Article
Biochemistry & Molecular Biology
Ximena Bonilla, Ana Milena Lara, Manuela Llano-Leon, David A. Lopez-Gonzalez, David G. Hernandez-Mejia, Rosa Helena Bustos, Bernardo Camacho-Rodriguez, Ana-Maria Perdomo-Arciniegas
Summary: Umbilical cord blood is an important source of hematopoietic stem and progenitor cells, and recent research has focused on developing ex vivo expansion strategies for these cells. Co-culturing the cells with specific mesenchymal stromal cells has been found to significantly increase their cellular dose and regulate their proliferation capacity. Additionally, the secretory profile of umbilical cord blood-derived cells closely resembles that of bone marrow-derived cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Stefania Crippa, Ludovica Santi, Margherita Berti, Giada De Ponti, Maria Ester Bernardo
Summary: The human organism requires the production of approximately 1 trillion new blood cells per day through hematopoiesis in the bone marrow, regulated by the BM microenvironment and HSPCs. The BM niche, defined by interactions between HSPCs and non-hematopoietic cells, controls HSPC maintenance and orchestrates hematopoiesis according to the body's needs. Mesenchymal stromal cells (MSCs) play a key role in the BM niche by regulating HSPC homeostasis and impacting the outcome of hematopoietic stem cell transplantation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell & Tissue Engineering
Sara Bucar, Andre Dargen de Matos Branco, Marcia F. Mata, Joao Coutinho Milhano, Iris Caramalho, Joaquim M. S. Cabral, Ana Fernandes-Platzgummer, Claudia L. da Silva
Summary: The study compared the capacity of MSC from different sources to expand UCB CD34(+) cells ex vivo, with AT-derived MSC showing superior expansion potential and maintenance of primitive cells. UCM-derived MSC demonstrated inferior hematopoietic supportive capacity compared to MSC from adult tissues. Further research is needed to determine the impact of HPL on the hematopoietic supportive capacity of MSC.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Cell & Tissue Engineering
Valentina Orticelli, Andrea Papait, Elsa Vertua, Patrizia Bonassi Signoroni, Pietro Romele, Lorena Di Pietro, Marta Magatti, Luciana Teofili, Antonietta Rosa Silini, Ornella Parolini
Summary: This study investigated the potential of human term placenta-derived amniotic membrane MSCs (hAMSC) to support the ex vivo expansion of HSC and progenitor cells. The results suggest that hAMSCs are a valuable alternative to BM-MSC for enhancing the proliferation and maintaining stemness of CB-HSC, and can improve the colony forming unit ability and long-term culture initiating cells ability, addressing the need for high HSC content in CB units available for transplantation.
STEM CELLS TRANSLATIONAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Fatima Aerts-Kaya, Emine Kilic, Sevil Kose, Gozde Aydin, Ilgin Cagnan, Baris Kuskonmaz, Duygu Uckan-Cetinkaya
Summary: This study investigated the effects of G-CSF treatment on the hematopoietic BM microenvironment in healthy pediatric donors. Results showed that G-CSF can expand HSPC and MSC numbers and modify local CK and GF levels, indicating a significant impact on the BM niche.
Article
Medicine, Research & Experimental
L. B. Buravkova, M. Ezdakova, I. Andrianova, A. N. Gornostaeva, P. Bobyleva, E. R. Andreeva
Summary: The study demonstrated that during ex vivo expansion, cord blood hematopoietic stem progenitor cells (cbHSPCs) can influence the functional state of mesenchymal stromal cells (MSCs), leading to the formation of early stromal progenitors with a bipotential osteo-adipogenic profile. The joint coculture resulted in a specific hematopoiesis-supportive environment, with the expression of certain MSC genes upregulated and a balance of myeloid regulators maintained. Short-term osteoinduction prior to coculture enhanced the development of a bipotential profile, indicating a more committed state of cbHSPCs.
Article
Cell Biology
Juan Gao, Shuaibing Hou, Shengnan Yuan, Yuxia Wang, Yanan Gao, Xiaolu Sun, Weili Wang, Yajing Chu, Yuan Zhou, Xiaoming Feng, Hongbo R. Luo, Tao Cheng, Jun Shi, Weiping Yuan, Xiaomin Wang
Summary: Research shows that Rheb1-deficiency in neutrophils can remodel the bone marrow environment and induce HSC expansion, possibly by impairing their ability to secrete IL-6, affecting the production of SCF by MSCs, and promoting HSC proliferation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Dentistry, Oral Surgery & Medicine
L. Yao, F. Li, C. Yu, H. Wang, Y. Wang, L. Ye, F. Yu
Summary: The influence of chronological and replicative senescence on CD51(+)/PDGFR-alpha(+) hDPSCs was investigated using various experimental methods. Chronological senescence led to decreased CD51(+)/PDGFR-alpha(+) hDPSCs, impaired self-renewal, and higher ossificatory differentiation. Replicative senescence resulted in decreased CD51 expression, upregulated PDGFR-alpha expression, and weakened self-renewal and osteogenic differentiation. These findings highlight the distinct outcomes and core dysfunction of chronological and replicative senescence in CD51(+)/PDGFR-alpha(+) hDPSCs.
JOURNAL OF DENTAL RESEARCH
(2023)
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.
Article
Cell & Tissue Engineering
Zhengqi Wang, Grace Emmel, Hong Seo Lim, Wandi Zhu, Astrid Kosters, Eliver E. B. Ghosn, Peng Qiu, Kevin D. Bunting
Summary: This study reveals the important role of STAT5ab gene in both hematopoietic and stromal cells, and the deletion of STAT5ab using specific Cre promoters leads to a reduction in multipotent hematopoietic progenitors. Furthermore, STAT5ab is involved in the secretion of niche factors in mesenchymal stem cells and the differentiation priming of hematopoietic stem cells.
Article
Multidisciplinary Sciences
Wendi Guo, Colleen Wu
Summary: Currently, there is a lack of universally accepted markers for isolating skeletal stem cells (SSCs). Therefore, researchers continue to use bone marrow-derived mesenchymal stem cells (BMSCs) as a model to study SSCs and multipotent mesenchymal progenitors (MMPs). However, the common isolation procedures for BMSCs often result in a high percentage of hematopoietic cells, which can complicate data interpretation. In this study, a method using low oxygen tension or hypoxia is described to selectively eliminate CD45+ cells in BMSC cultures, reducing hematopoietic contaminants and enhancing MMPs and putative SSCs.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2023)
Article
Cell & Tissue Engineering
Carolina Rodriguez-Echeverri, Angelica Bonilla-Porras, Angel Gonzalez
Summary: Adult stem cells have therapeutic potential, but they play complex roles in the immune responses of some infectious diseases. For example, certain fungal pathogens can influence the behavior of stem cells and mesenchymal stromal cells by inducing proliferation and differentiation, thereby affecting the immune response.
STEM CELLS AND DEVELOPMENT
(2021)
Article
Genetics & Heredity
Mohadese Hashem Boroojerdi, Vahid Hosseinpour Sarmadi, Maryam Maqbool, King-Hwa Ling, Pooria Safarzadeh Kozani, Pouya Safarzadeh Kozani, Rajesh Ramasamy
Summary: This study elucidates the regulatory mechanisms of mesenchymal stem cells (MSCs) on the proliferation of hematopoietic stem cells (HSCs), providing a potential approach for obtaining larger quantities of HSCs in vitro without the need for manipulating their differentiation potential.
Article
Cell Biology
Beverly Brooks, Dominique Ebedes, Ahsan Usmani, Joaquin Vega Gonzales-Portillo, Daniel Gonzales-Portillo, Cesario Borlongan
Summary: Ischemic brain injury is a major cause of death worldwide with limited treatment options. Stem cell-based regenerative therapies, specifically mesenchymal stromal cells, show promise in stroke treatment, but further research is needed to fully understand their cell function.
Article
Biochemistry & Molecular Biology
Sanshiro Kanazawa, Hiroyuki Okada, Dan Riu, Yo Mabuchi, Chihiro Akazawa, Junichi Iwata, Kazuto Hoshi, Atsuhiko Hikita
Summary: This study demonstrates the important role of c-Mpl signal in the proliferation and differentiation ability of mesenchymal stem cells (MSCs), which are maintained through co-culture with hematopoietic stem cells (HSCs). Furthermore, the study suggests the existence of a hematopoietic-mesenchymal signal and highlights the significance of HSC state in the stability of MSC properties.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medical Laboratory Technology
Stephanie Sontag, Ledio Bocova, Wouter H. G. Hubens, Selina Nuechtern, Matthis Schnitker, Thomas Look, Kema M. Schroeder, Birgit Pluemaekers, Vithurithra Tharmapalan, Martina Wessiepe, Thomas Kraus, Jan Kramer, Lothar Rink, Steffen Koschmieder, Wolfgang Wagner
Summary: The study further optimized and validated targeted DNAm assays for leukocyte deconvolution using blood samples from healthy donors, ring trial participants, and patients with hematological diseases. Results showed that relative leukocyte quantification correlated with conventional blood counts using pyrosequencing or ddPCR, but outliers in epigenetic leukocyte counts were observed in some patients, especially those with hematopoietic malignancies. Further optimization of assays is needed for accurate absolute quantification.
CLINICAL CHEMISTRY
(2022)
Article
Medicine, Legal
J. Becker, P. Boehme, A. Reckert, S. B. Eickhoff, B. E. Koop, J. Blum, T. Guenduez, M. Takayama, W. Wagner, S. Ritz-Timme
Summary: The study directly compared age-associated DNA methylation patterns in German and Japanese donors, finding significant differences in certain CpG sites. However, the age prediction models based on multiple robust CpG sites did not reveal relevant differences between the two populations, suggesting the need for further research to ensure high quality age estimation.
INTERNATIONAL JOURNAL OF LEGAL MEDICINE
(2022)
Article
Oncology
Elmo W. I. Neuberger, Stephanie Sontag, Alexandra Brahmer, Keito F. A. Philippi, Markus P. Radsak, Wolfgang Wagner, Perikles Simon
Summary: Physical activity leads to an increase in cell-free DNA, with the majority of this DNA originating from granulocytes, which could compromise the accuracy of liquid biopsy.
CLINICAL EPIGENETICS
(2022)
Article
Engineering, Biomedical
Roman Goetzke, Giulio Abagnale, Burcu Yesilyurt, Lucia Salz, Olivia Cypris, Philipp Glueck, Sven Liesenfelder, Kira Zeevaert, Zhiyao Ma, Ronghui Li, Ivan G. Costa, Angelika Lampert, Vivek Pachauri, Uwe Schnakenberg, Martin Zenke, Wolfgang Wagner, Mohamed H. Elsafi Mabrouk, Marcelo A. S. Toledo
Summary: Colonies of induced pluripotent stem cells (iPSCs) exhibit self-organization and transition into 3D aggregates. This transition is characterized by gradual upregulation of specific genes and the formation of embryoid bodies (EBs). The use of polydimethylsiloxane (PDMS) pillars or micro-contact printing of vitronectin plays a role in spatial confinement and the formation of controlled size EBs without enzymatic or mechanical treatment.
Article
Medicine, Legal
F. Mayer, J. Becker, C. Reinauer, P. Boehme, S. B. Eickhoff, B. Koop, T. Guenduez, J. Blum, W. Wagner, S. Ritz-Timme
Summary: This study investigates the application of age estimation based on DNA methylation in healthy children and children with growth disorders. The findings suggest that growth disorders can impact epigenetic age predictions and CpGs in genes involved in growth and development should be avoided in age prediction models for children.
INTERNATIONAL JOURNAL OF LEGAL MEDICINE
(2022)
Review
Cell Biology
Wolfgang Wagner
Summary: Recent advances in sequencing technologies have provided opportunities for the development of epigenetic biomarkers. However, only a few of them have been successfully translated into clinical practice, mostly in oncology. When designing epigenetic biomarkers, factors such as the identification of the best genomic regions, pre-analytical processing, accuracy of DNA methylation measurements, identification of confounding parameters, accreditation as a diagnostic procedure, standardized data analysis, turnaround time, and costs and customer requirements should be considered.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Juan-Felipe Perez-Correa, Vithurithra Tharmapalan, Hartmut Geiger, Wolfgang Wagner
Summary: The aging of mice can be tracked by changes in DNA methylation at specific sites in the genome. This study compared the epigenetic modifications in C57BL/6 (B6) and DBA/2J (DBA) mice using the Infinium Mouse Methylation BeadChip. It was found that there were significant differences in age-associated DNA methylation between these two commonly used inbred mouse strains, suggesting that epigenetic clocks are not interchangeable without further verification. Certain CpG islands showed hypomethylation in aging B6 mice, while hypomethylation was observed in CpG islands in aging DBA mice. Interestingly, some CpGs showed high age-correlation in both strains and were related to genes Hsf4, Prima1, Aspa, and Wnt3a. These genes also exhibited significant age-associated DNA methylation in homologous regions in humans. A targeted epigenetic clock using pyrosequencing of these four regions was established and showed high correlation with chronological age in independent cohorts of B6 (R-2 = 0.98) and DBA (R-2 = 0.91) mice.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biology
Olivia Cypris, Julia Franzen, Joana Frobel, Philipp Glueck, Chao-Chung Kuo, Stephani Schmitz, Selina Nuechtern, Martin Zenke, Wolfgang Wagner
Summary: This study investigates the role of DNMT3A in hematopoietic differentiation using human induced pluripotent stem cells (iPSCs) and finds that different exon knockouts of DNMT3A do not significantly affect differentiation efficiency. Our model system also partially recapitulates DNA methylation patterns of acute myeloid leukemia (AML) with DNMT3A mutations. These findings contribute to the understanding of clonal hematopoiesis mechanisms.
Article
Cell & Tissue Engineering
Marco Schmidt, Kira Zeevaert, Mohamed H. Elsafi Mabrouk, Roman Goetzke, Wolfgang Wagner
Summary: Quality control of induced pluripotent stem cells is challenging, and determining trilineage differentiation potential is crucial for validating their pluripotent state. In this study, GermLayerTracker, a combination of site-specific DNA methylation assays, was developed as a biomarker for early germ layer specification. Specific CG dinucleotides (CpGs) with characteristic DNA methylation patterns were identified in the pluripotent state and during differentiation into endoderm, mesoderm, and ectoderm. The GermLayerTracker can be used for quality control of pluripotent cells and to estimate lineage-specific commitment during initial differentiation events.
Review
Biochemistry & Molecular Biology
Deepika Puri, Wolfgang Wagner
Summary: Reprogramming towards pluripotency can rejuvenate cells, reversing age-associated molecular features and evading replicative senescence. However, complete reprogramming can lead to loss of cellular identity and risk of teratoma formation. Limited exposure to reprogramming factors can partially reset epigenetic ageing clocks while maintaining cellular identity. The relationship between rejuvenation and pluripotency, as well as alternative rejuvenation approaches, are discussed in this review.
Article
Engineering, Biomedical
Jose L. Gerardo-Nava, Jitske Jansen, Daniel Guenther, Laura Klasen, Anja Lena Thiebes, Bastian Niessing, Cedric Bergerbit, Anna A. Meyer, John Linkhorst, Mareike Barth, Payam Akhyari, Julia Stingl, Saskia Nagel, Thomas Stiehl, Angelika Lampert, Rudolf Leube, Matthias Wessling, Francesca Santoro, Sven Ingebrandt, Stefan Jockenhoevel, Andreas Herrmann, Horst Fischer, Wolfgang Wagner, Robert H. Schmitt, Fabian Kiessling, Rafael Kramann, Laura De Laporte
Summary: Recreating human tissues and organs in the petri dish to establish models as tools in biomedical sciences has gained momentum. Transformative materials play an important role in this evolution, as they can be programmed to direct cell behavior and fate. This paper illustrates state-of-the-art developments in in vitro tissue engineering and the challenges related to the design, production, and translation of transformative materials, emphasizing the need for convergence of different technologies to generate functional human tissue models.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Engineering, Biomedical
Prachi Desai, Anshuman Dasgupta, Alexandros Marios Sofias, Quim Pena, Robert Goestl, Ioana Slabu, Ulrich Schwaneberg, Thomas Stiehl, Wolfgang Wagner, Stefan Jockenhoevel, Julia Stingl, Rafael Kramann, Christian Trautwein, Tim H. Bruemmendorf, Fabian Kiessling, Andreas Herrmann, Twan Lammers
Summary: Drug delivery systems (DDS) control drug availability and activity to achieve a balance between therapeutic efficacy and side effects. They overcome biological barriers encountered by drug molecules and are explored for modulating host-material interfaces. This article provides an overview of barriers and interfaces encountered by DDS in different administration routes and highlights material engineering advances for improved disease treatment.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Oncology
Lucia Salz, Alexander Seitz, Daniel Schaefer, Julia Franzen, Tatjana Holzer, Carlos A. Garcia-Prieto, Iris Buerger, Olaf Hardt, Manel Esteller, Wolfgang Wagner
Summary: CAR T cell expansion during culture leads to DNA hypermethylation, which downregulates the expression of genes relevant to T cell function. This hypermethylation signature can predict cell culture time and is associated with reduced long-term survival and therapeutic outcome in CAR T cell products.
Article
Oncology
Ledio Bocova, Wouter Hubens, Cordula Engel, Steffen Koschmieder, Edgar Jost, Wolfgang Wagner
Summary: In this study, researchers demonstrate that hematopoietic stem and progenitor cells (HSPCs) can be estimated by targeted DNA methylation (DNAm) analysis. DNAm levels at specific CpG sites in the genes MYO1D, STK17A, and SP140 were found to correlate with CD34(+) cell numbers in mobilized peripheral blood and blast counts in leukemia. These epigenetic biomarkers could potentially be used to assess stem cell mobilization, HSPC harvesting, or blast count in leukemia.
CLINICAL EPIGENETICS
(2023)
Article
Pharmacology & Pharmacy
Henrike Jacobi, Margherita Vieri, Marlena Buetow, Carolina Y. Namasu, Laura Flueter, Ivan G. Costa, Tiago Maie, Katharina Lindemann-Docter, Nicolas Chatain, Fabian Beier, Michael Huber, Wolfgang Wagner, Martina Crysandt, Tim H. Bruemmendorf, Mirle Schemionek
Summary: The management of chronic myeloid leukemia (CML) has been revolutionized by tyrosine kinase inhibitors (TKIs), which can induce deep molecular responses and lead to treatment-free remission (TFR) in some patients. However, leukemic stem cells (LSCs) often persist and can cause relapse in patients attempting TKI discontinuation. This study shows that the presence of myelofibrosis (MF) at diagnosis is associated with TFR failure.
FRONTIERS IN PHARMACOLOGY
(2023)