Review
Immunology
Thomas Menter, Alexandar Tzankov
Summary: This review examines the complex relationship between leukemic cells and the tumor microenvironment in AML, focusing on niche cells and T-cell subsets, and explores potential therapeutic strategies for manipulating the tumor microenvironment.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Takanori Yamaguchi, Eiji Kawamoto, Arong Gaowa, Eun Jeong Park, Motomu Shimaoka
Summary: Leukemia originates from hematopoietic stem cells in the bone marrow and treatment includes chemotherapy and hematopoietic stem cell transplantation. However, drug resistance and relapse remain challenges in leukemia management.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Immunology
Alice Pievani, Roberto Savoldelli, Juliane Poelchen, Elisa Mattioli, Giorgio Anselmi, Alice Girardot, Jochen Utikal, Pierre Bourdely, Marta Serafini, Pierre Guermonprez
Summary: Tissue engineering provides numerous opportunities in regenerative medicine, drug testing, and modeling hematopoiesis. Replicating the physiological microenvironments supporting leukocyte development is crucial for accurately modeling immune cell development. Immune niches are characterized by mesenchymal stromal cells that play unique roles in organizing niche development, maintenance, and function.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Oleg Kandarakov, Alexander Belyaysky, Ekaterina Semenova
Summary: This review discusses various aspects of organization and functioning of the HSC cell niche in bone marrow. The studies include the anatomy of BM niches, various cell types composing the niche, niches for more differentiated cells, metabolism of HSCs in relation to the niche, niche aging, and leukemic transformation of the niche.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Genetics & Heredity
Zuohua Chi, Liji Chen, Xiaomin Ye, Aimei Liu, Gongwang Yu, Yan Sun
Summary: Endothelial cells and perivascular cells together form a diverse network of blood vessels in the bone marrow, facilitating the delivery of blood cells, oxygen, and nutrients. These vessels create niches for hematopoietic stem and progenitor cells, providing signals for cell homing, self-renewal, and differentiation. Understanding the structure and function of the bone marrow vasculature niche is essential for developing advanced strategies in hematopoiesis reconstitution.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2022)
Article
Immunology
Lakshmi Sandhow, Huan Cai, Elory Leonard, Pingnan Xiao, Luana Tomaipitinca, Alma Mansson, Makoto Kondo, Xiaoyan Sun, Anne-Sofie Johansson, Karl Tryggvason, Maria Kasper, Marcus Jaras, Hong Qian
Summary: This study demonstrates the regenerative capacity of AML cells infiltrated in the skin and the role of skin mesenchymal niches in maintaining and protecting AML cells. It provides new insight into the pathology of leukemia cutis and suggests potential implications for AML relapse.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Review
Cell Biology
Anne Brunet, Margaret A. Goodell, Thomas A. Rando
Summary: Stem cell function declines during ageing, resulting in the loss of tissue integrity and health deterioration. This Review discusses the mechanisms underlying ageing in stem cells and their niches, and potential rejuvenation strategies.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2023)
Article
Oncology
Ran Li, Kai Xue, Junmin Li
Summary: FGF13 is lowly expressed in AML patients and its elevated expression is associated with prolonged survival. It is closely related to the bone marrow microenvironment, T cell count, immune checkpoint genes, and cytokines. Overexpression of FGF13 inhibits AML cell growth and prolongs the survival of recipient mice.
FRONTIERS OF MEDICINE
(2022)
Review
Cell Biology
Julia Froebel, Theresa Landspersky, Guelce Percin, Christina Schreck, Susann Rahmig, Alessandro Ori, Daniel Nowak, Marieke Essers, Claudia Waskow, Robert A. J. Oostendorp
Summary: The bone marrow environment, known as the niche, plays a vital role in maintaining blood cell formation throughout life. Different types of stress can disrupt the niche, leading to deregulation of hematopoietic stem cells and their function. Both acute and chronic insults can alter the cellular composition and structure of the niche, ultimately affecting hematopoiesis and increasing susceptibility to diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Engineering, Biomedical
Drew E. Glaser, Matthew B. Curtis, Peter A. Sariano, Zachary A. Rollins, Bhupinder S. Shergill, Aravind Anand, Alyssa M. Deely, Venktesh S. Shirure, Leif Anderson, Jeremy M. Lowen, Natalie R. Ng, Katherine Weilbaecher, Daniel C. Link, Steven C. George
Summary: A 3D in vitro model of human bone marrow containing perivascular and endosteal niches has been developed using microfluidic and stem cell technologies. This model can replicate in vivo bone marrow function and study dynamic events at the niche level, providing opportunities to advance our understanding of human bone marrow function and drug response.
Article
Multidisciplinary Sciences
Toshihiko Oki, Francois Mercier, Hiroki Kato, Yookyung Jung, Thomas O. McDonald, Joel A. Spencer, Michael C. Mazzola, Nick van Gastel, Charles P. Lin, Franziska Michor, Toshio Kitamura, David T. Scadden
Summary: This study investigates the real-time dynamics of the mTORC1 pathway in relation to AML growth and response to chemotherapy using fluorescent markers, showing a decrease and subsequent increase in mTORC1 activity with AML progression and maximal chemotherapy response, respectively. Data also suggests that chemotherapy induces mTORC1 activity, and timed inhibition of mTORC1 enhances killing of AML cells. These findings provide insights for targeted intervention strategies in AML treatment.
NATURE COMMUNICATIONS
(2021)
Article
Engineering, Biomedical
Michaela Petaroudi, Aleixandre Rodrigo-Navarro, Oana Dobre, Matthew J. Dalby, Manuel Salmeron-Sanchez
Summary: Living biointerfaces are a new type of biomaterials that combine living cells and polymeric matrices to act as instructive materials for surrounding cells. In this study, living biomaterials based on Lactococcus lactis expressing specific genes were used to control hematopoietic stem cells in both 2D and 3D environments. The results showed that these living biomaterials can direct the interaction between stem cells and bacteria, and can significantly expand the population of specific stem cells in 3D hydrogels. The findings suggest the potential of using genetically engineered bacteria-based living materials for ex-vivo expansion of stem cells and clinical applications in hematological disorders.
ADVANCED HEALTHCARE MATERIALS
(2022)
Article
Immunology
Juan Carlos Balandran, Jose Davila-Velderrain, Antonio Sandoval-Cabrera, Gabriela Zamora-Herrera, Vanessa Teran-Cerqueda, Lilia Adela Garcia-Stivalet, Jose Alejandro Limon-Flores, Erick Armenta-Castro, Aurora Rodriguez-Martinez, Bertha Alicia Leon-Chavez, Veronica Vallejo-Ruiz, Duane C. Hassane, Sonia Mayra Perez-Tapia, Vianney Ortiz-Navarrete, Monica L. Guzman, Rosana Pelayo
Summary: B-ALL originates from malignant lymphoid precursors in the bone marrow that hijack the microenvironment niches. Patient-derived leukemia spheroids (PDLS) enriched with leukemia cells displaying stem cell features are supported by CXCL11(+) MSCs within hypoxic microenvironments, mimicking key features of tumor reemergence and initiation. This system provides a unique opportunity for personalized ex vivo avatars for B-ALL patients to evaluate their own LIC pathobiology and drug sensitivity in the context of the tumor microenvironment.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biology
Zengdi Zhang, Zan Huang, Mohamed Awad, Mohammed Elsalanty, James Cray, Lauren E. Ball, Jason C. Maynard, Alma L. Burlingame, Hu Zeng, Kim C. Mansky, Hai-Bin Ruan
Summary: In mammals, the interaction between bone marrow stroma and hematopoietic progenitors contributes to bone-BM homeostasis, but the mechanisms and interactions between the development of skeletal and hematopoietic systems are largely unknown. This study reveals that the intracellular O-GlcNAc modification plays a role in dictating the fate and function of early BM stromal cells (BMSCs). O-GlcNAcylation promotes osteogenic differentiation of BMSCs and supports lymphopoiesis, while inhibiting adipogenesis and myelopoiesis. Impaired bone formation and defective hematopoiesis were observed when O-GlcNAc transferase (OGT) was ablated in BMSCs.
Review
Cell Biology
Olivia Arnold, Karina Barbosa, Aniruddha J. Deshpande, Nan Zhu
Summary: DOT1L plays a crucial role in normal and malignant hematopoiesis, and its aberrant activity is implicated in the development of hematopoietic malignancies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Immunology
Diannita Kwang, Gavin Tjin, Louise E. Purton
Summary: B lymphopoiesis in adult mice involves interactions with non-hematopoietic cells in the bone marrow and spleen, which provide signals for migration, maturation, and survival. Conditional knockout and transgenic mouse models have revealed the roles of distinct microenvironment cell types in regulating B lymphopoiesis. Single cell RNA-seq studies have also identified clusters of stromal cell types in these organs, aiding in the identification of key regulators of B lymphopoiesis.
IMMUNOLOGICAL REVIEWS
(2021)
Article
Hematology
Chiara Pirillo, Flora Birch, Floriane S. Tissot, Sara Gonzalez Anton, Myriam Haltalli, Valentina Tini, Isabella Kong, Ben Partridge, Constandina Pospori, Karen Keeshan, Salvatore Santamaria, Edwin Hawkins, Brunangelo Falini, Andrea Marra, Delfim Duarte, Chiu Fan Lee, Edward Roberts, Cristina Lo Celso
Summary: By studying an experimental model of AML, it was found that AML may directly affect healthy cells through damaged blood vessels. By inhibiting the activity of matrix metalloproteinases (MMPs), the spread and invasion of AML can be reduced, the retention of healthy hematopoietic stem cells (HSPCs) in the bone marrow can be increased, and patient survival can be extended. This suggests that MMP inhibition could be a promising complementary therapy.
Article
Endocrinology & Metabolism
Takaharu Kimura, Cristina Panaroni, Erinn B. Rankin, Louise E. Purton, Joy Y. Wu
Summary: PTH1R signaling in osteoprogenitors affects multiple maturing hematopoietic cell populations, potentially through regulation of cell adhesion molecules and chemokine expression that impact cell trafficking.
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Article
Multidisciplinary Sciences
Luming Zhou, Guiping Kong, Ilaria Palmisano, Maria Teresa Cencioni, Matt Danzi, Francesco De Virgiliis, Jessica S. Chadwick, Greg Crawford, Zicheng Yu, Fred De Winter, Vance Lemmon, John Bixby, Radhika Puttagunta, Joost Verhaagen, Constandina Pospori, Cristina Lo Celso, Jessica Strid, Marina Botto, Simone Di Giovanni
Summary: Aging is associated with increased prevalence of axonal injuries, and the underlying mechanisms remain unclear. This study found that T cell signaling is enriched in mice before and after sciatic nerve injury (SNI), and this signaling promotes immune cell recruitment and axonal injury through the activation of specific proteins. Inhibition of T cell recruitment facilitates axonal regeneration.
Article
Biochemistry & Molecular Biology
Nataliya Migulina, Gavin Tjin, Alen Faiz, Theo Borghuis, Fenghua Zhao, Hans J. Kaper, Marit Metzlar, Eline van Dijk, Prashant K. Sharma, Wim Timens, Reinoud Gosens, Corry-Anke Brandsma, Janette K. Burgess
Summary: This study investigated the effects of smoking and COPD on LOs gene and protein expression in the airways and found that LOs alterations may be related to smoking and contribute to impaired airway function in COPD, providing potential novel targets for prevention or treatment of small airways changes in COPD.
Article
Hematology
Louise E. Purton
Summary: This article provides an update on the key functional properties of hematopoietic stem cells and multipotent progenitor cells in adult mice, as well as their hierarchical structure. Research has revealed the existence of different types of HSC and MPP cells in adults, challenging our understanding of the hierarchy of hematopoietic cells.
EXPERIMENTAL HEMATOLOGY
(2022)
Article
Multidisciplinary Sciences
Benjamin Partridge, Sara Gonzalez Anton, Reema Khorshed, George Adams, Constandina Pospori, Cristina Lo Celso, Chiu Fan Lee
Summary: Multi-potent progenitor cells play a key role in hematopoiesis by migrating in and out of different niches to determine their fate. Our analysis of experimental data and the use of a cell motion model revealed that these cells display transient super-diffusion, highlighting the importance of motility in early hematopoietic progenitor function.
Article
Multidisciplinary Sciences
Laura Mosteo, Joana Reis, Lidia Rocha, Marta Lopes, Delfim Duarte
Summary: This article describes a method for phenotypic analysis of murine bone marrow hematopoietic stem and progenitor cells (HSPCs) and stromal niche populations through flow cytometry, to study hematopoiesis. The method provides detailed steps for enriching bone marrow cells in endosteal and central bone marrow fractions, as well as appropriate gating strategies to identify endothelial cells and mesenchymal stem cells involved in HSPC regulation.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2022)
Editorial Material
Hematology
Delfim Duarte, Sergio Chacim
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Cell Biology
Katyayanee Neopane, Natalie Kozlov, Florentina Negoita, Lisa Murray-Segal, Robert Brink, Ashfaqul Hoque, Ashley J. Ovens, Gavin Tjin, Luke M. McAloon, Dingyi Yu, Naomi X. Y. Ling, Matthew J. Sanders, Jonathan S. Oakhill, John W. Scott, Gregory R. Steinberg, Kim Loh, Bruce E. Kemp, Kei Sakamoto, Sandra Galic
Summary: This study demonstrates the relevance of AMPK myristoylation for cellular metabolic signaling. Non-myristoylated AMPK shows increased kinase activity and has an improved metabolic health under conditions of high-fat diet-induced obesity.
Letter
Hematology
Delfim Duarte, Jose Mario Mariz
ANNALS OF HEMATOLOGY
(2023)
Article
Oncology
Elodie Grockowiak, Claudia Korn, Justyna Rak, Veronika Lysenko, Adrien Hallou, Francesca M. Panvini, Matthew Williams, Claire Fielding, Zijian Fang, Eman Khatib-Massalha, Andres Garcia-Garcia, Juan Li, Reema A. Khorshed, Sara Gonzalez-Anton, E. Joanna Baxter, Anjali Kusumbe, Bridget S. Wilkins, Anna Green, Benjamin D. Simons, Claire N. Harrison, Anthony R. Green, Cristina Lo Celso, Alexandre P. A. Theocharides, Simon Mendez-Ferrer
Summary: Aging promotes the growth of hematopoietic stem cells (HSCs) with somatic mutations related to myeloid malignancies, such as myeloproliferative neoplasms (MPNs). Different bone marrow niches were found for HSCs in different MPN subtypes. JAK-STAT signaling regulates HSC polarity, niche interaction, and mutant cell expansion. The interactions between HSCs and niches influence the expansion rate and therapy response of cells with the same clonal hematopoiesis oncogenic driver.
Letter
Hematology
Maria P. Coutinho, Maria Jose Teles, Graca Melo, Marta Lopes, Delfim Duarte, Tiago L. Duarte, Julia Reis, Ana Claudia Martins, Jose Carlos Oliveira, Graca Porto
Article
Endocrinology & Metabolism
Celia A. Soto, Cristina Lo Celso, Louise E. Purton, Benjamin J. Frisch
Summary: The bone marrow microenvironment plays a crucial role in regulating hematopoiesis and interacting with hematologic malignancies, impacting malignant progression, chemotherapy resistance, and normal hematopoiesis. Studies supporting these interactions and challenges in this exciting research field are discussed.
Review
Endocrinology & Metabolism
Jemima E. Schadow, David Maxey, Toby O. Smith, Mikko A. J. Finnila, Sarah L. Manske, Neil A. Segal, Andy Kin On Wong, Rachel A. Davey, Tom Turmezei, Kathryn S. Stok
Summary: This study systematically reviewed the published parameters for assessing subchondral bone in human osteoarthritis using computed tomography. The study identified clinically meaningful parameter categories and emphasized the importance of quantification and standardized measurement methods for improving the evaluation of disease progression.
Article
Endocrinology & Metabolism
Lindsay L. Loundagin, Kim D. Harrison, Xuan Wei, David M. L. Cooper
Summary: This study developed new techniques to define zones of BMU activity based on the 3D morphology of remodeling spaces in rabbit cortical bone and integrated morphological data with the BMU longitudinal erosion rate (LER) to elucidate the spatial-temporal coordination of BMUs and estimate mineral apposition rate (MAR). The results showed that the manual and semi-automated methods accurately defined the zones of remodeling spaces, and these techniques have the potential to assess dynamic parameters of bone resorption and formation.
Article
Endocrinology & Metabolism
Soroush Masrouri, Farzad Esmaeili, Maryam Tohidi, Fereidoun Azizi, Farzad Hadaegh
Summary: This study examined the association between estimated glomerular filtration rate (eGFR) decline and fracture incidence. The results showed that rapid kidney function decline (RKFD) can increase the incidence of fractures among the general population.
Article
Endocrinology & Metabolism
Steven J. Meas, Gabriella M. Daire, Michael A. Friedman, Rachel Denapoli, Preetam Ghosh, Joshua N. Farr, Henry J. Donahue
Summary: Age- and disuse-related bone loss both lead to decreases in bone mineral density, cortical thickness, and trabecular thickness and connectivity. It is important to experimentally compare these two mechanisms at a structural and transcriptomic level to better understand their similarities and differences. This study compares the effects of hindlimb unloading and aging on bone microarchitecture and gene expression in mice, finding that while both induce similar changes, aging has a greater impact on the transcriptome and tissue level.
Correction
Endocrinology & Metabolism
Masaru Matsuoka, Sho Tsukamoto, Yuta Orihara, Rieko Kawamura, Mai Kuratani, Nobuhiko Haga, Kenji Ikebuchi, Takenobu Katagiri
Article
Endocrinology & Metabolism
Rachel Kohler, Amy Creecy, David R. Williams, Matthew R. Allen, Joseph M. Wallace
Summary: Osteogenesis imperfecta is a hereditary bone disease that weakens bones and increase fracture risk. Current interventions mainly focus on increasing bone mass, but the compromised tissue-level material properties are not addressed. A study found that a RAL analog could reduce fracture risk, but further development is needed for optimal results in patients with osteogenesis imperfecta.
Article
Endocrinology & Metabolism
So Jeong Park, Eunhye Ji, Hyun Ju Yoo, Kyunggon Kim, Sunghwan Ji, Ji Yeon Baek, Jin Young Lee, Hee-Won Jung, Il-Young Jang, Eunju Lee, Namki Hong, Beom-Jun Kim
Summary: The study analyzed the relationship between serum lumican levels and osteosarcopenia in older adults, showing that older adults with osteosarcopenia had lower serum lumican levels. Lower serum lumican levels were associated with reduced bone mass and grip strength, indicating that lumican levels could be used as a biomarker for assessing the risk of osteosarcopenia, osteoporosis, or sarcopenia in older adults.
Article
Endocrinology & Metabolism
Michael B. Chavez, Michelle H. Tan, Tamara N. Kolli, Natalie L. Andras, Brian L. Foster
Summary: This study revealed the complex mechanisms by which disabling BSP functional domains led to profound and distinct changes in cementoblast cell functions, including dysregulated gene expression and reduced mineralization.
Article
Endocrinology & Metabolism
Julien Seiller, Blandine Merle, Romain Fort, Emilie Virot, Solene Poutrel, Giovanna Cannas, Arnaud Hot, Roland Chapurlat
Summary: The purpose of this study was to assess the prevalence of bone fragility in sickle cell patients and to evaluate the potential risk factors and associated complications.
Article
Endocrinology & Metabolism
Chirantap Oza, Anuradha Khadilkar, Pranay Goel, Madhura Karguppikar, Nikhil Shah, Nikhil Lohiya, Shruti Mondkar, Prashant Patil, Hemchand Prasad, Ankita Maheshwari, Dipali Ladkat, Neha Kajale, Chidvilas More, Devarati Khurjekar, Vaman Khadilkar
Summary: This study revealed that BoneXpert (BX) can be used for accurate assessment of bone age and screening of bone health in Indian children and youth with type-1 diabetes (T1D). 51.5% of T1D subjects showed significantly decreased metacarpal index (MCI). Height, Tanner stage, and vitamin D concentrations were positively correlated with MCI, while HbA1c and disease duration were negatively correlated with MCI.
Article
Endocrinology & Metabolism
Mariam R. Farman, Catherine Rehder, Theodora Malli, Cheryl Rockman-Greenberg, Kathryn Dahir, Gabriel Angel Martos-Moreno, Agnes Linglart, Keiichi Ozono, Lothar Seefried, Guillermo del Angel, Gerald Webersinke, Francesca Barbazza, Lisa K. John, Sewmi M. A. Delana Mudiyanselage, Florian Hoegler, Erica Burner Nading, Erin Huggins, Eric T. Rush, Ahmed El-Gazzar, Priya S. Kishnani, Wolfgang Hoegler
Summary: The ALPL gene variant database serves as an archive for interpreting the clinical significance of ALPL gene variants, facilitating the reclassification of VUS and continuous updates. The project establishes an international expert consortium, providing a multidisciplinary collaboration framework to improve genetic counseling and medical decision-making for HPP patients.
Article
Endocrinology & Metabolism
Giovanni Adami, Davide Gatti, Maurizio Rossini, Alessandro Giollo, Matteo Gatti, Francesco Bertoldo, Eugenia Bertoldo, Amy S. Mudano, Kenneth G. Saag, Ombretta Viapiana, Angelo Fassio
Summary: Certain diseases requiring glucocorticoids are independently associated with an increased risk of fractures. Chronic obstructive pulmonary disease (COPD) and neurological diseases are associated with both vertebral and non-vertebral fracture risk, while rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) are only associated with non-vertebral fractures.
Article
Endocrinology & Metabolism
Frank C. Ko, Rong Xie, Brandon Willis, Zoe G. Herdman, Bryan A. Dulion, Hoomin Lee, Chun-do Oh, Di Chen, D. Rick Sumner
Summary: Intramembranous bone regeneration is important in joint and tooth replacement, but its underlying mechanisms are not well understood. This study found that increased periostin gene expression preceded increases in osteogenic genes during bone regeneration. Using a genetic mouse model, the researchers discovered that cells transiently expressing periostin played a critical role in intramedullary intramembranous bone regeneration.
Article
Endocrinology & Metabolism
T. Savikangas, T. H. Suominen, M. Alen, T. Rantalainen, S. Sipila
Summary: Regular exercise, especially high-intensity physical activity, can help slow down age-related bone loss and prevent a decline in femoral neck bone mineral density.
Article
Endocrinology & Metabolism
Mishaela R. Rubin, Ruban Dhaliwal
Summary: The increased risk of fractures observed in adults with type 1 diabetes (T1D) cannot be solely explained by modest decreases in areal bone mineral density (BMD). Accumulation of advanced glycation endproducts (AGEs) in bone has been suggested as a possible cause for the increased bone fragility in diabetes. Although the evidence linking AGEs and fractures in individuals with T1D is limited, recent data show that AGEs, as measured by skin intrinsic fluorescence, are a risk factor for lower BMD in T1D. Further research is needed to determine if there is a causal relationship between fractures and AGEs in T1D. If confirmed, this could lead to interventions that can reduce AGE accumulation and ultimately reduce fractures in T1D patients.