural stem cell-like intermediate supported by incomplete shutdown of the pluripotency network.
NATURE COMMUNICATIONS
(2023)
Article
Gastroenterology & Hepatology
Yunfei Bai, Zhenghao Yang, Xiaochan Xu, Wanqiu Ding, Juntian Qi, Feng Liu, Xiaoxiao Wang, Bin Zhou, Wenpeng Zhang, Xiaomei Zhuang, Guanglu Li, Yang Zhao
Summary: Cell fate can be directly reprogrammed into functional cell types using small molecule stimuli. This study demonstrates the successful direct chemical reprogramming of mouse fibroblasts into functional hepatocyte-like cells. The chemically induced hepatocytes exhibit comparable activity and function to primary hepatocytes and have high-quality physiological properties. The findings suggest the potential of chemical reprogramming in organ/tissue repair and regeneration therapies.
Article
Multidisciplinary Sciences
Adriaan Merlevede, Emilie M. Legault, Viktor Drugge, Roger A. Barker, Janelle Drouin-Ouellet, Victor Olariu
Summary: Direct reprogramming of adult skin fibroblasts into neurons is controlled by interacting gene regulators, and the dynamics of these interactions are crucial for cellular decision making. A quantitative model of the governing gene regulatory system, supported by mRNA expression measurements, was proposed to capture the accurate gene interaction dynamics and predict the outcome of various experiments. Experimental validation demonstrated the importance of nPTB feedback for successful neural conversion, and a novel analytical technique was introduced to dissect system behavior and reveal the influence of individual factors on gene expression. Overall, computational analysis proves to be a powerful tool for understanding the mechanisms of direct (neuronal) reprogramming and improving cell conversion strategies in the future.
SCIENTIFIC REPORTS
(2021)
Review
Cell Biology
Lakshmy Vasan, Eunjee Park, Luke Ajay David, Taylor Fleming, Carol Schuurmans
Summary: Direct neuronal reprogramming is an innovative technology that converts somatic cells into induced neurons without passing through a pluripotent state. The capacity to create new neurons in the brain has opened up possibilities for treating incurable neurodegenerative diseases and brain injuries. By identifying intrinsic and extrinsic cues, developmental biologists have paved the way for this field, leading to the development of new methodologies for neuronal reprogramming.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yihe Ma, Yumiao Lin, Wenting Huang, Xusheng Wang
Summary: The study explores the conversion of fibroblasts into dermal-papilla-cell-like cells using small molecules, with different fibroblasts requiring different compounds or combinations for conversion, and TTNPB alone efficiently converting adult mouse fibroblasts into DPC-LCs with stronger hair-inducing capacity. Transcriptome analysis reveals increased expression of genes associated with hair-inducing capacity in DPC-LCs, suggesting the potential of this pharmacological approach for hair follicle regeneration and hair loss therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Endocrinology & Metabolism
Constanza Contreras-Jurado, Ana Montero-Pedrazuela, Raul F. Perez, Susana Alemany, Mario F. Fraga, Ana Aranda
Summary: This study found that triiodothyronine (T3), a thyroid hormone, enhances the reprogramming of mouse embryonic fibroblasts (MEFs) into induced pluripotent stem cells (iPSCs). T3-induced iPSCs show similar characteristics to embryonic stem cells and have the potential for differentiation into the three major germ layers. The inclusion of T3 in reprogramming strategies could be useful for studying cell plasticity, disease, and regenerative medicine.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ryogo Katada, Junichi Tanaka, Koki Takamatsu, Kenji Hata, Rika Yasuhara, Shintaro Ohnuma, Ikuko Takakura, Riko Nishimura, Tatsuo Shirota, Kenji Mishima
Summary: Salivary gland hypofunction caused by radiation therapy or Sjogren syndrome can lead to various oral diseases and decrease in quality of life. Inducing salivary gland-like cells from transdifferentiated epithelial tissues provides a promising cell therapy strategy for treating dry mouth.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Cell Biology
Qiong Yang, Haosong Shi, Yizhou Quan, Qianqian Chen, Wang Li, Li Wang, Yonghui Wang, Zhongzhong Ji, Shan-Kai Yin, Hai-Bo Shi, Huiming Xu, Wei-Qiang Gao
Summary: The research provides a new method to induce mouse embryonic fibroblasts to differentiate into cells resembling inner ear hair cells in vitro, which is significant; these induced cells express multiple HC-specific proteins, exhibit structures and functions similar to inner ear hair cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Neurosciences
Riccardo Bocchi, Giacomo Masserdotti, Magdalena Goetz
Summary: A successful experiment conducted 20 years ago opened up the field of neuronal reprogramming, which has since made significant progress. These studies are not only important for clinical applications, but also provide fundamental insights into the mechanisms of cell conversion into neurons and the maintenance of neuronal identity.
Editorial Material
Biochemistry & Molecular Biology
Cristiana Mollinari, Daniela Merlo
Summary: Translating successful preclinical research in neurodegenerative diseases into clinical practice has been challenging. Human induced pluripotent stem cells are a powerful tool for studying the molecular mechanisms of disease onset and pathogenesis, but require time to differentiate and may lose age-related information.
NEUROCHEMICAL RESEARCH
(2021)
Article
Multidisciplinary Sciences
Jingyang Guan, Guan Wang, Jinlin Wang, Zhengyuan Zhang, Yao Fu, Lin Cheng, Gaofan Meng, Yulin Lyu, Jialiang Zhu, Yanqin Li, Yanglu Wang, Shijia Liuyang, Bei Liu, Zirun Yang, Huanjing He, Xinxing Zhong, Qijing Chen, Xu Zhang, Shicheng Sun, Weifeng Lai, Yan Shi, Lulu Liu, Lipeng Wang, Cheng Li, Shichun Lu, Hongkui Deng
Summary: This study demonstrates the chemical reprogramming of human somatic cells to human chemically induced pluripotent stem cells, which exhibit key features of embryonic stem cells. The induction of an intermediate plastic state and inhibition of the JNK pathway are crucial for successful chemical reprogramming.
Article
Cell Biology
Iyori Nojima, Ryusuke Hosoda, Yuki Toda, Yoshiki Saito, Naohiro Ueda, Kouhei Horimoto, Naotoshi Iwahara, Yoshiyuki Horio, Atsushi Kuno
Summary: Downregulation of IGFBP5 through activation of the ERK2 pathway is involved in replicative senescence in embryonic mouse fibroblasts.
Article
Cell Biology
Longfei Sun, Dandan Zhang, Liangshan Qin, Quanhui Liu, Guodong Wang, Deshun Shi, Ben Huang
Summary: In this study, bovine ear fibroblasts were chemically induced to differentiate into adipocyte-like cells using a small-molecule cocktail called RVB. These induced cells (CiADCs) exhibited similar morphology and gene expression patterns to natural adipocytes. Furthermore, RVB increased the expression of PPAR gamma and C/EBP alpha proteins. Signaling pathways including PPAR signaling pathway, PI3K-Akt signaling pathway, p53 signaling pathway, MAPK signaling pathway, and ECM-receptor interaction played a vital role in adipogenesis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Engineering, Biomedical
Bikramjit Basu, N. H. Gowtham, Yang Xiao, Surya R. Kalidindi, Kam W. Leong
Summary: This leading opinion review paper emphasizes the integration of data science concepts and algorithms with biomaterials science. It also highlights the need for a mathematically rigorous cross-disciplinary framework that allows for systematic quantitative exploration and curation of critical biomaterials knowledge, driven by the concept of "biomaterialomics" which integrates multi-omics data and high-dimensional analysis with artificial intelligence tools like machine learning. The formulation of this approach has been demonstrated for patient-specific implants, additive manufacturing, and bioelectronic medicine.
ACTA BIOMATERIALIA
(2022)
Article
Chemistry, Multidisciplinary
Chao Yang, Jianati Dawulieti, Kunbao Zhang, Chuanxu Cheng, Yawei Zhao, Hanze Hu, Mingqiang Li, Ming Zhang, Li Chen, Kam W. Leong, Dan Shao
Summary: Using a cationic, antibiotic-containing hydrogel wound dressing can effectively remove bacteria and proinflammatory factors, reducing complications and improving outcomes following abdominal injury.
ADVANCED FUNCTIONAL MATERIALS
(2022)
Article
Multidisciplinary Sciences
Tetsuhiro Harimoto, Jaeseung Hahn, Yu-Yu Chen, Jongwon Im, Joanna Zhang, Nicholas Hou, Fangda Li, Courtney Coker, Kelsey Gray, Nicole Harr, Sreyan Chowdhury, Kelly Pu, Clare Nimura, Nicholas Arpaia, Kam W. Leong, Tal Danino
Summary: This study developed a genetically encoded microbial encapsulation system with tunable and dynamic expression of surface capsular polysaccharides to enhance systemic delivery. The system allowed bacteria to temporarily evade immune attack and be effectively cleared in vivo. The results showed that this strategy increased the maximum tolerated dose of bacteria and improved anti-tumor efficacy.
Review
Nanoscience & Nanotechnology
Zhaoxu Tu, Yiling Zhong, Hanze Hu, Dan Shao, Rainer Haag, Michael Schirner, Jaewoo Lee, Bruce Sullenger, Kam W. Leong
Summary: Inflammation plays a crucial role in our body's response to injury or infection, but dysregulation can lead to chronic inflammation and inflammatory diseases. Biomaterials can enhance the efficacy of anti-inflammatory drugs by improving drug bioavailability and reducing side effects. Key elements of the inflammatory environment and the design of biomaterials for anti-inflammatory therapeutic strategies are discussed in this Review.
NATURE REVIEWS MATERIALS
(2022)
Article
Engineering, Biomedical
Yawen Ma, Huimin Lin, Peng Wang, Haocheng Yang, Jie Yu, Hao Tian, Tianyu Li, Shengfang Ge, Yilong Wang, Renbing Jia, Kam W. Leong, Jing Ruan
Summary: MicroRNA-based gene therapy using biocompatible nanocarriers shows promise in treating ocular melanoma by up-regulating tumor suppressor miR-30a-5p and inhibiting malignant phenotypes. The nanocarrier with high miRNA loading and redox-responsive release capabilities enhances the therapeutic effect. Furthermore, it promotes M1 macrophage polarization and activates Fenton reaction, synergistically enhancing anti-tumor immunity. The study demonstrates the potential of this nanocarrier for targeted gene therapy in melanoma and other cancers.
ACTA BIOMATERIALIA
(2023)
Article
Chemistry, Multidisciplinary
Jiaqi Xu, Junchao Xu, Tongfei Shi, Yinlong Zhang, Fangman Chen, Chao Yang, Xinjing Guo, Guangna Liu, Dan Shao, Kam W. Leong, Guangjun Nie
Summary: Microbiota-based therapeutics offer innovative strategies to treat inflammatory bowel diseases (IBDs), but the clinical outcome and bacterial approach need improvement. Inspired by the benefits of probiotics, bioartificial probiotics are designed to restore intestinal microenvironment and shift the gut microbiome to an anti-inflammatory state. The bioartificial probiotic consists of E. coli Nissle 1917-derived membrane (EM) as the surface and biodegradable diselenide-bridged mesoporous silica nanoparticles (SeM) as the core. This work suggests a safe and effective nanomedicine for IBDs therapy.
ADVANCED MATERIALS
(2023)
Article
Engineering, Biomedical
Baoding Huang, Qianfen Wan, Tianyu Li, Lexiang Yu, Wen Du, Carmen Calhoun, Kam W. Leong, Li Qiang
Summary: As a solution to the chronic inflammation and local adiposity caused by obesity, cationic polyamidoamine (PAMAM) treatment has shown promising results in improving metabolic functions and reducing body weight in diet-induced obese (DIO) mice. The treatment involves the use of PAMAM generation 3 (P-G3) scavenger and complexing P-G3 with human serum albumin (HSA) to achieve sustained release. Local injection of HSA-PG3 successfully restricts the distribution of the complex within the targeted adipose tissue and reduces focal adiposity.
Article
Chemistry, Multidisciplinary
Naoto Yoshinaga, Joyce K. Zhou, Cong Xu, Chai Hoon Quek, Yuefei Zhu, Ding Tang, Lin Yung Hung, Sarah A. Najjar, Chin Ying Angela Shiu, Kara Gross Margolis, Yeh-Hsing Lao, Kam W. Leong
Summary: Effective delivery of CRISPR-Cas9 components is crucial and oral delivery has not been explored due to the degradative nature of the gastrointestinal tract. In this study, we developed novel PBA-functionalized CS-PEI polymers for oral CRISPR delivery, which showed effective penetration in the intestinal mucosa and achieved downregulation of the target protein and reduction in cholesterol. This study demonstrates the potential of addressing the needs of gene editing in a patient-compliant manner.
Article
Chemistry, Multidisciplinary
Jing Ruan, Fang Li, Hao Tian, Jie Yu, Hongpei Deng, Shengfang Ge, Kam W. Leong
Summary: This study presents a carbon dot-based photosensitizer that generates cytotoxic singlet oxygen (O-1(2)) through multiple pathways, improving the therapeutic efficacy of photodynamic therapy (PDT) for uveal melanoma.
Article
Nanoscience & Nanotechnology
Qianfen Wan, Baoding Huang, Tianyu Li, Yang Xiao, Ying He, Wen Du, Branden Z. Wang, Gregory F. Dakin, Michael Rosenbaum, Marcus D. Goncalves, Shuibing Chen, Kam W. Leong, Li Qiang
Summary: This research develops a nanomedicine based on polycation, which targets visceral fat selectively, preventing obesity and alleviating metabolic dysfunctions. By modulating nutrient-sensing signalling pathways, the polycation uncouples lipid synthesis and storage from adipocyte development, resulting in adipocytes with normal functions but deficient in hypertrophic growth. The study suggests the potential of cationic nanomaterials in treating metabolic diseases.
NATURE NANOTECHNOLOGY
(2022)
Article
Engineering, Biomedical
Ganchimeg Davaa, Jin Young Hong, Jung-Hwan Lee, Min Soo Kim, Jennifer O. Buitrago, Yu-Meng Li, Hae-Hyoung Lee, Dong Wook Han, Kam W. Leong, Jung Keun Hyun, Hae-Won Kim
Summary: Neural stem cells (NSC) have the potential to regenerate injured neural tissues, but suffer from low survival and uncontrolled differentiation. This study demonstrates that mechanically-tuned protein hydrogels can protect and enhance the long-term survival of reprogrammed NSC, alleviate neural inflammation, promote differentiation, and improve locomotor functions in treating injured spinal cord.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Cell Biology
Yunfei Li, Zhixiong Sun, Huixiang Zhu, Yan Sun, David B. Shteyman, Sander Markx, Kam W. Leong, Bin Xu, Bingmei M. Fu
Summary: The integrity of the blood-brain barrier formed by brain microvascular endothelial cells derived from 22q11.2 Deletion Syndrome patients is compromised. The haploinsufficiency of CRKL, a gene within the 22q11.2 DS deletion region, contributes to this deficit. Treatment with imatinib, an FDA-approved drug, restores the compromised blood-brain barrier by increasing the level of active forms of the CRKL protein.
Article
Engineering, Biomedical
Hye Sung Kim, Tzu-Chieh Ho, Moshe J. Willner, Michael W. Becker, Hae-Won Kim, Kam W. Leong
Summary: In this study, we propose an ex vivo T cell expansion system that mimics natural antigen-presenting cells for adoptive cell therapy. The system utilizes microfiber scaffolds coated with dendritic cell membrane to replicate the physicochemical properties of dendritic cells, leading to greater expansion and functionality of T cells. This scalable and customizable platform holds promise for future research and application in cell therapy.
BIOACTIVE MATERIALS
(2023)
Article
Chemistry, Multidisciplinary
Kaja I. Ritzau-Reid, Sebastien J. P. Callens, Ruoxiao Xie, Martina Cihova, Daniel Reumann, Christopher L. Grigsby, Lino Prados-Martin, Richard Wang, Axel C. Moore, James P. K. Armstrong, Juergen A. Knoblich, Molly M. Stevens
Summary: 3D organoids are widely used in vitro models for studying human development and disease. However, the current culture methods have limitations in terms of reproducibility and geometric control. A new approach combining stem cell biology and bioengineering is presented, using melt electrospinning writing to generate grid scaffolds that guide the self-organization of pluripotent stem cells. This method allows for high-throughput generation, culture, and analysis of organoids, reducing the time and labor involved in traditional methods.
ADVANCED MATERIALS
(2023)
Article
Chemistry, Multidisciplinary
Yongqiang Xiao, He Fang, Yuefei Zhu, Jie Zhou, Zhanzhan Dai, Hongxia Wang, Zhaofan Xia, Zhaoxu Tu, Kam W. Leong
Summary: This study investigates the effectiveness of cationic hyperbranched polyaminoglycosides derived from tobramycin (HPT) and disulfide-included HPT (ss-HPT) in scavenging cell-free nucleic acids (cfNAs) to mitigate posttrauma inflammation and hypercoagulation. Both polymers demonstrate the ability to suppress inflammation and hypercoagulation by efficiently scavenging cfNAs, and exhibit potent antibacterial effects. Additionally, these polymers exhibit favorable modulatory effects on inflammation and therapeutic outcomes in a mouse model. Notably, ss-HPT shows high accumulation and retention in injured organs of traumatized mice, with a higher biodegradation rate in healthy mice compared to HPT.