Review
Cell Biology
Konradin F. Muskens, Caroline A. Lindemans, Mirjam E. Belderbos
Summary: GvHD is a major complication of HCT, causing severe hematopoietic dysfunction. Immune activation during GvHD damages hematopoietic stem cells and their niche in the bone marrow, leading to reduced functionality. Complications and treatments associated with HCT exacerbate hematopoietic dysfunction.
Article
Immunology
Thomas Krueger, Rebekka Wehner, Maik Herbig, Martin Kraeter, Michael Kramer, Jan Moritz Middeke, Friedrich Stoelzel, Catrin List, Katharina Egger-Heidrich, Raphael Teipel, Uta Oelschlaegel, Martin Wermke, Helena Jambor, Manja Wobus, Johannes Schetelig, Korinna Joehrens, Torsten Tonn, Julien Subburayalu, Marc Schmitz, Martin Bornhauser, Malte von Bonin
Summary: Functional impairment of the bone marrow niche, particularly a decrease in mesenchymal stromal cells (MSCs), is associated with cytopenia and graft failure after hematopoietic cell transplantation. Acute graft-versus-host disease (aGvHD) is shown to significantly reduce MSC numbers, and this reduction can be observed before clinical onset of aGvHD. The different phenotypic and functional characteristics of MSCs depending on the occurrence of aGvHD suggest that they may contribute to alloreactivity after transplantation.
FRONTIERS IN IMMUNOLOGY
(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
Cell Biology
Annamaria Aprile, Laura Raggi, Simona Bolamperti, Isabella Villa, Mariangela Storto, Gaia Morello, Sarah Marktel, Claudio Tripodo, Maria Domenica Cappellini, Irene Motta, Alessandro Rubinacci, Giuliana Ferrari
Summary: Clinical evidence suggests a relationship between blood and bone, but the underlying mechanism is not fully understood. A study using beta-thalassemia as a model found that increased fibroblast growth factor 23 (FGF23) levels in patients and mice with beta-thalassemia were induced by erythropoietin via ERK1/2 and STAT5 pathways. Inhibiting FGF23 signaling with carboxyl-terminal FGF23 peptide rescued bone defects and restored hematopoietic stem cell function in mice with beta-thalassemia. FGF23 may serve as a molecular link connecting anemia, bone, and the hematopoietic stem cell niche.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Cell Biology
Annamaria Aprile, Laura Raggi, Simona Bolamperti, Isabella Villa, Mariangela Storto, Gaia Morello, Sarah Marktel, Claudio Tripodo, Maria Domenica Cappellini, Irene Motta, Alessandro Rubinacci, Giuliana Ferrari
Summary: This study demonstrates the overproduction of fibroblast growth factor 23 (FGF23) in patients and mice with beta-thalassemia, and shows that inhibition of FGF23 signaling is a safe and effective therapeutic strategy to rescue bone defects and restore hematopoietic stem cell function. FGF23 may serve as a molecular link connecting anemia, bone, and the HSC niche.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Medicine, Research & Experimental
Erika S. Varady, L. Angel Ayala, Pauline U. Nguyen, Vanessa M. Scarfone, Alborz Karimzadeh, Cuiwen Zhou, Xiyu Chen, Scott A. Greilach, Craig M. Walsh, Matthew A. Inlay
Summary: Donor cell conditioning with the glucocorticoid fluticasone propionate (FLU) prior to transplantation increases HSC engraftment and reduces the severity and incidence of graft-versus-host disease (GvHD) in allogeneic hosts.
EMBO MOLECULAR MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Izabella Skulimowska, Justyna Sosniak, Monika Gonka, Agata Szade, Alicja Jozkowicz, Krzysztof Szade
Summary: Recent studies on hematopoietic stem cells (HSCs) have shown promising opportunities and challenges for their clinical applications. The heterogenic pool of HSCs dynamically changes with aging, involving complex interactions with the bone marrow niche. These findings may lead to overcoming current limitations in HSC transplantation and expanding the patient group that can benefit from the clinical potential of HSCs.
Review
Pharmacology & Pharmacy
Cornelia Lee-Thedieck, Peter Schertl, Gerd Klein
Summary: This review provides a comprehensive overview of the extracellular matrix (ECM) in hematopoietic stem cell (HSC) niches and highlights its importance in regulating cellular function and niche structure. The role of different classes of ECM molecules and their interactions with cells are discussed, along with the significance of matrix remodeling and biophysics in HSC niche function. The review also examines the application of current knowledge of ECM in artificial HSC niches for HSC expansion, targeted differentiation, and drug testing.
ADVANCED DRUG DELIVERY REVIEWS
(2022)
Article
Immunology
Pooja Khandelwal, Rosa F. Yeh, Louie Yu, Adam Lane, Christopher E. Dandoy, Javier El-Bietar, Stella M. Davies, Michael S. Grimley
Summary: The addition of abatacept to standard acute GVHD prophylaxis effectively reduced the incidence of severe acute GVHD in children with beta-thalassemia major undergoing HSCT, without affecting engraftment. Thalassemia-free survival was significantly higher in the abatacept group compared to the standard group.
Article
Immunology
Qianqian Wang, Xiuhua Su, Yi He, Mei Wang, Donglin Yang, Rongli Zhang, Jialin Wei, Qiaoling Ma, Weihua Zhai, Aiming Pang, Yong Huang, Sizhou Feng, Christie M. Ballantyne, Huaizhu Wu, Xiaolei Pei, Xiaoming Feng, Mingzhe Han, Erlie Jiang
Summary: Blocking CD11c inhibits T cell proliferation and differentiation into Th1 cells, playing crucial roles in aGVHD pathogenesis. CD11c deficiency alleviates aGVHD symptoms by affecting antigen presentation of DCs.
Review
Immunology
Francesca Matteini, Medhanie A. Mulaw, M. Carolina Florian
Summary: The aging of the bone marrow niche leads to declining HSC function, but certain niche structures and signals are crucial for maintaining HSC function. The use of new technical tools has revealed the impact of BM niche aging on HSCs.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biophysics
Ikegame Kazuhiro, Kaida Katsuji, Fukunaga Keiko, Osugi Yuko, Yoshihara Kyoko, Yoshihara Satoshi, Ishii Shinichi, Fujino Satoshi, Yamashita Takaya, Mayumi Azusa, Maruyama Satoshi, Teramoto Masahiro, Takayuki Inoue, Masaya Okada, Hiroya Tamaki, Hiroyasu Ogawa, Yosihiro Fujimori
Summary: The study investigated the feasibility of HLA 2-haplotype-mismatched HSCT from family donors as a potential alternative option for posttransplant relapse patients. Results showed that this treatment could be considered for second or third transplantation, although there were concerns regarding complications such as GVHD.
BONE MARROW TRANSPLANTATION
(2021)
Review
Oncology
Muhammad Umair Mushtaq, Moazzam Shahzad, Ezza Tariq, Qamar Iqbal, Sibgha Gull Chaudhary, Muhammad U. Zafar, Iqra Anwar, Nausheen Ahmed, Rajat Bansal, Anurag K. Singh, Sunil H. Abhyankar, Natalie S. Callander, Peiman Hematti, Joseph P. McGuirk
Summary: A systematic review and meta-analysis evaluated the outcomes of mismatched unrelated donor hematopoietic stem cell transplantation (MMUD-HSCT). The results showed that MMUD-HSCT had favorable treatment outcomes and an acceptable toxicity profile in patients lacking HLA-matched or haploidentical donors, thus expanding the accessibility of HSCT to underrepresented populations.
FRONTIERS IN ONCOLOGY
(2022)
Review
Chemistry, Physical
Ada Congrains, Juares Bianco, Renata G. Rosa, Rubia I. Mancuso, Sara T. O. Saad
Summary: HSC depend on signals from specialized niches for production, 2D models may hinder clinical application, and recreating bone marrow complexity may offer new therapeutic avenues.
Article
Microbiology
Shiela McCollam, James S. Lewis, Joseph Bubalo, Amber Diaz
Summary: This study aimed to evaluate the efficacy and safety of 300-mg once-monthly intravenous (IV) pentamidine prophylaxis in 702 adult allogeneic hematopoietic stem cell transplant (HSCT) patients. The results showed that IV pentamidine administration effectively prevented Pneumocystis jirovecii pneumonia (PJP), but breakthrough Nocardia and Toxoplasma infections were observed in a certain percentage of patients.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Multidisciplinary Sciences
Takashi Nishina, Yutaka Deguchi, Daisuke Ohshima, Wakami Takeda, Masato Ohtsuka, Shigeyuki Shichino, Satoshi Ueha, Soh Yamazaki, Mika Kawauchi, Eri Nakamura, Chiharu Nishiyama, Yuko Kojima, Satomi Adachi-Akahane, Mizuho Hasegawa, Mizuho Nakayama, Masanobu Oshima, Hideo Yagita, Kazutoshi Shibuya, Tetuo Mikami, Naohiro Inohara, Kouji Matsushima, Norihiro Tada, Hiroyasu Nakano
Summary: IL-11, a member of the IL-6 family of cytokines, plays a role in tumor development. IL-11(+) cells are present in murine tumor and acute colitis models and induce the activation of colonic fibroblasts and epithelial cells. IL-11(+) fibroblasts contribute to a feed-forward loop between tumor cells and fibroblasts in the tumor microenvironment, affecting the development of colitis and colon cancer.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Hiroyasu Aoki, Satoshi Ueha, Yoshiaki Nakamura, Shigeyuki Shichino, Hiromichi Nakajima, Manami Shimomura, Akihiro Sato, Tetsuya Nakatsura, Takayuki Yoshino, Kouji Matsushima
Summary: The study indicates that the overlap of T-cell clones between blood and tumor may serve as a potential biomarker to predict clinical response to PD-1 blockade and guide patient selection before treatment.
Article
Multidisciplinary Sciences
Abdouramane Camara, Alice C. Lavanant, Jun Abe, Henri Lee Desforges, Yannick O. Alexandre, Erika Girardi, Zinaida Igamberdieva, Kenichi Asano, Masato Tanaka, Thomas Hehlgans, Klaus Pfeffer, Sebastien Pfeffer, Scott N. Mueller, Jens Stein, Christopher G. Mueller
Summary: CD169+ macrophages in lymph nodes and spleen require dual signals from LT beta R and RANK for their differentiation. RANKL is necessary for the formation of their niche in lymph nodes, while splenic marginal zone stromal cells provide the source of RANKL for marginal metallophilic macrophage differentiation in the spleen. Loss of these macrophages compromises viral capture and the expansion of virus-specific CD8+ T cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Yoshiki Omatsu, Shota Aiba, Tomonori Maeta, Kei Higaki, Kazunari Aoki, Hitomi Watanabe, Gen Kondoh, Riko Nishimura, Shu Takeda, Ung-il Chung, Takashi Nagasawa
Summary: The transcription factors Runx1 and Runx2 play critical roles in the cellular niches of hematopoietic stem cells (HSCs). Lack of these transcription factors in CAR cells is associated with increased fibrosis and reduced HSCs in bone marrow. Runx1 is predominantly expressed in CAR cells and is induced by the transcription factor Foxc1, which decreases fibrotic gene expression in CAR cells.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Yasutaka Hayashi, Kimihito C. Kawabata, Yosuke Tanaka, Yasufumi Uehara, Yo Mabuchi, Koichi Murakami, Akira Nishiyama, Shigeru Kiryu, Yusuke Yoshioka, Yasunori Ota, Tatsuki Sugiyama, Keiko Mikami, Moe Tamura, Tsuyoshi Fukushima, Shuhei Asada, Reina Takeda, Yuya Kunisaki, Tomofusa Fukuyama, Kazuaki Yokoyama, Tomoyuki Uchida, Masao Hagihara, Nobuhiro Ohno, Kensuke Usuki, Arinobu Tojo, Yoshio Katayama, Susumu Goyama, Fumio Arai, Tomohiko Tamura, Takashi Nagasawa, Takahiro Ochiya, Daichi Inoue, Toshio Kitamura
Summary: Myelodysplastic syndrome (MDS) is a clonal disorder of hematopoietic stem cells (HSCs), and MDS cells perturb bone metabolism by suppressing the osteolineage differentiation of mesenchymal stromal or stem cells (MSCs), resulting in impaired support for normal hematopoiesis. This suppressive effect is reversible and mediated by extracellular vesicles (EVs) derived from MDS cells.
Article
Gastroenterology & Hepatology
Mariko Tanaka, Akiko Kunita, Makoto Yamagishi, Hiroto Katoh, Shumpei Ishikawa, Hiroyuki Yamamoto, Jun Abe, Junichi Arita, Kiyoshi Hasegawa, Tatsuhiro Shibata, Tetsuo Ushiku
Summary: This study aimed to investigate the prognostic effects, association with clinicopathologic characteristics, and potential functions of KRAS mutations in intrahepatic cholangiocarcinoma (ICC). The results showed that KRAS mutations were associated with worse overall survival and distant metastasis-free survival in ICC patients. In addition, KRAS mutations were found to affect cell growth, migration, and the expression of E-cadherin in ICC cells. The findings suggest that KRAS mutation status could be a useful predictor for the prognosis of ICC patients after surgical resection.
LIVER INTERNATIONAL
(2022)
Article
Immunology
Frank P. Assen, Jun Abe, Miroslav Hons, Robert Hauschild, Shayan Shamipour, Walter A. Kaufmann, Tommaso Costanzo, Gabriel Krens, Markus Brown, Burkhard Ludewig, Simon Hippenmeyer, Carl-Philipp Heisenberg, Wolfgang Weninger, Edouard Hannezo, Sanjiv A. Luther, Jens Stein, Michael Sixt
Summary: Researchers have characterized the biomechanics of lymph node swelling and found that different fibroblast populations mechanically control its expansion in a multitier fashion.
Article
Immunology
Petra Pfenninger, Laura Yerly, Jun Abe
Summary: CRISPR/Cas9 technology has revolutionized genetic engineering of primary cells, including CD8(+) T cells. The optimized nucleofection-based CRISPR/Cas9 genetic engineering method preserves the in vivo immune responses of naive CD8(+) T cells, but slightly impairs the expansion and survival of in vitro-activated CD8(+) T cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Juliana Barreto de Albuquerque, Lukas M. Altenburger, Jun Abe, Diego von Werdt, Stefanie Wissmann, Jose Martinez Magdaleno, David Francisco, Geert van Geest, Xenia Ficht, Matteo Iannacone, Remy Bruggmann, Christoph Mueller, Jens Stein
Summary: The study identifies mandibular lymph nodes as sentinel lymphoid organs in intercepting ingested Listeria monocytogenes. Oral uptake of Lm leads to the activation and release of antigen-specific CD8(+) T cells, contributing to rapid clearance of the pathogen. Interestingly, CD8(+) T-EFF generated in the upper GI tract lack gut-seeking phenotype compared to those generated in the lower GI tract.
SCIENCE IMMUNOLOGY
(2022)
Article
Oncology
Hiroyasu Aoki, Mikiya Tsunoda, Haru Ogiwara, Haruka Shimizu, Haruka Abe, Tatsuro Ogawa, Takaya Abe, Shigeyuki Shichino, Kouji Matsushima, Satoshi Ueha
Summary: The tumor-infiltrating T-cell repertoire is a new method for characterizing effective antitumor T-cell responses. In tumor-bearing mice treated with mono-clonal anti-programmed death-ligand 1 (PD-L1) or anti-CD4, the polyclonal fraction of the tumor-reactive T-cell repertoire, consisting of relatively minor clones, increased, which correlated with antitumor effects.
CANCER IMMUNOLOGY RESEARCH
(2023)
Article
Immunology
Diego von Werdt, Bilgi Gungor, Juliana Barreto de Albuquerque, Thomas Gruber, Daniel Zysset, Cheong K. C. Kwong Chung, Antonia Correa-Ferreira, Regina Berchtold, Nicolas Page, Mirjam Schenk, John H. Kehrl, Doron Merkler, Beat A. Imhof, Jens V. Stein, Jun Abe, Gleb Turchinovich, Daniela Finke, Adrian C. Hayday, Nadia Corazza, Christoph Mueller
Summary: Members of the Regulator of G-protein signaling (Rgs) family regulate G protein signaling by increasing the GTPase activity of G alpha protein subunits. Rgs1, a member of the Rgs family, preferentially deactivates G alpha q and G alpha i subunits, attenuating chemokine receptor-mediated immune cell trafficking. Its impact on tissue-resident T cells and immunosurveillance in barrier tissues is not fully understood.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Hematology
Ji Wu, Kenta Moriwaki, Tatsuya Asuka, Ritsuko Nakai, Satoshi Kanda, Manabu Taniguchi, Tatsuki Sugiyama, Shin-ichiro Yoshimura, Masataka Kunii, Takashi Nagasawa, Naoki Hosen, Eiji Miyoshi, Akihiro Harada
Summary: Cell polarity, represented by the asymmetric distribution of proteins and organelles, plays a significant role in various cell types. EHBP1L1, a protein located on recycling endosomes, was found to be involved in erythroblast enucleation and other cell polarity systems. Deficiency of EHBP1L1 led to defective erythroid cell development, anemic lethality, and abnormal nuclear and mitochondrial localization in skeletal muscle cells.
Review
Multidisciplinary Sciences
Kouji Matsushima, Shigeyuki Shichino, Satoshi Ueha, Shizuo Akira
Summary: Inflammation is a defense response to invading stimuli, but excessive and persistent inflammation can lead to tissue injury and organ damage. Excessive inflammation is associated with human diseases. The discovery of chemotactic cytokines in the late 1980s paved the way for understanding the molecular mechanisms of inflammation. This review provides a historical overview of chemokine research over the last 35 years.
PROCEEDINGS OF THE JAPAN ACADEMY SERIES B-PHYSICAL AND BIOLOGICAL SCIENCES
(2023)
Article
Oncology
Stefan Milutinovic, Jun Abe, Emma Jones, Inken Kelch, Kathryn Smart, Sarah N. Lauder, Michelle Somerville, Carl Ware, Andrew Godkin, Jens V. Stein, Gib Bogle, Awen Gallimore
Summary: This study examines the remodeling of specialized blood vessels called HEVs in LY LNs and tumors using three-dimensional imaging and computational tools. The analysis reveals significant cancer- and immune-driven alterations to HEV networks, with the presence of these networks within tumors distinguishing responders from nonresponders. Successful treatment response is found to depend on the development of tumor-associated HEVs and T-cell activation.
CANCER RESEARCH COMMUNICATIONS
(2022)
Article
Immunology
Hisashi Ueta, Xue-Dong Xu, Bin Yu, Yusuke Kitazawa, Enqiao Yu, Yoshiaki Hara, Miwa Morita-Nakagawa, Shu Zhou, Yasushi Sawanobori, Satoshi Ueha, Kazuhito Rokutan, Toshiya Tanaka, Nobuko Tokuda, Kouji Matsushima, Kenjiro Matsuno
Summary: Using DST-antibodies and anti-donor MHCII antibodies can suppress CD8(+) T cell-mediated liver transplant rejection by depleting donor immunogenic DCs and blocking direct or semi-direct pathways of antigen recognition. Donor MHCII-specific antibodies may serve as a selective suppressant of anti-donor immunity for clinical liver transplantation without causing cellular damage to donor MHCII-graft cells and recipient cells.
INTERNATIONAL IMMUNOLOGY
(2021)