Cell & Tissue Engineering

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Article Cell & Tissue Engineering

SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids

Jitske Jansen, Katharina C. Reimer, James S. Nagai, Finny S. Varghese, Gijs J. Overheul, Marit de Beer, Rona Roverts, Deniz Daviran, Liline A. S. Fermin, Brigith Willemsen, Marcel Beukenboom, Sonja Djudjaj, Saskia von Stillfried, Larissa E. van Eijk, Mirjam Mastik, Marian Bulthuis, Wilfred den Dunnen, Harry van Goor, Jan-Luuk Hillebrands, Sergio H. Triana, Theodore Alexandrov, Marie-Cherelle Timm, Bartholomeus T. van den Berge, Martijn van den Broek, Quincy Nlandu, Joelle Heijnert, Eric M. J. Bindels, Remco M. Hoogenboezem, Fieke Mooren, Christoph Kuppe, Pascal Miesen, Katrien Grunberg, Ties Ijzermans, Eric J. Steenbergen, Jan Czogalla, Michiel F. Schreuder, Nico Sommerdijk, Anat Akiva, Peter Boor, Victor G. Puelles, Juergen Floege, Tobias B. Huber, Ronald P. van Rij, Ivan G. Costa, Rebekka K. Schneider, Bart Smeets, Rafael Kramann

Summary: The study found that SARS-CoV-2 can directly infect kidney cells, leading to cell injury and fibrosis, causing kidney failure. Inhibitors can alleviate the infection.

CELL STEM CELL (2022)

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Review Cell & Tissue Engineering

Recent advances in smart stimuli-responsive biomaterials for bone therapeutics and regeneration

Hongpu Wei, Jinjie Cui, Kaili Lin, Jing Xie, Xudong Wang

Summary: Bone defects combined with tumors, infections, or other bone diseases are challenging in clinical practice. To address this problem, researchers have designed various implantable biomaterials that can play a role in bone therapy and regeneration. External physical stimuli, endogenous disease microenvironments, and multiple integrated strategies can improve bone tissue therapy and regeneration.

BONE RESEARCH (2022)

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Article Cell & Tissue Engineering

The blood-brain barrier is dysregulated in COVID-19 and serves as a CNS route for SARS-CoV-2

Susanne Krasemann, Undine Haferkamp, Susanne Pfefferle, Marcel S. Woo, Fabian Heinrich, Michaela Schweizer, Antje Appelt-Menzel, Alevtina Cubukova, Janica Barenberg, Jennifer Leu, Kristin Hartmann, Edda Thies, Jessica Lisa Littau, Diego Sepulveda-Falla, Liang Zhang, Kathy Ton, Yan Liang, Jakob Matschke, Franz Ricklefs, Thomas Sauvigny, Jan Sperhake, Antonia Fitzek, Anna Gerhartl, Andreas Brachner, Nina Geiger, Eva-Maria Koenig, Jochen Bodem, Soren Franzenburg, Andre Franke, Stefan Moese, Franz-Josef Mueller, Gerd Geisslinger, Carsten Claussen, Aimo Kannt, Andrea Zaliani, Philip Gribbon, Benjamin Ondruschka, Winfried Neuhaus, Manuel A. Friese, Markus Glatzel, Ole Pless

Summary: Neurological complications are common in COVID-19. This study reveals that SARS-CoV-2 can enter the brain through the blood-brain barrier and cause increased interferon signaling. In vitro experiments show that SARS-CoV-2 can infect BCECs and replicate, with the virus being transported across the barrier. This process can be inhibited by specific antibodies or inhibitors.

STEM CELL REPORTS (2022)

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Review Cell & Tissue Engineering

The application of mesenchymal stromal cells (MSCs) and their derivative exosome in skin wound healing: a comprehensive review

Donghui Bian, Yan Wu, Guodong Song, Ramyar Azizi, Amir Zamani

Summary: Recently, mesenchymal stromal cells (MSCs) and their exosomes have become crucial tools in tissue engineering and regenerative medicine. MSCs have the ability to establish skin cells and suppress inflammation, while their exosomes can support wound healing and skin regeneration by delivering functional cargos from MSCs to target cells. The advantages of exosome therapy include reduced risk of tumor formation and lower immunogenicity.

STEM CELL RESEARCH & THERAPY (2022)

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Editorial Material Cell & Tissue Engineering

A Conversation on Artificial Intelligence, Chatbots, and Plagiarism in Higher Education

Michael R. King

CELLULAR AND MOLECULAR BIOENGINEERING (2023)

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Review Cell & Tissue Engineering

Mechanical regulation of bone remodeling

Lijun Wang, Xiuling You, Lingli Zhang, Changqing Zhang, Weiguo Zou

Summary: Bone remodeling is a lifelong process that involves a balance between bone formation and resorption. Mechanical forces play a crucial role in maintaining bone homeostasis, and loss of mechanical stimulation can weaken the bone structure and increase the risk of fracture. Understanding the mechanisms by which the body senses and transduces mechanical forces is important for studying bone disorders and developing strategies for skeletal rejuvenation.

BONE RESEARCH (2022)

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Article Cell & Tissue Engineering

Clinical Trials Based on Mesenchymal Stromal Cells are Exponentially Increasing: Where are We in Recent Years?

Umberto Galderisi, Gianfranco Peluso, Giovanni Di Bernardo

Summary: Mesenchymal stromal cells (MSCs) have been widely utilized in clinical trials, particularly for treating cardiovascular diseases, GvHD, and brain and neurological disorders. Despite some successes, there have also been failures in MSC-based therapies. Integrating data from unsuccessful studies may aid in developing new therapeutic strategies to improve clinical outcomes.

STEM CELL REVIEWS AND REPORTS (2022)

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Article Cell & Tissue Engineering

Hif-1a suppresses ROS-induced proliferation of cardiac fibroblasts following myocardial infarction

Vaibhao Janbandhu, Vikram Tallapragada, Ralph Patrick, Yanzhen Li, Dhanushi Abeygunawardena, David T. Humphreys, Ella M. M. A. Martin, Alexander O. Ward, Osvaldo Contreras, Nona Farbehi, Ernestene Yao, Junjie Du, Sally L. Dunwoodie, Nenad Bursac, Richard P. Harvey

Summary: Cardiac fibroblasts (CFs) and mesenchymal progenitors are more hypoxic and express more HIF-1a, leading to increased glycolytic metabolism. CF-specific deletion of Hif-1a results in increased mesenchymal progenitors and CF activation in uninjured hearts, but increased CF proliferation and excessive scarring after myocardial infarction. CF proliferation is associated with higher reactive oxygen species (ROS).

CELL STEM CELL (2022)

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Article Cell & Tissue Engineering

Inflammatory exposure drives long-lived impairment of hematopoietic stem cell self-renewal activity and accelerated aging

Ruzhica Bogeska, Ana-Matea Mikecin, Paul Kaschutnig, Malak Fawaz, Marleen Buechler-Schaeff, Duy Le, Miguel Ganuza, Angelika Vollmer, Stella Paffenholz, Noboru Asada, Esther Rodriguez-Correa, Felix Frauhammer, Florian Buettner, Melanie Ball, Julia Knoch, Sina Staeble, Dagmar Walter, Amelie Petri, Martha J. Carreno-Gonzalez, Vinona Wagner, Benedikt Brors, Simon Haas, Daniel B. Lipka, Marieke A. G. Essers, Vivienn Weru, Tim Holland-Letz, Jan-Philipp Mallm, Karsten Rippe, Stephan Kraemer, Matthias Schlesner, Shannon McKinney Freeman, Maria Carolina Florian, Katherine Y. King, Paul S. Frenette, Michael A. Rieger, Michael D. Milsom

Summary: Infection or inflammation may lead to irreversible depletion of functional hematopoietic stem cells, resulting in long-term effects on tissue maintenance and regeneration.

CELL STEM CELL (2022)

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Review Cell & Tissue Engineering

Mesenchymal Stem/Stromal Cell Senescence: Hallmarks, Mechanisms, and Combating Strategies

Zhijie Weng, Yigan Wang, Takehito Ouchi, Hanghang Liu, Xianghe Qiao, Chenzhou Wu, Zhihe Zhao, Longjiang Li, Bo Li

Summary: Aging is a complex process that leads to a decline in normal physiological functions, resulting in increased frailty, mortality, and chronic diseases such as skeletal, cardiovascular, and cognitive disorders. Stem cell aging, particularly mesenchymal stem/stromal cell (MSC) aging, is a significant theory in understanding organismal aging. MSCs have been considered as an ideal source for stem cell-based anti-aging therapy due to their clinical characteristics, but their therapeutic applications are limited by functional deterioration and loss of stemness associated with age or extended culture. Despite the unclear understanding of the processes behind MSC senescence, progress has been made in elucidating the phenotypic changes and possible mechanisms driving MSC senescence. This review aims to summarize current knowledge on aging MSCs, including morphological, biological, and stem-cell marker alterations, as well as the cellular and molecular mechanisms of MSC senescence, recent progress in rejuvenating senescent MSCs, and the interplay between aging MSCs and their niche.

STEM CELLS TRANSLATIONAL MEDICINE (2022)

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Article Cell & Tissue Engineering

Human embryonic genome activation initiates at the one-cell stage

Maki Asami, Brian Y. H. Lam, Marcella K. Ma, Kara Rainbow, Stefanie Braun, Matthew D. VerMilyea, Giles S. H. Yeo, Anthony C. F. Perry

Summary: Human embryonic transcription initiates at the one-cell stage, sooner than previously thought, with both upregulation and downregulation of genes impacting early development processes.

CELL STEM CELL (2022)

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Article Cell & Tissue Engineering

The Potential Use of Mesenchymal Stem Cells and Their Derived Exosomes for Orthopedic Diseases Treatment

Kosar Malekpour, Ali Hazrati, Marziah Zahar, Alexander Markov, Angelina Olegovna Zekiy, Jamshid Gholizadeh Navashenaq, Leila Roshangar, Majid Ahmadi

Summary: Musculoskeletal disorders (MSDs) can affect muscles, bones, and joints, with a higher prevalence in the elderly. Multipotent stem cells (MSCs) have been widely studied in regenerative medicine due to their ability to differentiate into various cells and their characteristics such as immunomodulatory properties and production of extracellular vesicles. MSCs and their exosomes play a crucial role in repairing dense connective tissues such as tendons, cartilage, intervertebral discs, bone fractures, and osteoporosis treatment.

STEM CELL REVIEWS AND REPORTS (2022)

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Review Cell & Tissue Engineering

Wound healing, fibroblast heterogeneity, and fibrosis

Heather E. Talbott, Shamik Mascharak, Michelle Griffin, Derrick C. Wan, Michael T. Longaker

Summary: Fibroblasts are important cells in tissue repair and fibrosis, but our understanding of the mechanisms by which they contribute to extracellular matrix deposition and remodeling is limited. This review discusses the current state of fibroblast biology and heterogeneity, with a focus on their role in skin wound repair, and evaluates the limitations of existing techniques and knowledge. The review highlights the critical functions of fibroblasts, a often overlooked cell type, in wound repair and other processes.

CELL STEM CELL (2022)

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Article Cell & Tissue Engineering

Targeting ferroptosis suppresses osteocyte glucolipotoxicity and alleviates diabetic osteoporosis

Yiqi Yang, Yixuan Lin, Minqi Wang, Kai Yuan, Qishan Wang, Pei Mu, Jingke Du, Zhifeng Yu, Shengbing Yang, Kai Huang, Yugang Wang, Hanjun Li, Tingting Tang

Summary: Diabetic osteoporosis (DOP) is characterized by osteocyte death through iron-dependent programmed cell death called ferroptosis. The diabetic microenvironment enhances osteocyte ferroptosis by promoting lipid peroxidation, iron overload, and aberrant activation of the ferroptosis pathway. Heme oxygenase-1 (HO-1) is upregulated in ferroptotic osteocytes in DOP, and its expression is controlled by the interaction between the transcription factors NRF2 and c-JUN. Targeting ferroptosis or HO-1 effectively rescues osteocyte death in DOP and improves trabecular deterioration.

BONE RESEARCH (2022)

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Article Cell & Tissue Engineering

Improved MSC Minimal Criteria to Maximize Patient Safety: A Call to Embrace Tissue Factor and Hemocompatibility Assessment of MSC Products

Guido Moll, James A. Ankrum, Scott D. Olson, Jan A. Nolta

Summary: The number and types of mesenchymal stromal/stem cell (MSC) therapeutics and clinical applications have greatly increased, but there is also a risk of poorly regulated Stem Cell Clinics offering unproven interventions. It is important to critically evaluate the identity and suitability of MSC products for safe intravascular administration.

STEM CELLS TRANSLATIONAL MEDICINE (2022)

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Article Cell & Tissue Engineering

Multi-omic analysis reveals divergent molecular events in scarring and regenerative wound healing

Shamik Mascharak, Heather E. Talbott, Michael Januszyk, Michelle Griffin, Kellen Chen, Michael F. Davitt, Janos Demeter, Dominic Henn, Clark A. Bonham, Deshka S. Foster, Nancie Mooney, Ran Cheng, Peter K. Jackson, Derrick C. Wan, Geoffrey C. Gurtner, Michael T. Longaker

Summary: In this study, we investigated the molecular events driving skin wound cells toward scarring or regenerative fates. By integrating data from single-cell RNA sequencing, proteomics, and tissue analysis, we revealed the molecular trajectories of fibrosis and regeneration during wound healing. Disrupting YAP mechanotransduction was found to activate Trps1 and Wnt signaling in fibroblasts, leading to regenerative repair. Our findings provide a multi-omic map of wound regeneration and have therapeutic implications for pathologic fibroses.

CELL STEM CELL (2022)

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Article Cell & Tissue Engineering

3D-organoid culture supports differentiation of human CAR+ iPSCs into highly functional CAR T cells

Zhiqiang Wang, Helen P. McWilliams-Koeppen, Hernan Reza, Julie R. Ostberg, Wuyang Chen, Xiuli Wang, Christian Huynh, Vibhuti Vyas, Wen-Chung Chang, Renate Starr, Jamie R. Wagner, Brenda Aguilar, Xin Yang, Xiwei Wu, Jinhui Wang, Wei Chen, Ellery Koelker-Wolfe, Christopher S. Seet, Amelie Montel-Hagen, Gay M. Crooks, Stephen J. Forman, Christine E. Brown

Summary: Generating highly functional CAR T cells from iPSCs is a promising off-the-shelf manufacturing strategy. Our study demonstrates a feasible approach to differentiate iPSCs into CAR T cells with conventional characteristics, showing comparable antigen recognition and anti-tumor activity to conventional CAR T cells.

CELL STEM CELL (2022)

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Article Cell & Tissue Engineering

Nebulized exosomes derived from allogenic adipose tissue mesenchymal stromal cells in patients with severe COVID-19: a pilot study

Ying-Gang Zhu, Meng-meng Shi, Antoine Monsel, Cheng-xiang Dai, Xuan Dong, Hong Shen, Su-ke Li, Jing Chang, Cui-li Xu, Ping Li, Jing Wang, Mei-ping Shen, Cheng-jie Ren, De-chang Chen, Jie-Ming Qu

Summary: This study explores the safety and efficacy of aerosol inhalation of exosomes derived from human adipose-derived MSCs (haMSC-Exos) in COVID-19 patients. The results show that a consecutive 5-day inhalation dose of haMSC-Exos is feasible and well tolerated, with no evidence of adverse events and CT imaging improvement within 7 days.

STEM CELL RESEARCH & THERAPY (2022)

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Article Cell & Tissue Engineering

Dissecting the molecular basis of human interneuron migration in forebrain assembloids from Timothy syndrome

Fikri Birey, Min-Yin Li, Aaron Gordon, Mayuri Thete, Alfredo M. Valencia, Omer Revah, Anca M. Pasca, Daniel H. Geschwind, Sergiu P. Pasca

Summary: In this study, it was found that the role of L-type calcium channel in neurodevelopmental diseases is complex, as it can regulate the saltation length and frequency of interneuron migration. Inhibition of GABA-A receptors can restore the defect in migration frequency, while modulation of actomyosin and myosin light chain phosphorylation can improve the defect in saltation length.

CELL STEM CELL (2022)

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Article Cell & Tissue Engineering

Enteric glial cell heterogeneity regulates intestinal stem cell niches

Meryem B. Baghdadi, Arshad Ayyaz, Sabrina Coquenlorge, Bonnie Chu, Sandeep Kumar, Catherine Streutker, Jeffrey L. Wrana, Tae-Hee Kim

Summary: This study investigates the heterogeneity and regulation of enteric glial cells (EGCs) in the intestine during homeostasis and chronic inflammatory bowel disease. A specific subset of glial cells, expressing GFAP, is found to regulate the repair potential of intestinal stem cells (ISCs) through the expression of WNT ligands. The dynamically regulated heterogeneity of EGCs is revealed to be a key part of the intestinal stem cell niche in regeneration and disease.

CELL STEM CELL (2022)

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