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Insights into Endothelial Progenitor Cells: Origin, Classification, Potentials, and Prospects.

With the discovery of endothelial progenitor cells (EPCs) in the late 1990s, a paradigm shift in the concept of neoangiogenesis occurred. The identification of circulating EPCs in peripheral blood marked the beginning of a new era with enormous potential in the rapidly transforming regenerative field. Overwhelmed with the revelation, researchers across the globe focused on isolating, defining, and interpreting the role of EPCs in various physiological and pathological conditions. Consequently, controversies emerged regarding the isolation techniques and classification of EPCs. Nevertheless, th

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… The SCL gene specifies haemangioblast development from early mesoderm. The EMBO Journal. 1998;17(14):4029–4045. doi: 10.1093/emboj/17.14.4029. 44. Gering M., Yamada Y., Rabbitts T. H., Patient R. K. … Lmo2 and Scl/Tal1 convert non-axial mesoderm into haemangioblasts which differentiate into endothelial cells in the absence of Gata1. Development. 2003;130(25):6187–6199. doi: 10.1242/dev.00875. 45. Patterson L. J., Gering M., Eckfeldt C. E., et al. …

Роль оси CXCL12/CXCR4/CXCR7 в когнитивном повреждении, связанном с нейродегенеративными заболеваниями.

Нейродегенеративные заболевания, включая болезнь Альцгеймера (AD), болезнь Паркинсона (PD), множественный склероз (MS) и амиотропический боковой склероз (ALS), характеризуются постепенной нейронной потерей и когнитивным расстройством (CI). Ось Cystine-X-cystine chemokine ligand 12 (CXCL12)/CXC chemokine рецептор типа 4 (CXCR4)/CXC chemokine рецептор типа 7 (CXCR7) стала критическим молекулярным путем развития CI в этих расстройствах. В настоящем обзоре изучается роль этой оси в патогенезе интеллигенции в связи с этими нейродегенеративными заболеваниями, синтезируются имеющиеся данные и ее посл

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… This cytokine can be secreted from various sites originating from different embryonic layers, such as astrocytes arising from ectoderm and CD4 + T-cells arising from mesoderm ( Luo et al., 2016a ; de Bock and Cools, 2015 ). … Embryologically, CXCR4 is derived from the mesoderm and endoderm layers( Terheyden-Keighley et al., 2022 ) . In the CNS, CXCR4 is expressed in glial cells, particularly astrocytes, and some neurons called neuronal progenitor cells (NPC). These cells can release CXCR4 in response to inflammation. …

Molecular mechanisms in calvarial bone and suture development, and their relation to craniosynostosis.

The development and growth of the skull is a co-ordinated process involving many different tissues that interact with each other to form a complex end result. When normal development is disrupted, debilitating pathological conditions, such as craniosynostosis (premature calvarial suture fusion) and cleidocranial dysplasia (delayed suture closure), can result. It is known that mutations in the fibroblast growth factor receptors 1, 2, and 3(FGFR1, 2, and 3), as well as the transcription factors MSX2 and TWIST cause craniosynostosis, and that mutations in the transcription factor RUNX2 (CBFA1) ca

Vascular abnormalities and deregulation of VEGF in Lkb1-deficient mice.

The LKB1 tumor suppressor gene, mutated in Peutz-Jeghers syndrome, encodes a serine/threonine kinase of unknown function. Here we show that mice with a targeted disruption of Lkb1 die at midgestation, with the embryos showing neural tube defects, mesenchymal cell death, and vascular abnormalities. Extraembryonic development was also severely affected; the mutant placentas exhibited defective labyrinth layer development and the fetal vessels failed to invade the placenta. These phenotypes were associated with tissue-specific deregulation of vascular endothelial growth factor (VEGF) expression,

Activation of the pro-survival phosphatidylinositol 3-kinase/AKT pathway by transforming growth factor-beta1 in mesenchymal cells is mediated by p38 MAPK-dependent induction of an autocrine growth factor.

Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine involved in differentiation, growth, and survival of mesenchymal cells while inhibiting growth/survival of most other cell types. The mechanism(s) of pro-survival signaling by TGF-beta1 in mesenchymal cells is unclear. In this report, we demonstrate that TGF-beta1 protects against serum deprivation-induced apoptosis of mesenchymal cells isolated from patients with acute lung injury and of normal human fetal lung fibroblasts (IMR-90). TGF-beta receptor(s)-activated signaling in these cells involves rapid activation of th

Advances in the mechanism and therapies of achondroplasia.

Achondroplasia (ACH), is the prevailing type of genetic dwarfism in humans, caused by mutations in fibroblast growth factor receptor 3 (FGFR3) that are inherited in an autosomal dominant manner. FGFR3 is mainly expressed in condensed mesenchyme, chondrocytes, and mature osteoblasts and osteoclasts, in which it regulates the formation, development, growth, and remodeling of the skeletal system. Mutations in FGFR3 causing ACH result in enhanced FGFR3 signaling through combined mechanisms including enhancing FGF dimerization and tyrosine kinase activity and stabilizing FGF receptors. In ACH, supp

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… Mesodermal cells originating from the prechordal region give rise to cartilage and bone tissue, forming the posterior part of the skull. … The paraxial mesoderm (somites) forms the axial skeleton, while the appendicular skeleton originates from the lateral plate mesodermal cells. 12 Skeleton formation initiates when mesenchymal cells originating from the aforementioned embryonic lineages migrate to the locations where the bones will form …

Двойная роль микроглии в множественном склерозе и его последствия для диагностики и ремонта.

Микроглия играет ключевую роль в развитии, иммунной слежке и восстановлении центральной нервной системы. Эти клетки играют многогранную роль в множестве склероза (MS), при этом есть основания полагать, что микроглия может способствовать как активному воспалению, так и воспалению. Например, было продемонстрировано, что микроглия может поддерживать разработку олигодендроцитов и фигоцитоза миелиновых обломков, способствуя тем самым надлежащему восстановлению. Однако чрезмерная активация микроглии в повреждениях MS усугубляет нейроинфламму, высвобождая подстрекательские цитокины и облегчая активац

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… INTRODUCTION Microglia Origin and Functions in the Healthy and Diseased Brain Microglia are mesodermal cells derived from the yolk sac, differing from other glial cells, as oligodendrocytes and astrocytes, which originate from the neuroectoderm [ 1 ]. … Initially thought to derive from macrophages and tissue monocytes, it is now established that microglia originate from mesodermal progenitor cells that colonize the central nervous system (CNS) early during embryogenesis. …

Stem Cells and Organ Transplantation: Resetting Our Biological Clocks

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… More technically, ESCs can produce cells arising from any of the three “germ” layers in our bodies—the endoderm, mesoderm, and ectoderm . … Mesenchymal stem cells are derived from the mesoderm germ line . …

CARMN оркестрирует ангиогенез из-за оперных сцен: подписывает любовные письма в эндотелий.

Одной из основных причин заболеваемости и потери конечностей по-прежнему является хроническая ишемия, угрожающая конечностям (CLTI), стадия заболевания периферической артерией (PAD). Эффективные стратегии сосудистой регенерации потребуют более глубокого понимания молекулярных механизмов, лежащих в основе ангиогенеза. Последние данные свидетельствуют о новой роли сосудистого гладкого мышечного клеточного (VSMC-обогащенного) длинного некодирующего RNA (lncRNA) CARMN в эндотелиальном ангиогенезе и послеишерном сосудистом ремонте. CARMN был понижен как в мышечной ткани человека CLTI, так и в модел

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… Their study advances this field by identifying a paracrine signaling mechanism wherein a smooth muscle cell–enriched long noncoding RNA (lncRNA), CARMN (cardiac mesoderm enhancer-associated noncoding RNA) ( 7 , 8 ), regulates endothelial angiogenic activity through a miRNA-mediated Hedgehog signaling …

Concise Review: Regulation of Self-Renewal in Normal and Malignant Hematopoietic Stem Cells by Krüppel-Like Factor 4.

Pluripotent and tissue-specific stem cells, such as blood-forming stem cells, are maintained through a balance of quiescence, self-renewal, and differentiation. Self-renewal is a specialized cell division that generates daughter cells with the same features as the parental stem cell. Although many factors are involved in the regulation of self-renewal, perhaps the most well-known factors are members of the Krüppel-like factor (KLF) family, especially KLF4, because of the landmark discovery that this protein is required to reprogram somatic cells into induced pluripotent stem cells. Because KLF

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… Based on chromatin immunoprecipitation and sequencing analysis, KLF4 and KLF5 inhibit differentiation of mesoderm and endoderm in ESCs by activating targets other than NANOG 18 . … Klf4 and Klf5 differentially inhibit mesoderm and endoderm differentiation in embryonic stem cells . Nat Commun 2014 ; 5 : 3719 . 24770696 10.1038/ncomms4719 19 Yu F , Li J , Chen H et al. …

Clinical Trials of Stem Cell Therapy in Japan: The Decade of Progress under the National Program.

Stem cell therapy is a current world-wide topic in medical science. Various therapies have been approved based on their effectiveness and put into practical use. In Japan, research and development-related stem cell therapy, generally referred to as regenerative medicine, has been led by the government. The national scheme started in 2002, and support for the transition to clinical trials has been accelerating since 2011. Of the initial 18 projects that were accepted in the budget for preclinical research, 15 projects have begun clinical trials so far. These include the transplantation of retin

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… Single cell transcriptomics identifies a signaling network coordinating endoderm and mesoderm diversification during foregut organogenesis Nat. Commun. 2020 11 4158 10.1038/s41467-020-17968-x 32855417 PMC7453027 66. Kishimoto K. Furukawa K.T. Luz-Madrigal A. Yamaoka A. Matsuoka C. Habu M. Alev C. … Bidirectional Wnt signaling between endoderm and mesoderm confers tracheal identity in mouse and human cells Nat. Commun. 2020 11 4159 10.1038/s41467-020-17969-w 32855415 PMC7453000 67. Tamura R. Miyoshi H. Imaizumi K. Yo M. Kase Y. Sato T. Sato M. Morimoto Y. Sampetrean O. Kohyama J. …

Mesenchymal Stem Cell Therapy for Neurological Complications of Prematurity: A Narrative Review.

Background: Preterm birth is a leading cause of neonatal mortality and long-term disability worldwide. Injury in premature infants is demonstrated by disrupted organ development from inflammation, oxidative stress, hypoxia, and impaired vascular maturation. Current therapies largely provide supportive care and do not directly promote tissue regeneration. Mesenchymal stem cell (MSC)-based therapies have emerged as a potential strategy to enhance endogenous repair across organ systems commonly affected by prematurity. Results: Evidence indicates that MSCs exert therapeutic effects primarily thro

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… MSCs are multipotent cells derived from mesodermal tissues [ 10 ]. Common sources include bone marrow, adipose tissue, skeletal muscle, peripheral blood, umbilical cord, placenta, fetal tissue, and amniotic fluid [ 13 ]. … Stem cells have shown promise across multiple tissue types, including mesoderm-derived tissues (bone, cartilage, muscle), nervous tissue, skin, and organs such as the liver, gastrointestinal tract, vasculature, and lungs [ 10 ]. …

Skeletal Site-specific Effects of Zoledronate on in vivo Bone Remodeling and in vitro BMSCs Osteogenic Activity.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) has been associated with long-term oral or intravenous administration of nitrogen-containing bisphosphonates (BPs). However, the pathogenesis of BRONJ remains unknown, and definitively effective treatment has not yet been established. Bisphosphonate-related osteonecrosis (BRON) tends to occur in maxillofacial bones. Why this occurs is still unclear. Here we show that zoledronate (Zol) treatment suppresses alveolar bone remodeling after tooth typical clinical and radiographic hallmarks of the human BRONJ, whereas enhances peripheral bone q

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… Developmentally, maxillofacial bones originate exclusively from neuroectoderm and are formed primarily by intramembranous ossification 24 25 , whereas peripheral bones develop from mesoderm and undergo both endochondral and intramembranous ossification 26 . … Developmentally, jaw bones originate exclusively from neuroectoderm and undergo primarily intramembranous ossification, whereas peripheral bones develop from mesoderm and are formed by both endochondral and intramembranous ossification 24 25 26 . …

Polymorphic Variants of Genes Encoding Angiogenesis-Related Factors in Infertile Women with Recurrent Implantation Failure.

Recurrent implantation failure (RIF) is a global health issue affecting a significant number of infertile women who undergo in vitro fertilization (IVF) cycles. Extensive vasculogenesis and angiogenesis occur in both maternal and fetal placental tissues, and vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) family molecules and their receptors are potent angiogenic mediators in the placenta. Five single nucleotide polymorphisms (SNPs) in the genes encoding angiogenesis-related factors were selected and genotyped in 247 women who had undergone the ART procedure and 12

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… In the next phase, the embryo invades the endometrium and blood cells arise from the mesoderm. A normal pregnancy requires the development of the complex vascular network of both the mother and the fetus to meet the increasing oxygen and metabolic demands of the developing embryo. … The embryonic vasculature is formed by the segregation, migration and assembly of mesodermal angioblasts, a process called vasculogenesis. In the complex process of angiogenesis, the activity of many growth factors and their receptors on various pathways plays a key role. …

Human-Induced Pluripotent Stem Cell Models for Amyloid Cardiomyopathy: From Mechanistic Insights to Therapeutic Discovery.

Amyloid cardiomyopathy (ACM), driven by transthyretin (TTR) and immunoglobulin light chain (LC) amyloid fibrils, remains a major clinical challenge due to limited mechanistic understanding and insufficient preclinical models. Human-induced pluripotent stem cells (iPSCs) have emerged as a transformative platform to model ACM, offering patient-specific and genetically controlled systems. In this review, we summarize recent advances in the use of iPSC-derived cardiomyocytes (iPSC-CMs) in both two-dimensional (2D) monolayer cultures and three-dimensional (3D) constructs-including spheroids, organo

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… These signals emulate the hepatic-inductive cues secreted by the cardiogenic mesoderm in embryonic development, driving the expression of hepatic progenitor markers like alpha-fetoprotein (AFP) and hepatocyte nuclear factor 4 alpha (HNF4α); and (3) The final maturation step utilizes hepatocyte growth … The temporal control of these pathways enables a stage-wise transition from mesoderm induction (Wnt signaling activation) to cardiac progenitor specification (Wnt signaling inhibition) and maturation, with differentiation efficiency reaching up to 95% cardiac troponin T type 2 (TNNT2) positive cells …

Prediction of cancer drugs by chemical-chemical interactions.

Cancer, which is a leading cause of death worldwide, places a big burden on health-care system. In this study, an order-prediction model was built to predict a series of cancer drug indications based on chemical-chemical interactions. According to the confidence scores of their interactions, the order from the most likely cancer to the least one was obtained for each query drug. The 1(st) order prediction accuracy of the training dataset was 55.93%, evaluated by Jackknife test, while it was 55.56% and 59.09% on a validation test dataset and an independent test dataset, respectively. The propos

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… Moreover, the regimen including cisplatin, adriamycin, and dacarbazine was reported to be effective for patients with metastatic uterine and ovarian mixed mesodermal sarcomas [82] . … Baker TR, Piver MS, Caglar H, Piedmonte M (1991) Prospective trial of cisplatin, adriamycin, and dacarbazine in metastatic mixed mesodermal sarcomas of the uterus and ovary. Am J Clin Oncol 14: 246–250. 83. http://www.drugbank.ca/drugs/DB01268 . (accessed March 31, 2013). 84. …

Osteoimmunopathology in HIV/AIDS: A Translational Evidence-Based Perspective.

Infection with the human immunodeficiency virus-1 (HIV) and the resulting acquired immune deficiency syndrome (AIDS) alter not only cellular immune regulation but also the bone metabolism. Since cellular immunity and bone metabolism are intimately intertwined in the osteoimmune network, it is to be expected that bone metabolism is also affected in patients with HIV/AIDS. The concerted evidence points convincingly toward impaired activity of osteoblasts and increased activity of osteoclasts in patients with HIV/AIDS, leading to a significant increase in the prevalence of osteoporosis. Research

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… The mesenchyme is a type of loose connective tissue, derived from the three embryonic germ layers (i.e., endoderm, mesoderm, and ectoderm). In ontogenic development, the mesodermal middle layer gives rise to the skeleton and the hematopoietic system [ 32 ]. …

A Rare Case of Systemic Amyloidosis Involving the Thyroid in a Young Patient.

Thyroid amyloidosis is a rare condition associated with thyroid pathologies such as medullary carcinoma, papillary carcinoma, amyloid goitre, and benign lesions, with a clinically palpable goitre being exceptionally uncommon. As a result, many cases of benign thyroid enlargement caused by amyloid deposits remain undiagnosed. A 28-year-old male patient noticed progressive neck circumference enlargement, voice alteration, decreased appetite, weight loss, dysphagia, fever, and night sweats. Fine-needle aspiration biopsy of the thyroid gland did not reveal the cause of the goitre. A total thyroide

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… Primary amyloidosis limited to tissue of mesodermal origin Am. J. Pathol. 1935 11 977 988 19970245 PMC1910997 17. Leszczyńska M. Borucki Ł. Popko M. Amyloidoza w obrębie głowy i szyi Otolaryngol. Pol. 2008 62 643 648 10.1016/S0030-6657(08)70333-0 19004276 18. Cannizzaro M.A. Lo Bianco S. …

Методологии изучения мозговых органоидов для изучения механизмов заболевания в прогрессивном множественном склерозе.

Множественный склероз (MS) — изнуряющее аутоиммунное расстройство, направленное против центральной нервной системы (CNS), отмечен непрерывным обезвоживанием и воспалением. В клинической форме она представляет в трех различных формах: повторные выбросы MS (RRMS), первичные прогрессивные MS (PPMS) и вторичные прогрессивные MS (SPMS). Несмотря на то, что лечение с целью изменения болезней (ДМР) оказывает определенное содействие людям, страдающим СВЗ, варианты лечения прогрессивных СЗМ (ПМС) по-прежнему являются крайне неадекватными. Этот пробел свидетельствует о настоятельной необходимости примен

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… Brain organoids predominantly comprise cells originating from the neuroectodermal lineage, constraining non-neuronal differentiation such as the mesodermal-derived microglia and vascular cells. … Microglia originate from the yolk sac and migrate to the mesoderm during development, differing from neural and glial cells that arise from the neuroectodermal lineage. …

Последние достижения в области мезенхимической стволовой клеточной терапии для множественных склерозов: клинические виды применения и проблемы.

Множественный склероз (MS), хроническое аутоиммунное расстройство центральной нервной системы (CNS), характеризуется воспалением, обезвоживанием и нейродегенерацией, что приводит к различным клиническим проявлениям, таким, как усталость, сенсорное расстройство и когнитивная дисфункция. Текущее фармакологическое лечение направлено прежде всего на иммунную модуляцию, но не позволяет остановить прогрессию заболеваний или полностью обратить на нет повреждения CNS. Лечение стволовыми клетками (MSC) является многообещающей альтернативой, используя иммуномудуляторы, нейрозащиту и регенеративные спосо

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… Various non-mesodermal cell lineages have been observed to undergo differentiation, including alveolar cells, hepatocytes, epithelial cells, astrocytes, mature neurons, and neural precursors. … Differentiate into mesodermal lineage cells ( Uccelli et al., 2011 ) -Painful and invasive extraction methods with limited efficiency ( Quirici et al., 2002 ) -Release BDNF and promote ODC generation -Ineffectiveness in managing stabilized MS progression ( Darlington et al., 2011 ) -Show immunomodulatory …