Article
Multidisciplinary Sciences
Dominika Dziedzicka, Mukul Tewary, Alexander Keller, Laurentijn Tilleman, Laura Prochazka, Joel Ostblom, Edouard Couvreu De Deckersberg, Christina Markouli, Silvie Franck, Filip Van Nieuwerburgh, Claudia Spits, Peter W. Zandstra, Karen Sermon, Mieke Geens
Summary: Low differentiation propensity towards a targeted lineage can significantly hamper the utility of individual human pluripotent stem cell (hPSC) lines in biomedical applications. Gene expression profiling reveals that inefficient switch from self-renewal to definitive endoderm (DE) specification in hPSCs is reflected in NANOG expression dynamics. Importantly, higher WNT stimulation or inhibition of the PI3K/AKT signaling can overcome the DE commitment blockage.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Yan Li, Zhiyu Xia, Haihong Yin, Youran Dai, Feixue Li, Jianming Chen, Mengsheng Qiu, Huarong Huang
Summary: A simple and efficient method for inducing mouse embryonic stem cells into primitive endoderm cells was reported in this study, and it was found that the Wnt signaling pathway played a critical role in this process.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Cell Biology
Chenze Xu, Ali Mohsin, Yanxia Luo, Lili Xie, Yan Peng, Qizheng Wang, Waqas Ahmed, Haifeng Hang, Yingping Zhuang, Meijin Guo
Summary: In this study, non-genetically modified Sertoli-like cells were successfully induced from mouse ESCs using defined protein factors, showing similar characteristics and functionality to natural Sertoli cells. However, the efficiency of the non-GM method was still lower compared to lentiviral transduction. This work lays a foundation for the future production of non-GM Sertoli-like cells for clinical applications and fundamental theory research.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Maayan Pour, Abhishek Sampath Kumar, Naama Farag, Adriano Bolondi, Helene Kretzmer, Maria Walther, Lars Wittler, Alexander Meissner, Iftach Nachman
Summary: This study investigates the onset of definitive endoderm (DE) using a dual Bra/Sox17 reporter cell line. It reveals that Sox17 expression initiates in isolated cells within a specific temporal window in vivo, while in vitro models show that DE cells emerge from mesendoderm progenitors in a regular but spatially stochastic pattern, which is arranged by self-sorting of Sox17+ cells. The self-sorting process coincides with upregulation of E-cadherin but is not essential for DE differentiation or proliferation.
Article
Biology
Marta Perera, Silas Boye Nissen, Martin Proks, Sara Pozzi, Rita S. Monteiro, Ala Trusina, Joshua M. Brickman
Summary: The regulation of the cell cycle is closely related to cell fate choice during the differentiation of mouse embryonic stem cells. Differential regulation of the cell cycle can tip the balance between different subfractions of cells, promoting expansion of specific lineages. Furthermore, the FGF/ERK signaling pathway not only affects the heterogeneity of embryonic stem cells, but also determines the similarity in cell cycles between sister and cousin cells.
Article
Biochemistry & Molecular Biology
Daniel Olivieri, Eleonora Castelli, Yumiko K. Kawamura, Panagiotis Papasaikas, Ilya Lukonin, Melanie Rittirsch, Daniel Hess, Sebastien A. Smallwood, Michael B. Stadler, Antoine H. F. M. Peters, Joerg Betschinger
Summary: Mouse embryonic stem cells are biased towards producing embryonic endoderm rather than extraembryonic endoderm, which is regulated by transcriptional repressors Hdac3 and Dax1. Pluripotency factors Nr5a2 and Esrrb promote cell type conversion, and perturbation of the barrier extends mESC potency. This study shows that transcriptional repressors stabilize pluripotency by biasing the equilibrium between embryonic and extraembryonic lineages in mESCs.
Article
Cell Biology
Yuting Fu, Fangyuan Liu, Shuo Cao, Jia Zhang, Huizhi Wang, Baojiang Wu, Yongli Song, Shuguang Duo, Xihe Li, Siqin Bao
Summary: This study reveals that Bdh2 deficiency has no impact on pluripotency and self-renewal of ESCs, but promotes endoderm differentiation and is essential for maintaining DNA methylation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Developmental Biology
Daniel Medina-Cano, Emily K. Corrigan, Rachel A. Glenn, Mohammed T. Islam, Yuan Lin, Juliet Kim, Hyunwoo Cho, Thomas Vierbuchen
Summary: Directed differentiation of pluripotent stem cells provides a powerful model system for studying embryonic development. Current protocols for mouse PSCs require improvement, but new protocols for generating nearly pure definitive endoderm and neural organoids present potential opportunities for research.
Article
Cell Biology
Michaela Mrugala Rothova, Alexander Valentin Nielsen, Martin Proks, Yan Fung Wong, Alba Redo Riveiro, Madeleine Linneberg-Agerholm, Eyal David, Ido Amit, Ala Trusina, Joshua Mark Brickman
Summary: Using single-cell transcriptomics, researchers have studied the different pathways of cell differentiation and identified an intermediate state in which cells transition from an extra-embryonic identity to an embryonic one. This finding has important implications for understanding organ differentiation in vitro.
NATURE CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Man-Ling Zhang, Yong Jin, Li-Hua Zhao, Jia Zhang, Meng Zhou, Mei-Shuang Li, Zhi-Bao Yin, Zi-Xin Wang, Li-Xia Zhao, Xi-He Li, Rong-Feng Li
Summary: Researchers have successfully derived porcine XEN cells through a novel method, showing positive XEN markers in vivo and retaining the ability to undergo VE and PE differentiation in vitro. These cells can be stably passaged and are significant for studying porcine embryo development and differentiation pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Developmental Biology
Erik J. Vrij, Yvonne S. Scholte Op Reimer, Laury Roa Fuentes, Isabel Misteli Guerreiro, Viktoria Holzmann, Javier Frias Aldeguer, Giovanni Sestini, Bon-Kyoung Koo, Jop Kind, Clemens A. Van Blitterswijk, Nicolas C. Rivron
Summary: In this study, a partial mouse embryo model was created to explore the principles of co-development between the epiblast and extra-embryonic endoderm. The findings reveal that through reciprocal inductions and self-organization, different lineages of the embryo can autonomously progress and differentiate.
Article
Developmental Biology
Anna Yoney, Lu Bai, Ali H. Brivanlou, Eric D. Siggla
Summary: Embryogenesis is guided by a limited set of signaling pathways dynamically expressed in different places, and in vitro models of human embryos derived from hESCs allow for addressing developmental questions. WNT priming induces the expression of the SMAD2 co-factor EOMES, enabling activin-mediated ME differentiation, revealing the mechanistic basis for priming and cellular memory in early development.
Article
Developmental Biology
Anna Yoney, Lu Bai, Ali H. Brivanlou, Eric D. Siggia
Summary: Embryogenesis is guided by a limited set of signaling pathways that control the differentiation of embryonic cells to specific cell types. Recent research has found that WNT signaling primes cells for subsequent signaling responses by inducing the expression of the SMAD2 co-factor EOMES, which is sufficient to replace WNT signaling in the differentiation process.
Article
Biochemistry & Molecular Biology
Yu You, Yandi Cui, Yuting Li, Meng Zhang, Xin Wang, Junxiang Ji, Xinbao Zhang, Min Zhou, Zhonglin Zhang, Shou-Dong Ye, Xiaoxiao Wang
Summary: The study investigated the characteristics of MTA family members in human ESCs and found that knockdown of MTA2 and MTA3 expression induces differentiation. Decreased MTA2 or MTA3 gene transcript mainly leads to the emergence of mesendoderm associated markers. Addition of ID8, a specific inhibitor of DYRKs, impairs the differentiation phenotype induced by MTA2 and MTA3 reduction.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Cell & Tissue Engineering
Mohamed Gatie, Tyler T. Cooper, Reza Khazaee, Gilles A. Lajoie, Gregory M. Kelly
Summary: Metabolism plays a crucial role in embryonic development and cell differentiation. Research has found that XEN cells are sensitive to lactate and utilize lactate accumulation to promote differentiation. These findings are significant for improving the efficiency of cell reprogramming in regenerative medicine.
Article
Anatomy & Morphology
Mohammad Rabiei, Naser Kalhor, Aisan Farhadi, Sorour Ramezanpour, Yaser Tahamtani, Mahnaz Azarnia
Summary: Despite the availability of efficient pharmaceuticals for diabetes management, new drugs are needed to preserve and restore the function of pancreatic beta-cells. In this study, small molecules with potential anti-diabetic activity were tested using an in vitro screening model. Some of these molecules were found to increase the expression of genes related to insulin production and secretion, providing potential opportunities for diabetes intervention.
CELLS TISSUES ORGANS
(2023)
Article
Nanoscience & Nanotechnology
Omid Akhavan, Hossein Baharvand, Maryam Saadati, Hossein Fazli, Shiva Nemati
Summary: Ultrathin MoS2-MoO3-x heterojunction nanosheets were used as biocompatible and visible light-sensitive stimulator layers for controlled differentiation of human neural progenitor cells (hNPCs) into nervous lineages. The differentiation of hNPCs was increased on MoS2-MoO3-x due to biophysical cues and further increased on rGO/MoS2-MoO3-x due to a synergistic effect induced by the rGO. MoO3-x domains induced p-type doping in MoS2-MoO3-x, while photostimulation led to higher differentiation into glial cells. The presence of rGO in rGO/MoS2-MoO3-x promoted ultrafast electron transfer and increased neuronal differentiation of hNPCs.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Geriatrics & Gerontology
Fariba Nosrati, Johannes Grillari, Mahnaz Azarnia, Mohammad Nabiuni, Reza Moghadasali, Latifeh Karimzadeh, Ingo Laemmermann
Summary: Tissue fibrosis is a common issue in organ aging, caused by the chronic accumulation of senescent cells. Fibroblasts, especially in the skin, play a crucial role in fibrosis by proliferating and depositing excessive extracellular matrix (ECM). This study aims to investigate the influence of senescent fibroblasts and their secretome on dermal fibrosis. The results show that senescent fibroblasts have the potential to be profibrotic, but their secretome failed to induce a fibrotic response in non-senescent cells, contrary to studies on lung fibroblasts.
Article
Chemistry, Applied
Payam Baei, Hamed Daemi, Fatemeh Aramesh, Hossein Baharvand, Mohamadreza Baghaban Eslaminejad
Summary: The purpose of cartilage tissue engineering is to create artificial constructs that mimic native tissue in terms of biological functions and mechanical features, with the aim of improving tissue regeneration. Polysaccharides, due to their structural similarity to the cartilage extracellular matrix (ECM), have attracted attention for developing biomimetic materials. The mechanical properties of constructs and the addition of bioactive molecules play crucial roles in cartilage tissue regeneration. This article discusses polysaccharide-based constructs for cartilage regeneration, with a focus on newly developed biomimetic materials, tuning the mechanical properties of constructs, designing carriers loaded with chondroinductive agents, and the development of appropriate bioinks for bioprinting.
CARBOHYDRATE POLYMERS
(2023)
Review
Biotechnology & Applied Microbiology
Mohammad Soleimani, Kasra Cheraqpour, Raghuram Koganti, Seyed Mahbod Baharnoori, Ali R. Djalilian
Summary: The corneal epithelium consists of nonkeratinized stratified squamous cells, which undergo a significant turnover rate. The limbal epithelial stem cells (LESCs) located in the basal epithelial layer of the limbus play a crucial role in maintaining corneal homeostasis. The limbal stem cell niche (LSCN), composed of various cells, extracellular matrix, and signaling molecules, provides the microenvironment necessary for the proper functioning of LESCs. Damage to the LSCN can lead to limbal stem cell deficiency (LSCD) and conjunctivalization of the cornea. This review summarizes the basics of LSCN and discusses current and emerging bioengineering strategies for LSCN restoration to combat LSCD.
BIOENGINEERING-BASEL
(2023)
Article
Cell Biology
Davood Zaeifi, Mahnaz Azarnia
Summary: The study focuses on efficiently transdifferentiating rat bone marrow-derived mesenchymal stem cells (BM-MSCs) into islet-like cells and encapsulating and transplanting them for the treatment of T1DM. High glucose concentration combined with specific factors is used to induce the transdifferentiation. Encapsulated beta-cells show enhanced viability and functionality, leading to significant reduction of glucose levels in diabetic rats.
CELL AND TISSUE RESEARCH
(2023)
Article
Polymer Science
Effat Nekoueiyfard, Fatemeh Radmanesh, Hossein Baharvand, Athar Mahdieh, Hamid Sadeghi-Abandansari, Rassoul Dinarvand
Summary: The main goal of many researchers is to introduce an intelligent pharmaceutical nanocarrier for targeted drug release and reducing the side effects of chemotherapy. In this study, a reduction-sensitive flower-like magnetomicelle containing doxorubicin (DOX) and magnetic iron oxide nanoparticles (Fe3O4) was synthesized by self-assembly of an amphiphilic triblock copolymer. The innovative design showed high drug loading content, reduced drug release in physiological conditions, fast degradation at the targeted site, and burst release of more drug content at an earlier time. Comparative studies demonstrated that the DOX-loaded magnetomicelle (D-LMM) exhibited superior cellular uptake and toxicity behavior on human breast adenocarcinoma cells compared to non-reduction sensitive control group, free DOX, and a commercial liposomal DOX product.
EUROPEAN POLYMER JOURNAL
(2023)
Article
Medicine, Research & Experimental
Nasim Eslami, Khadijeh Bahrehbar, Fereshteh Esfandiari, Faezeh Shekari, Seyedeh-Nafiseh Hassani, Abdoreza Nazari, Mohammad Pakzad, Hossein Baharvand
Summary: Studies have shown that clonal mesenchymal stem cells (cMSCs) and their derived extracellular vesicles (MSC-EVs) can restore ovarian function in premature ovarian failure (POF). In this study, the therapeutic potential of a homogeneous population of cMSCs and their EV subpopulations was assessed in a mouse model of POF.
Article
Medicine, Research & Experimental
Mahsa Ghorbaninejad, Hamid Asadzadeh-Aghdaei, Hossein Baharvand, Anna Meyfour
Summary: Considering the limitations of 2D cell cultures and tissue models, creating intestinal organoids has become an ideal option for studying the complexity of the intestine. This review discusses the current advances in intestinal organoid development and their applications, particularly in disease modeling and epigenetics. The use of organoids in studying SARSCoV-2 infection and the potential of organoids in evaluating the effects of epigenetic drugs on gastrointestinal diseases are also explored.
Article
Chemistry, Multidisciplinary
Saeed Abbasalizadeh, Sahab Babaee, Reza Kowsari-Esfahan, Zahra Mazidi, Yichao Shi, Jake Wainer, Joaquim M. S. Cabral, Robert Langer, Giovanni Traverso, Hossein Baharvand
Summary: Organoid medicine has made significant progress in the past decade as a novel therapeutic approach for addressing unmet medical needs, such as chronic liver disease. Through the use of scalable and xeno-free differentiation platforms, hepatic progenitors, mesenchymal stromal cells, and endothelial cells are generated from human pluripotent stem cell lines to produce vascularized liver organoids. A scalable microfluidic system is developed to generate cells-loaded microcapsules, which support cell proliferation and the self-organization of liver organoids using a self-biodegradable peptide hydrogel. These vascularized hepatobiliary organoids exhibit key functional features similar to fetal and adult liver tissue, making them promising for liver organoid medicine and drug development.
ADVANCED FUNCTIONAL MATERIALS
(2023)
Article
Neurosciences
Azadeh Amini, Faezeh Shekari, Sara Assar Kashani, Nasim Eslami, Abdoreza Nazari, Nahid Tofigh, Koorosh Shahpasand, Hamid Akbari Javar, Hossein Baharvand
Summary: This study investigated the therapeutic effects of clonal mesenchymal stem cell-derived extracellular vesicles (cMSC-EVs) in traumatic brain injury (TBI) treatment. The results showed that cMSC-EVs efficiently improved cognitive function in TBI animal models, reduced cis p-tau and cleaved caspase3 protein expression, and increased p-PI3K expression. Moreover, cMSC-EVs were able to effectively load an anti-cis p-tau antibody, suggesting their potential use in antibody delivery for passive immunotherapy.
EXPERIMENTAL NEUROLOGY
(2023)
Article
Medicine, Research & Experimental
Sara Assar Kashani, Roghayeh Navabi, Azadeh Amini, Mostafa Hajinasrollah, Yaser Jenab, Shahram Rabbani, Abdoreza Nazari, Mohammad Pakzad, Maedeh Moazenchi, Mohammad Jafari Atrabi, Zakieh Samsonchi, Maryam Hezavehei, Elham Hosseini-Beheshti, Faezeh Shekari, Ensiyeh Hajizadeh-Saffar, Hossein Baharvand
Summary: This study investigated the therapeutic potential of a clonal population of mesenchymal stem cells (cMSC) and their extracellular vesicles (cMSC-EV) subpopulations in vitro and in a type 1 diabetes non-human primate model. The results showed that EV-S110K induced β-cell proliferation and reduced blood glucose levels, inflammatory cytokines, while increasing regulatory T cells and anti-inflammatory cytokines.
Article
Medicine, Research & Experimental
Somayeh Naderi, Zahra Shiri, Masoumeh Zarei-Kheirabadi, Sepideh Mollamohammadi, Parastoo Hosseini, Golnoosh Rahimi, Azadeh Moradmand, Azam Samadian, Amir Shojaei, Meghdad Yeganeh, Seyed Ahmad Mousavi, Motahare Badri, Adeleh Taei, Seyedeh-Nafiseh Hassani, Hossein Baharvand
Summary: This study aimed to generate transplantable midbrain dopaminergic (mDA) progenitors for treatment of Parkinson's Disease (PD). By optimizing the differentiation protocol using clinical-grade human embryonic stem cells (hESC), the researchers successfully obtained functional mDA progenitors. Transplantation of cryopreserved mDA progenitors into rats with 6-hydroxydopamine lesions resulted in functional recovery. This study provides a foundation for future translational applications.
Article
Biochemistry & Molecular Biology
Masumeh Zare, Seyed Ziaeddin Mirhoseini, Shahrokh Ghovvati, Saeed Yakhkeshi, Mahdi Hesaraki, Mojgan Barati, Forough Azam Sayyahpour, Hossein Baharvand, Seyedeh-Nafiseh Hassani
Summary: In many multicellular organisms, mature gametes originate from primordial germ cells (PGCs). Improvements in the culture of PGCs are important not only for developmental biology research, but also for preserving endangered species, and for genome editing and transgenic animal technologies. However, the potential positive impact of SMAD2/3 on the regulation of PGC proliferation has not been taken into consideration.
MOLECULAR REPRODUCTION AND DEVELOPMENT
(2023)
Article
Hematology
Tanmaya Atre, Ali Farrokhi, Sumin Jo, Samuel Salitra, Jesus Duque-Afonso, Michael L. Cleary, Nina Rolf, Gregor S. D. Reid
Summary: Common infections may play a role in the development of pediatric B-cell acute lymphoblastic leukemia (B-ALL), but epidemiologic studies report contradictory effects. Activation of pathogen recognition pathways can generate both proleukemic and antileukemic effects, and the specific outcome depends on the age of the immune system and the binding of Poly(I:C) to endosomal and cytoplasmic receptors.