Article
Cell & Tissue Engineering
Xiao Fang, Xiong Fang, Yujia Mao, Aaron Ciechanover, Yan Xu, Jing An, Ziwei Huang
Summary: HF51116, a novel small molecule CXCR4 antagonist, can rapidly and potently mobilize HSCs from BM to PB in mice and monkeys. It synergizes with G-CSF to enhance mobilization efficacy and engraftment of HSCs, leading to successful long-term repopulation and survival in mice. HF51116 shows promising HSC mobilization activity in monkeys and warrants further preclinical and clinical studies.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Multidisciplinary Sciences
Runfeng Miao, Harim Chun, Xing Feng, Ana Cordeiro Gomes, Jungmin Choi, Joao P. Pereira
Summary: This study reveals that a complex homeostatic balance between hematopoietic stem cells (HSCs) and hematopoietic progenitor cells is maintained through competition for a limited amount of cell signaling molecule. When early hematopoietic progenitors fail to interact with specific cells, HSC numbers increase.
NATURE COMMUNICATIONS
(2022)
Review
Immunology
Ida Pastore, Emma Assi, Moufida Ben Nasr, Andrea Mario Bolla, Anna Maestroni, Vera Usuelli, Cristian Loretelli, Andy Joe Seelam, Ahmed Abdelsalam, Gian Vincenzo Zuccotti, Francesca D'Addio, Paolo Fiorina
Summary: Although progress has been made in understanding the pathophysiological mechanisms of T1D, the quest for effective therapeutic options is ongoing. Promising results have been seen with HSC-based approaches and teplizumab, but more research is needed to establish their long-term efficacy and safety. Genetically engineered HSCs hold potential as a novel biologic therapy for T1D and other autoimmune/immune-related disorders, with studies in murine models and humanized mouse models showing accelerated translational potentials.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Richard H. Smith, Hanan Bloomer, Danielle Fink, Keyvan Keyvanfar, Md Nasimuzzaman, Fatima Sancheznieto, Roop Dutta, Kacey Guenther Bui, Luigi J. Alvarado, Thomas R. Bauer, Dennis D. Hickstein, David W. Russell, Punam Malik, Johannes C. M. van der Loo, Steven L. Highfill, Douglas B. Kuhns, Mehdi Pirooznia, Andre Larochelle
Summary: This study provides pre-clinical evidence of the therapeutic usefulness of a foamy virus vector (FVV) for correcting genetic defects in LAD-1. Results showed that transduced cells displayed improvements in cellular chemotactic defects associated with LAD-1, and transplantation of vector-transduced cells in mice resulted in long-term engraftment. Vector insertion site analysis revealed no genotoxicity. These findings support the development of FVVs for ex vivo gene therapy of LAD-1.
HUMAN GENE THERAPY
(2022)
Article
Biochemistry & Molecular Biology
You Jung Hwang, Dong-Yeop Shin, Min-Jung Kim, Hyosun Jang, Soyeon Kim, Hyunwon Yang, Won Il Jang, Sunhoo Park, Sehwan Shim, Seung Bum Lee
Summary: This study found that SR1 could alleviate radiation-induced hematopoietic injury. It increased the survival rate and promoted the recovery of peripheral blood cell counts in irradiated mice. In vitro experiments also showed that SR1 increased the population of human hematopoietic stem/progenitor cells, reduced radiation-induced DNA damage and apoptosis. These results suggest that SR1 may be a potential radiomitigator for hematopoietic injury.
Article
Multidisciplinary Sciences
Devki D. Sukhtankar, Juan Jose Fung, Mi-na Kim, Thomas Cayton, Valerie Chiou, Nina G. Caculitan, Piotr Zalicki, Sujeong Kim, Yoonjung Jo, SoHui Kim, Jae Min Lee, Junhee Choi, SeongGyeong Mun, Ashley Chin, Yongdae Jang, Ji Yeong Lee, Gowoon Kim, Eun Hee Kim, Won-Ki Huh, Jae-Yeon Jeong, Dong-Seung Seen, Pina M. Cardarelli
Summary: Autologous Stem Cell Transplant (ASCT) is a common method for treating hematological malignancies. The combination of G-CSF and GPC-100 shows potential for sufficient and rapid collection of stem cells.
Review
Oncology
Juan Carlos Lopez-Gil, Laura Martin-Hijano, Patrick C. Hermann, Bruno Sainz Jr
Summary: This review summarizes the role of CXCL12 and its receptors in cancer stem cells and their niche, discusses therapeutic options, and highlights the need for a comprehensive review on the topic.
Article
Biochemistry & Molecular Biology
Nathalie Gerassimov, Colt Crain, Colin Bilyeu, Andrew Jacob, Chen-Ming Fan
Summary: Interactions between muscle stem cells (MuSCs) and extracellular matrix (ECM) proteins are crucial for muscle regeneration. Beta 3-integrin plays a critical role in the myogenic differentiation of C2C12 cells, but its role in MuSCs is still unclear.
Review
Immunology
Carsten Riether
Summary: Adult bone marrow hematopoietic stem cells (HSCs) maintain their function through interactions with regulatory T cells (Tregs). In leukemia, these regulatory mechanisms are disrupted, leading to compromised treatment outcomes.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Tiago C. Luis, Nikolaos Barkas, Joana Carrelha, Alice Giustacchini, Stefania Mazzi, Ruggiero Norfo, Bishan Wu, Affaf Aliouat, Jose A. Guerrero, Alba Rodriguez-Meira, Tiphaine Bouriez-Jones, Iain C. Macaulay, Maria Jasztal, Guangheng Zhu, Heyu Ni, Matthew J. Robson, Randy D. Blakely, Adam J. Mead, Claus Nerlov, Cedric Ghevaert, Sten Eirik W. Jacobsen
Summary: In this study, the researchers uncover a feedback mechanism in which IL-1 secreted by activated platelets signals through niche Lepr+ cells to activate HSCs and restore platelet homeostasis.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Xing Feng, Ruifeng Sun, Moonyoung Lee, Xinyue Chen, Shangqin Guo, Huimin Geng, Marcus Muschen, Jungmin Choi, Joao Pedro Pereira
Summary: Acute lymphoblastic and myeloblastic leukemias (ALL and AML) modify the bone marrow microenvironment and disrupt non-malignant hematopoiesis. Leukemic cells express lymphotoxin alpha 1 beta 2 and activate lymphotoxin beta receptor (LT beta R) signaling in mesenchymal stem cells (MSCs), which turns off IL7 production and prevents non-malignant lymphopoiesis. Genetic or pharmacological disruption of LT beta R signaling in MSCs restores lymphopoiesis but not erythropoiesis, reduces leukemic cell growth, and extends the survival of transplant recipients.
Article
Cell & Tissue Engineering
Keane Jared Guillaume Kenswil, Paola Pisterzi, Gonzalo Sanchez-Duffhues, Claire van Dijk, Andrea Lolli, Callie Knuth, Byambasuren Vanchin, Adrian Christopher Jaramillo, Remco Michiel Hoogenboezem, Mathijs Arnoud Sanders, Jacqueline Feyen, Tom Cupedo, Ivan G. Costa, Ronghui Li, Eric Monique Johannes Bindels, Kirsten Lodder, Bianca Blom, Pieter Koen Bos, Marie-Jose Goumans, Peter ten Dijke, Eric Farrell, Guido Krenning, Marc Hermanus Gerardus Petrus Raaijmakers
Summary: Rare LNGFR(+) cells in human fetal and regenerative bone marrow co-express endothelial and stromal markers, display features of endothelial-to-mesenchymal transition, and can generate tissue-forming BMSCs. EndoMT shows robust and sustained contributions to bone precursor and hematopoietic niche pools, with IL-33 overexpression driving the conversion process.
Review
Cell Biology
Rohan Kulkarni
Summary: Aging is associated with increased risk of various hematological disorders and myeloproliferative disorders. Hematopoietic stem cells (HSCs) play a crucial role in regulating the production of blood cells throughout life. Early growth response factor 1 (EGR1) is a key transcription factor controlling HSC proliferation and localization in the bone marrow. Downregulation of EGR1 activates HSCs for proliferation and differentiation, while increased expression of EGR1 is implicated in immune aging of HSCs and associated with hematological malignancies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Diana Sa da Bandeira, Alastair Morris Kilpatrick, Madalena Marques, Mario Gomez-Salazar, Telma Ventura, Zaniah Nashira Gonzalez, Dorota Stefancova, Fiona Rossi, Matthieu Vermeren, Chris Sebastiaan Vink, Mariana Beltran, Neil Cowan Henderson, Bongnam Jung, Reinier van der Linden, Harmen Jan George van de Werken, Wilfred F. J. van Ijcken, Christer Betsholtz, Stuart John Forbes, Henar Cuervo, Mihaela Crisan
Summary: This study reveals the expression of PDGFRβ in distinct perivascular stromal cell layers in mice and shows that its deletion impairs hematopoiesis. The study also demonstrates that PDGFRβ(+) cells play a dual role in murine hematopoiesis, acting as support for HSPCs in the aortic niche and giving rise to a subset of HSPCs that persist into adulthood.
Review
Biology
Shiru Yuan, Guohuan Sun, Yawen Zhang, Fang Dong, Hui Cheng, Tao Cheng
Summary: The study describes the SMART model developed based on data from HSC studies, aiming to delineate the key characteristics of adult stem cells and speculate on the physiological relevance of stem cells in other tissues. Efforts are now being made to understand ASC biology and develop safe and effective ASC-based therapies.
SCIENCE CHINA-LIFE SCIENCES
(2021)
Article
Clinical Neurology
Tobias Bobinger, Sebastian S. Roeder, Maximilian I. Spruegel, Kilian Froehlich, Vanessa D. Beuscher, Philip Hoelter, Hannes Lucking, Denis Corbeil, Hagen B. Huttner
Summary: The amount of membrane particle-associated CD133 in the CSF of patients with SAH and ICH is significantly increased compared to healthy patients, and declines during the hospital stay. Persistent elevation of CD133-positive membrane particles within the first week may represent a possible surrogate measure for impaired functional outcome in patients with SAH.
JOURNAL OF NEUROSURGERY
(2021)
Article
Multidisciplinary Sciences
Diane Dayoung Park, Chatchai Phoomak, Gege Xu, Laura P. Olney, Khiem A. Tran, Simon S. Park, Nathan E. Haigh, Guillaume Luxardi, Worachart Lert-itthiporn, Michiko Shimoda, Qiongyu Li, Nobuyuki Matoba, Fernando Fierro, Sopit Wongkham, Emanual Maverakis, Carlito B. Lebrilla
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Review
Medicine, Research & Experimental
Aurelio Lorico, Marco Lorico-Rappa, Jana Karbanova, Denis Corbeil, Giuseppe Pizzorno
Summary: In this review, the history of CD9 involvement in oncogenesis and cancer metastasis is briefly discussed, highlighting its potential value as a tumor-associated antigenic target. CD9 has been identified as a favorable prognostic marker or predictor of metastatic potential depending on the cancer type. Besides its use as an antigenic biomarker, CD9 plays a role in intercellular communication under physiological and pathological conditions, notably in the establishment of cancer metastases.
EXPERIMENTAL BIOLOGY AND MEDICINE
(2021)
Article
Agronomy
Amanda Kaye Hodson, Andrew Cicchetto, Fernando Antonio Fierro
Summary: Species-specific primers were designed and real-time PCR assays were developed for lesion and ring nematodes, showing strong correlation with microscopic counts. This high-throughput molecular quantification method could reduce diagnostic costs and provide more accurate information on nematode populations in the field.
Article
Biochemistry & Molecular Biology
Kayla Templeton, Meiby Ramos, Jacqueline Rose, Bryan Le, Qingwen Zhou, Amin Cressman, Stephanie Ferreyra, Carlito B. Lebrilla, Fernando Antonio Fierro
Summary: The study demonstrates that sialylation of N-glycans in MSCs is tightly regulated in response to environmental cues, with the inhibition of sialylation by 3F-Neu5Ac resulting in increased adhesion, migration, and survival of MSCs, while also inhibiting osteogenic and adipogenic differentiation. Additionally, the secretion of key trophic factors by MSCs is variably affected upon exposure to 3F-Neu5Ac, suggesting glycoengineering MSCs to reduce sialylated N-glycans could enhance their therapeutic potential.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Jianping Li, Julia Hlavka-Zhang, Jonathan H. Shrimp, Crissandra Piper, Daphne Dupere-Richer, Jacob S. Roth, Duohui Jing, L. Heidi, Casellas Roman, Catalina Troche, Alok Swaroop, Marta Kulis, Jon A. Oyer, Christine M. Will, Min Shen, Alberto Riva, Richard L. Bennett, Adolfo A. Ferrando, Matthew D. Hall, Richard B. Lock, Jonathan D. Licht
Summary: Mutations in the NSD2 histone methyltransferase (p.E1099K) were found to drive the relapse of pediatric acute lymphoblastic leukemia (ALL). These NSD2-mutant cells exhibited resistance to glucocorticoids, which was restored by correcting the mutation. The resistance was due to decreased expression of glucocorticoid receptor (GR) and the failure of glucocorticoids to activate GR expression. The use of PRC2 inhibitors reversed the glucocorticoid resistance by restoring GR levels and activation of proapoptotic genes, providing a potential therapeutic approach for relapsed ALL associated with NSD2 mutation.
Editorial Material
Oncology
Christine A. Fargeas, Aurelio Lorico, Denis Corbeil
FRONTIERS IN ONCOLOGY
(2021)
Article
Cell Biology
Mark F. Santos, Germana Rappa, Jana Karbanova, Simona Fontana, Maria Antonietta Di Bella, Marshall R. Pope, Barbara Parrino, Stella Maria Cascioferro, Giulio Vistoli, Patrizia Diana, Girolamo Cirrincione, Goffredo O. Arena, Gyunghwi Woo, Kevin Huang, Tony Huynh, Marta Moschetti, Riccardo Alessandro, Denis Corbeil, Aurelio Lorico
Summary: The antifungal compound itraconazole disrupts the binding of Rab7 to ORP3-VAP-A complexes, inhibiting EV-mediated pro-metastatic morphological changes such as cell migration in colon cancer cells. This discovery may lead to the development of new therapeutic approaches for cancer treatment.
JOURNAL OF EXTRACELLULAR VESICLES
(2021)
Article
Engineering, Biomedical
Hsin-ya Yang, Fernando Fierro, Daniel J. Yoon, Anthony Gallegos, Stephanie L. Osborn, Alan Nguyen, Thomas R. Peavy, William Ferrier, Linda Talken, Betty W. Ma, Kristopher G. Galang, Andrea Medina Lopez, Daniel R. Fregoso, Heather Stewart, Eric A. Kurzrock, Athena M. Soulika, Jan A. Nolta, R. Rivkah Isseroff
Summary: A combination treatment involving human mesenchymal stem/stromal cells (MSCs) embedded in an extracellular matrix scaffold and preconditioned with hypoxia and the beta-adrenergic receptor antagonist timolol, combined with sustained application of timolol post implantation, has shown promising results for improving wound healing in a diabetic mouse model. This study extends those findings to a porcine wound model, further demonstrating the efficacy and safety of the combined treatment in promoting wound reepithelialization and angiogenesis while maintaining a safe concentration of timolol in the plasma.
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
(2022)
Article
Neurosciences
Peter Deng, Julian A. N. M. Halmai, Ulrika Beitnere, David Cameron, Michele L. Martinez, Charles C. Lee, Jennifer J. Waldo, Krista Thongphanh, Anna Adhikari, Nycole Copping, Stela P. Petkova, Ruth D. Lee, Samantha Lock, Miranda Palomares, Henriette O'Geen, Jasmine Carter, Casiana E. Gonzalez, Fiona K. B. Buchanan, Johnathan D. Anderson, Fernando A. Fierro, Jan A. Nolta, Alice F. Tarantal, Jill L. Silverman, David J. Segal, Kyle D. Fink
Summary: This study demonstrates the use of a mesenchymal stem/stromal cell (MSC)-based delivery system for the secretion of a ZF protein, which has shown promising results in transgenic mouse models and young rhesus monkeys. It provides a less invasive approach for effective in vivo delivery of ZF protein to treat genetic disorders.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Oncology
Lila Bemmerlein, Ilker A. Deniz, Jana Karbanova, Angela Jacobi, Stephan Drukewitz, Theresa Link, Andy Goebel, Lisa Sevenich, Anna V. Taubenberger, Pauline Wimberger, Jan Dominik Kuhlmann, Denis Corbeil
Summary: This study investigates the use of cell morphology to predict bone metastasis in breast cancer. The researchers found that the morphology of breast cancer cells can reflect their molecular, migratory, and biophysical characteristics, and is specifically altered in cells that adopt a bone-tropic phenotype. The findings suggest that cell morphology could be an informative readout for understanding breast cancer heterogeneity and predicting bone metastasis.
Article
Cell Biology
Mark F. Santos, Germana Rappa, Simona Fontana, Jana Karbanova, Feryal Aalam, Derek Tai, Zhiyin Li, Marzia Pucci, Riccardo Alessandro, Chikao Morimoto, Denis Corbeil, Aurelio Lorico
Summary: Intercellular communication between cancer cells and healthy cells in the tumor microenvironment plays a crucial role in cancer progression and metastasis. Extracellular vesicles (EVs) have emerged as novel mediators in this communication. In this study, the researchers developed a monovalent Fab fragment antibody targeting CD9 tetraspanin and demonstrated its effectiveness in blocking the internalization of melanoma cell-derived EVs and the transfer of their cargo proteins. The study also showed the potential of this anti-CD9 Fab antibody in inhibiting the phenotypic transformation and migration of colorectal cancer cells. Intercepting EV-mediated communication in the tumor niche with this antibody could lead to new anti-cancer therapeutic strategies.
Article
Cell Biology
Ilker A. Deniz, Jana Karbanova, Manja Wobus, Martin Bornhaeuser, Pauline Wimberger, Jan Dominik Kuhlmann, Denis Corbeil
Summary: In this study, it is found that MSCs isolated from bone marrow can generate migrasomes, a newly discovered organelle involved in intercellular communication. Migrasomes have the ability to attract both leukemic cells and hematopoietic progenitors, possibly through the SDF-1 signaling pathway.
CELL COMMUNICATION AND SIGNALING
(2023)
Review
Cell Biology
Goffredo O. Arena, Stefano Forte, Mohamed Abdouh, Cheryl Vanier, Denis Corbeil, Aurelio Lorico
Summary: Metastasis, the spread of cancer cells to distant organs, is the main cause of cancer deaths. However, treatments have typically focused on inhibiting tumor growth rather than targeting the metastatic process. Recent research has explored alternative theories, such as the role of extracellular vesicles (EVs), in the spread of cancer cells. Understanding these processes is crucial for developing new therapies and improving cancer survival rates.
Article
Multidisciplinary Sciences
Mark F. Santos, Germana Rappa, Jana Karbanova, Patrizia Diana, Girolamo Cirrincione, Daniela Carbone, David Manna, Feryal Aalam, David Wang, Cheryl Vanier, Denis Corbeil, Aurelio Lorico
Summary: Santos et al. discovered that HIV-1 promotes nuclear envelope invagination through endocytosis mediated by VAP-A, ORP3, and Rab7 protein complex, allowing the virus to enter T-cell nuclei. This cellular pathway and its molecular players could be potential therapeutic targets and may be shared by other viruses requiring nuclear entry to complete their life cycle.
NATURE COMMUNICATIONS
(2023)