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Cell Transplantation 2024Multipotent mesenchymal stem cells (MSCs) have high self-renewal and multi-lineage differentiation potentials and low immunogenicity, so they have attracted much... (Review)
Review
Multipotent mesenchymal stem cells (MSCs) have high self-renewal and multi-lineage differentiation potentials and low immunogenicity, so they have attracted much attention in the field of regenerative medicine and have a promising clinical application. MSCs originate from the mesoderm and can differentiate not only into osteoblasts, cartilage, adipocytes, and muscle cells but also into ectodermal and endodermal cell lineages across embryonic layers. To design cell therapy for replacement of damaged tissues, it is essential to understand the signaling pathways, which have a major impact on MSC differentiation, as this will help to integrate the signaling inputs to initiate a specific lineage. Hedgehog (Hh) signaling plays a vital role in the development of various tissues and organs in the embryo. As a morphogen, Hh not only regulates the survival and proliferation of tissue progenitor and stem populations but also is a critical moderator of MSC differentiation, involving tri-lineage and across embryonic layer differentiation of MSCs. This review summarizes the role of Hh signaling pathway in the differentiation of MSCs to mesodermal, endodermal, and ectodermal cells.
Topics: Mesenchymal Stem Cells; Hedgehog Proteins; Humans; Cell Differentiation; Signal Transduction; Animals; Multipotent Stem Cells
PubMed: 38695366
DOI: 10.1177/09636897241244943 -
Frontiers in Molecular Biosciences 2024Craniofacial reconstruction faces many challenges, including high complexity, strong specificity, severe injury, irregular and complex wounds, and high risk of bleeding.... (Review)
Review
Craniofacial reconstruction faces many challenges, including high complexity, strong specificity, severe injury, irregular and complex wounds, and high risk of bleeding. Traditionally, the "gold standard" for treating craniofacial bone defects has been tissue transplantation, which involves the transplantation of bone, cartilage, skin, and other tissues from other parts of the body. However, the shape of craniofacial bone and cartilage structures varies greatly and is distinctly different from ordinary long bones. Craniofacial bones originate from the neural crest, while long bones originate from the mesoderm. These factors contribute to the poor effectiveness of tissue transplantation in repairing craniofacial defects. Autologous mesenchymal stem cell transplantation exhibits excellent pluripotency, low immunogenicity, and minimally invasive properties, and is considered a potential alternative to tissue transplantation for treating craniofacial defects. Researchers have found that both craniofacial-specific mesenchymal stem cells and mesenchymal stem cells from other parts of the body have significant effects on the restoration and reconstruction of craniofacial bones, cartilage, wounds, and adipose tissue. In addition, the continuous development and application of tissue engineering technology provide new ideas for craniofacial repair. With the continuous exploration of mesenchymal stem cells by researchers and the continuous development of tissue engineering technology, the use of autologous mesenchymal stem cell transplantation for craniofacial reconstruction has gradually been accepted and promoted. This article will review the applications of various types of mesenchymal stem cells and related tissue engineering in craniofacial repair and reconstruction.
PubMed: 38690295
DOI: 10.3389/fmolb.2024.1362338 -
Acta Medica Okayama Apr 2024Soft-tissue sarcoma (STS) is a heterogeneous group of rare tumors originating predominantly from the embryonic mesoderm. Despite the development of combined modalities...
Soft-tissue sarcoma (STS) is a heterogeneous group of rare tumors originating predominantly from the embryonic mesoderm. Despite the development of combined modalities including radiotherapy, STSs are often refractory to antitumor modalities, and novel strategies that improve the prognosis of STS patients are needed. We previously demonstrated the therapeutic potential of two telomerase-specific replication-competent oncolytic adenoviruses, OBP-301 and tumor suppressor p53-armed OBP-702, in human STS cells. Here, we demonstrate in vitro and in vivo antitumor effects of OBP-702 in combination with ionizing radiation against human STS cells (HT1080, NMS-2, SYO-1). OBP-702 synergistically promoted the antitumor effect of ionizing radiation in the STS cells by suppressing the expression of B-cell lymphoma-X large (BCL-xL) and enhancing ionizing radiation-induced apoptosis. The in vivo experiments demonstrated that this combination therapy significantly suppressed STS tumors' growth. Our results suggest that OBP-702 is a promising antitumor reagent for promoting the radiosensitivity of STS tumors.
Topics: Sarcoma; Humans; Oncolytic Virotherapy; bcl-X Protein; Radiation Tolerance; Cell Line, Tumor; Animals; Tumor Suppressor Protein p53; Mice; Apoptosis; Adenoviridae
PubMed: 38688833
DOI: 10.18926/AMO/66924 -
PLoS Biology Apr 2024As tissues grow and change shape during animal development, they physically pull and push on each other, and these mechanical interactions can be important for...
As tissues grow and change shape during animal development, they physically pull and push on each other, and these mechanical interactions can be important for morphogenesis. During Drosophila gastrulation, mesoderm invagination temporally overlaps with the convergence and extension of the ectodermal germband; the latter is caused primarily by Myosin II-driven polarised cell intercalation. Here, we investigate the impact of mesoderm invagination on ectoderm extension, examining possible mechanical and mechanotransductive effects on Myosin II recruitment and polarised cell intercalation. We find that the germband ectoderm is deformed by the mesoderm pulling in the orthogonal direction to germband extension (GBE), showing mechanical coupling between these tissues. However, we do not find a significant change in Myosin II planar polarisation in response to mesoderm invagination, nor in the rate of junction shrinkage leading to neighbour exchange events. We conclude that the main cellular mechanism of axis extension, polarised cell intercalation, is robust to the mesoderm invagination pull. We find, however, that mesoderm invagination slows down the rate of anterior-posterior cell elongation that contributes to axis extension, counteracting the tension from the endoderm invagination, which pulls along the direction of GBE.
PubMed: 38683880
DOI: 10.1371/journal.pbio.3002611 -
PLoS Biology Apr 2024Brain pericytes are one of the critical cell types that regulate endothelial barrier function and activity, thus ensuring adequate blood flow to the brain. The genetic...
Brain pericytes are one of the critical cell types that regulate endothelial barrier function and activity, thus ensuring adequate blood flow to the brain. The genetic pathways guiding undifferentiated cells into mature pericytes are not well understood. We show here that pericyte precursor populations from both neural crest and head mesoderm of zebrafish express the transcription factor nkx3.1 develop into brain pericytes. We identify the gene signature of these precursors and show that an nkx3.1-, foxf2a-, and cxcl12b-expressing pericyte precursor population is present around the basilar artery prior to artery formation and pericyte recruitment. The precursors later spread throughout the brain and differentiate to express canonical pericyte markers. Cxcl12b-Cxcr4 signaling is required for pericyte attachment and differentiation. Further, both nkx3.1 and cxcl12b are necessary and sufficient in regulating pericyte number as loss inhibits and gain increases pericyte number. Through genetic experiments, we have defined a precursor population for brain pericytes and identified genes critical for their differentiation.
PubMed: 38683849
DOI: 10.1371/journal.pbio.3002590 -
Frontiers in Bioscience (Landmark... Apr 2024Pericytes, a specific type of mesenchymal cell that surround the basement membrane of pulmonary venules and capillaries. They are crucial pathological features observed... (Review)
Review
Pericytes, a specific type of mesenchymal cell that surround the basement membrane of pulmonary venules and capillaries. They are crucial pathological features observed in individuals with the severe lung disease of pulmonary fibrosis (PF). The presence of pericytes leads to inflammation and fibrosis in the lung interstitium and alveolar space due to the release of various cytokines and chemokines. Pericytes also stimulate the proliferation and activation of fibroblasts, thereby promoting the progression of PF. Previous studies examining the mechanism of action of pericytes have primarily focused on cell signal transduction pathways, cell growth and death processes, and the synthesis and breakdown of extracellular matrix (ECM). Notably, the transforming growth factor-β (TGF-β) and Wnt signaling pathways have been associated with the action of pericytes in driving the progression of PF. It is therefore clear that pericytes play an essential role in the development of PF, while also offering possible avenues for targeted therapeutic intervention against this condition. The current article provides a comprehensive review on how pericytes contribute to inflammatory responses, as well as their importance for understanding the mechanism of PF. In addition, this review discusses the potential use of pericyte-targeted approaches for the treatment of patients affected by this debilitating lung disease.
Topics: Pericytes; Humans; Pulmonary Fibrosis; Animals; Transforming Growth Factor beta; Signal Transduction; Extracellular Matrix; Wnt Signaling Pathway
PubMed: 38682199
DOI: 10.31083/j.fbl2904141 -
Frontiers in Bioscience (Landmark... Apr 2024Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder characterized by aberrant amyloid precursor protein (APP) cleavage, pathological... (Review)
Review
Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder characterized by aberrant amyloid precursor protein (APP) cleavage, pathological aggregations of beta-amyloid (Aβ) that make up Aβ plaques and hyperphosphorylation of Tau that makes up neurofibrillary tangles (NFTs). Although progress has been made in research on AD, the fundamental causes of this disease have not been fully elucidated. Recent studies have shown that vascular dysfunction especially the loss of pericytes plays a significant role in the onset of AD. Pericytes play a variety of important roles in the nervous system including the regulation of the cerebral blood flow (CBF), the formation and maintenance of the blood-brain barrier (BBB), angiogenesis, and the clearance of toxic substances from the brain. Pericytes participate in the transport of Aβ through various receptors, and Aβ acts on pericytes to cause them to constrict, detach, and die. The loss of pericytes elevates the levels of Aβ1-40 and Aβ1-42 by disrupting the integrity of the BBB and reducing the clearance of soluble Aβ from the brain interstitial fluid. The aggravated deposition of Aβ further exacerbates pericyte dysfunction, forming a vicious cycle. The combined influence of these factors eventually results in the loss of neurons and cognitive decline. Further exploration of the interactions between pericytes and Aβ is beneficial for understanding AD and could lead to the identification of new therapeutic targets for the prevention and treatment of AD. In this review, we explore the characterization of pericytes, interactions between pericytes and other cells in the neurovascular unit (NVU), and the physiological functions of pericytes and dysfunctions in AD. This review discusses the interactions between pericytes and Aβ, as well as current and further strategies for preventing or treating AD targeting pericytes.
Topics: Pericytes; Alzheimer Disease; Humans; Amyloid beta-Peptides; Blood-Brain Barrier; Animals; Brain
PubMed: 38682184
DOI: 10.31083/j.fbl2904136 -
Stem Cell Research Apr 2024GATA6 is expressed during early embryogenesis and localizes to endoderm- and mesoderm-derived tissues during later embryogenesis. Here, we established a human induced...
GATA6 is expressed during early embryogenesis and localizes to endoderm- and mesoderm-derived tissues during later embryogenesis. Here, we established a human induced pluripotent stem cell (hiPSC) line expressing EGFP under GATA6 gene. EGFP coding sequence was introduced into the C-terminus of GATA6 in KSCBi017-A hiPSCs through homologous recombination using CRISPR/Cas9 system. The successfully edited line, KSCBi017-A-1, was selected and confirmed by sequencing. The line had a normal karyotype and exhibited potential to differentiate into three germ layers while it expressed EGFP upon endoderm induction. KSCBi017-A-1 cells can be used to monitor the expression of GATA6 during differentiation. This cell line is available from Korea National Stem Cell Bank.
PubMed: 38678980
DOI: 10.1016/j.scr.2024.103426 -
International Journal of Molecular... Apr 2024This review deals with the developmental origins of extraocular, jaw and laryngeal muscles, the expression, regulation and functional significance of sarcomeric myosin... (Review)
Review
This review deals with the developmental origins of extraocular, jaw and laryngeal muscles, the expression, regulation and functional significance of sarcomeric myosin heavy chains (MyHCs) that they express and changes in MyHC expression during phylogeny. Myogenic progenitors from the mesoderm in the prechordal plate and branchial arches specify craniofacial muscle allotypes with different repertoires for MyHC expression. To cope with very complex eye movements, extraocular muscles (EOMs) express 11 MyHCs, ranging from the superfast extraocular MyHC to the slowest, non-muscle MyHC IIB (nmMyH IIB). They have distinct global and orbital layers, singly- and multiply-innervated fibres, longitudinal MyHC variations, and palisade endings that mediate axon reflexes. Jaw-closing muscles express the high-force masticatory MyHC and cardiac or limb MyHCs depending on the appropriateness for the acquisition and mastication of food. Laryngeal muscles express extraocular and limb muscle MyHCs but shift toward expressing slower MyHCs in large animals. During postnatal development, MyHC expression of craniofacial muscles is subject to neural and hormonal modulation. The primary and secondary myotubes of developing EOMs are postulated to induce, via different retrogradely transported neurotrophins, the rich diversity of neural impulse patterns that regulate the specific MyHCs that they express. Thyroid hormone shifts MyHC 2A toward 2B in jaw muscles, laryngeal muscles and possibly extraocular muscles. This review highlights the fact that the pattern of myosin expression in mammalian craniofacial muscles is principally influenced by the complex interplay of cell lineages, neural impulse patterns, thyroid and other hormones, functional demands and body mass. In these respects, craniofacial muscles are similar to limb muscles, but they differ radically in the types of cell lineage and the nature of their functional demands.
Topics: Animals; Humans; Myosin Heavy Chains; Phylogeny; Gene Expression Regulation, Developmental; Muscle Development; Facial Muscles; Oculomotor Muscles
PubMed: 38674131
DOI: 10.3390/ijms25084546 -
International Journal of Oral Science Apr 2024Precise orchestration of cell fate determination underlies the success of scaffold-based skeletal regeneration. Despite extensive studies on mineralized parenchymal...
Precise orchestration of cell fate determination underlies the success of scaffold-based skeletal regeneration. Despite extensive studies on mineralized parenchymal tissue rebuilding, regenerating and maintaining undifferentiated mesenchyme within calvarial bone remain very challenging with limited advances yet. Current knowledge has evidenced the indispensability of rebuilding suture mesenchymal stem cell niches to avoid severe brain or even systematic damage. But to date, the absence of promising therapeutic biomaterials/scaffolds remains. The reason lies in the shortage of fundamental knowledge and methodological evidence to understand the cellular fate regulations of scaffolds. To address these issues, in this study, we systematically investigated the cellular fate determinations and transcriptomic mechanisms by distinct types of commonly used calvarial scaffolds. Our data elucidated the natural processes without scaffold transplantation and demonstrated how different scaffolds altered in vivo cellular responses. A feasible scaffold, polylactic acid electrospinning membrane (PLA), was next identified to precisely control mesenchymal ingrowth and self-renewal to rebuild non-osteogenic suture-like tissue at the defect center, meanwhile supporting proper osteointegration with defect bony edges. Especially, transcriptome analysis and cellular mechanisms underlying the well-orchestrated cell fate determination of PLA were deciphered. This study for the first time cellularly decoded the fate regulations of scaffolds in suture-bony composite defect healing, offering clinicians potential choices for regenerating such complicated injuries.
Topics: Tissue Scaffolds; Animals; Transcriptome; Bone Regeneration; Polyesters; Skull; Mesenchymal Stem Cells; Mesoderm; Cell Differentiation; Tissue Engineering; Cranial Sutures; Biocompatible Materials
PubMed: 38654018
DOI: 10.1038/s41368-024-00295-y