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Mesenchymal Stromal Cell Therapy in Solid Organ Transplantation.

Transplantation is the gold-standard treatment for the failure of several solid organs, including the kidneys, liver, heart, lung and small bowel. The use of tailored immunosuppressive agents has improved graft and patient survival remarkably in early post-transplant stages, but long-term outcomes are frequently unsatisfactory due to the development of chronic graft rejection, which ultimately leads to transplant failure. Moreover, prolonged immunosuppression entails severe side effects that severely impact patient survival and quality of life. The achievement of tolerance, i.e., stable graft

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… More recent evidence suggests that MSC reside in the vascular niches, being either identical to or deriving from pericytes ( 20 ). Here, MSC stabilize the vascular network, contribute to the normal tissues and immune homeostasis, and modulate osteoclast formation. …

Targeting cytokine and chemokine signaling pathways for cancer therapy.

Cytokines are critical in regulating immune responses and cellular behavior, playing dual roles in both normal physiology and the pathology of diseases such as cancer. These molecules, including interleukins, interferons, tumor necrosis factors, chemokines, and growth factors like TGF-β, VEGF, and EGF, can promote or inhibit tumor growth, influence the tumor microenvironment, and impact the efficacy of cancer treatments. Recent advances in targeting these pathways have shown promising therapeutic potential, offering new strategies to modulate the immune system, inhibit tumor progression, and o

Biology of stem cell paradox: a double-edged sword-implications for cancer therapy.

This comprehensive review investigates the complex interactions between oncogenesis and stem cells, underscoring the crucial importance of cancer stem cells (CSCs) in the mechanisms of tumorigenesis, metastatic dissemination, and resistance to therapeutic interventions. CSCs constitute a distinct subset within neoplasms, defined by unique characteristics such as the ability to self-renew, the potential to differentiate into various cellular phenotypes, and an inherent resistance to conventional treatment strategies. It is hypothesized that these properties are regulated by a multitude of signa

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… CAFs can originate from quiescent stellate cells, tissue-resident fibroblasts, mesenchymal stem cells (MSCs), endothelial cells, pericytes, or other cell types. …

Nanogel-Based Precision Bone Regeneration: Rational Design, Biological Barrier Penetration, and Osteoporotic Microenvironment Remodeling.

The pathogenesis of osteoporosis is primarily associated with impaired communication between osteoblasts and osteoclasts, leading to disrupted bone homeostasis. Conventional biomaterials mainly rely on macroscopic structural support and are limited in their ability to precisely regulate the complex bone microenvironment and overcome biological barriers. As representative soft matter nanoplatforms, nanogels possess unique viscoelastic mechanical properties and adaptive biointerfacial properties, offering new opportunities to overcome physical barriers within bone tissues. Moving beyond previous

Кардиотоксичность, вызванная множественными миэломатерапиями: механистическая конвергенция между протеиновыми ингибиторами, CAR-T и биконкретными антителами.

Сердечно-сосудистая токсичность стала важным препятствием на пути реализации полного клинического потенциала современной терапии для множественных миэломы (ММ), включая протеазонные ингибиторы (ИП), химерика антигенного рецептора Т-клеток (CAR-T) и CD3-engaging Биотипные антитела. Здесь мы обсуждаем эпидемиологию, лежащую в основе механистических путей, и новые стратегии предотвращения кардиотоксичности, вызванной терапией, в MM. На основе данных, полученных в ходе исследований по изучению мультиомики, доклинических моделей и данных наблюдений в реальном мире, мы синтезируем вклад митохондриал

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… TNF-α-sensitive brain pericytes activate microglia by releasing IL-6 through cooperation between IκB-NFκB and JAK-STAT3 pathways. Brain Res. 2018;1692:34–44. 10.1016/j.brainres.2018.04.023. 138. Xue YL, Zhang SX, Zheng CF, Li YF, Zhang LH, Hao YF, et al. …

Breaking the Resistance: Photodynamic Therapy in Cancer Stem Cell-Driven Tumorigenesis.

Cancer stem cells (CSCs) are essential for the growth of malignancies because they encourage resistance to cancer therapy and make metastasis and relapse easier. To effectively tackle the obstacles presented by CSCs, novel therapeutic approaches are required. Photodynamic therapy (PDT) is a promising treatment option for cancer cells, which uses light-sensitive medications that are activated by light wavelengths. This review investigates the use of PDT to overcome malignancies driven by CSCs that have innate resistance mechanisms. PDT works by causing tumor cells to accumulate photosensitizers

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… Targeting Glioma Stem Cell-Derived Pericytes Disrupts the Blood-Tumor Barrier and Improves Chemotherapeutic Efficacy Cell Stem Cell 2017 21 591 603.e4 10.1016/j.stem.2017.10.002 29100012 PMC5687837 97. Wu F. Yang J. Liu J. Wang Y. Mu J. Zeng Q. Deng S. Zhou H. …

Plasma cell targeting with the anti-CD38 antibody daratumumab in myalgic encephalomyelitis/chronic fatigue syndrome-a clinical pilot study.

BackgroundMyalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) entails low quality of life for patients and massive societal costs. There is an urgent need for elucidation of disease mechanisms and for rational treatment. Our working hypothesis is that ME/CFS in a subgroup of patients is associated with functional autoantibodies emerging after an infection, and that plasma-cell depletion with transient reductions in serum immunoglobulins will have a beneficial effect on patients' symptoms.ObjectiveTo evaluate feasibility and toxicity of plasma-cell targeting treatment using the subcutan

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… Diversity of detected autoantibodies was evident ( 60 ), and staining seemed to co-localize with pericytes and to some extent with endothelial cells. …

Mechanistic Insights into the Metabolic Pathways and Neuroprotective Potential of Pentacyclic Triterpenoids: In-Depth Analysis of Betulin, Betulinic, and Ursolic Acids.

Due to their complexity, both genotypic and phenotypic, neurodegenerative diseases are one of the main causes of death globally nowadays. Among phytochemicals of high scientific interest, based on experimental studies, pentacyclic triterpenoids (TTs), including mainly betulin, betulinic, and ursolic acid, became targets of scientific research in recent years, especially in terms of their biological activity and pharmacological potential. Due to their anti-inflammatory and antioxidant properties, as well as their involvement in cellular signal transductions, they have been observed to act as an

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… Their role in BBB function, interactions with endothelial cells, astrocytes, and pericytes, were recently described as their involvement in the modulation of BBB function in neuroinflammatory conditions identified in stroke or neurodegenerative diseases. …

Primary central nervous system lymphomas: EHA-ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up.

This EHA-ESMO Clinical Practice Guideline provides key recommendations for managing primary DLBCL of the CNS.The guideline covers clinical, imaging and pathological diagnosis, staging and risk assessment, treatment and follow-up.Algorithms for first-line and salvage treatments are provided.The author group encompasses a multidisciplinary group of experts from different institutions and countries in Europe.Recommendations are based on available scientific data and the authors' collective expert opinion.

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… The use of agents that can permeabilise tumour vessels and increase ChT penetration was recently investigated in patients with r/r PCNSL. 97 , 98 Tumour necrosis factor‐α coupled with cysteine–asparagine–glycine–arginine–cysteine–glycine peptide (NGR‐hTNF) targets CD13+ pericytes and endothelial cells …

Биологическая роль мономеров традиционной китайской медицины в нейронных расстройствах.

Традиционная китайская медицина (TCM) является биоактивным соединением, извлекаемым из китайских травяных лекарственных препаратов, обладающих определенной биологической активностью и фармакологическими последствиями, и привлекла большое внимание к лечению нейронных заболеваний. Однако применение мономеров ТХМ ограничено их низкой растворимостью и низкой способностью пересекать барьер кровеносного мозга (ББД). Экзосомы представляют собой небольшие внеклеточные везикли (ЭМ) диаметром от 30 до 150 нм и могут использоваться в качестве носителей наркотиков, которые непосредственно предназначены дл

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… The BBB is a semi-permeable barrier composed of glial cells (astrocytes and microglia), pericytes, specialized brain microvascular endothelial cells (BMECs) connected by tight junctions, and a basement membrane [ 85 ]. …

Amino acid metabolism in primary bone sarcomas.

Primary bone sarcomas, including osteosarcoma (OS) and Ewing sarcoma (ES), are aggressive tumors with peak incidence in childhood and adolescence. The intense standard treatment for these patients consists of combined surgery and/or radiation and maximal doses of chemotherapy; a regimen that has not seen improvement in decades. Like other tumor types, ES and OS are characterized by dysregulated cellular metabolism and a rewiring of metabolic pathways to support the biosynthetic demands of malignant growth. Not only are cancer cells characterized by Warburg metabolism, or aerobic glycolysis, bu

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… Primary bone sarcomas grow in specialized and complex bone microenvironment that are highly vascularized and contain osteoclasts, osteoblasts, osteocytes, stromal cells (MSCs, fibroblasts), vascular cells (endothelial cells and pericytes), immune cells (macrophages, lymphocytes) ( 102 , 103 ), and a …

The Trinity: Interplay among Cancer Cells, Fibroblasts, and Immune Cells in Pancreatic Cancer and Implication of CD8+ T Cell-Orientated Therapy.

The microenvironment in tumors is complicated and is constituted by different cell types and stromal proteins. Among the cell types, the abundance of cancer cells, fibroblasts, and immune cells is high and these cells work as the "Trinity" in promoting tumorigenesis. Although unidirectional or bidirectional crosstalk between two independent cell types has been well characterized, the multi-directional interplays between cancer cells, fibroblasts, and immune cells in vitro and in vivo are still unclear. We summarize recent studies in addressing the interaction of the "Trinity" members in the tu

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… This heterogenicity starts from the origins of CAFs, which may be resident fibroblasts, pancreatic stellate cells, adipocytes, pericytes, endothelial cells, and mesenchymal stem cells. In terms of subtype heterogenicity, the antigen-presenting CAF (apCAF) [ 38 , 67 , 68 ] is also present. …

Mesenchymal Stem Cell-Based Therapy for Kidney Disease: A Review of Clinical Evidence.

Mesenchymal stem cells form a population of self-renewing, multipotent cells that can be isolated from several tissues. Multiple preclinical studies have demonstrated that the administration of exogenous MSC could prevent renal injury and could promote renal recovery through a series of complex mechanisms, in particular via immunomodulation of the immune system and release of paracrine factors and microvesicles. Due to their therapeutic potentials, MSC are being evaluated as a possible player in treatment of human kidney disease, and an increasing number of clinical trials to assess the safety

Guided immunotherapy for residual solid tumor: integrating platelets and CAR T cells to reduce post-surgical recurrence.

Postoperative recurrence remains a major obstacle to durable remission in patients with solid tumors, even after complete macroscopic resection. Growing evidence suggests that surgery creates a transient yet highly permissive biological window characterized by inflammatory signaling, coagulation activation, endothelial disruption, and systemic immune suppression. Together, these processes foster a protective niche that enables microscopic residual disease to evade immune surveillance and initiate metastatic outgrowth. Although modern adjuvant therapies have improved outcomes, their effectivene

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… in fibrotic tumors HA–CD44, TLR4, integrin signaling Context-dependent [ 66 , 67 ] Endothelial cells/TECs Build vascular ECM scaffolds and remodel the endothelial basement membrane Neovascularization and metastatic niche formation VEGF, collagen IV, fibronectin, biglycan Mostly pro-tumor [ 68 , 69 ] Pericytes … tumors | HA–CD44, TLR4, integrin signaling | Context-dependent | [ 66 , 67 ] Endothelial cells/TECs | Build vascular ECM scaffolds and remodel the endothelial basement membrane | Neovascularization and metastatic niche formation | VEGF, collagen IV, fibronectin, biglycan | Mostly pro-tumor | [ 68 , 69 ] Pericytes …

EP300 as a Molecular Integrator of Fibrotic Transcriptional Programs.

Fibrosis is a condition characterized by the excessive accumulation of extracellular matrix proteins in tissues, leading to organ dysfunction and failure. Recent studies have identified EP300, a histone acetyltransferase, as a crucial regulator of the epigenetic changes that contribute to fibrosis. In fact, EP300-mediated acetylation of histones alters global chromatin structure and gene expression, promoting the development and progression of fibrosis. Here, we review the role of EP300-mediated epigenetic regulation in multi-organ fibrosis and its potential as a therapeutic target. We discuss

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… Myofibroblasts refer to a cellular phenotype characterized by stellate-shaped cells with high levels of intracellular proteins such as non-muscle myosin, alpha smooth-muscle actin (αSMA), and vimentin and differentiated from diverse sources (pericytes, endothelial cells, fibrocytes, epithelial cells, …

Cancer-Associated Thrombosis: Epidemiology, Pathophysiological Mechanisms, Treatment, and Risk Assessment.

Cancer patients represent a growing population with drastically difficult care and a lowered quality of life, especially due to the heightened risk of vast complications. Thus, it is well established so far that one of the most prominent complications in individuals with cancer is venous thromboembolism. Since there are various improved methods for screening and diagnosing cancer and its complications, the incidence of cancer-associated thrombosis has been on the rise in recent years. Therefore, the high mortality and morbidity rates among these patients are not a surprise. Consequently, there

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… 85 Heraudeau 86 and Tinholt et al 87 Direct Mechanisms of Cancer-Associated Thrombosis Tissue factor The protein known as tissue factor (TF) is widely recognized as a procoagulant that originates from tumors, but it is expressed in large quantities on subendothelial cells, including fibroblasts, pericytes …

Clinical Efficacy and Potential Mechanisms of Acupoint Stimulation Combined With Chemotherapy in Combating Cancer: A Review and Prospects.

Although chemotherapy is the first-line treatment strategy for a variety of tumors, its side effects have limited its efficacy. This review summarizes the progress on the use of acupoint stimulation to combat chemotherapy-associated side effects, including chemotherapy-induced peripheral neuropathy (CIPN), cognitive impairment (CICI), and gastrointestinal toxicity (GI), as well as myelosuppression and immunosuppression. It was found that acupoint stimulation attenuated CIPN and GI by modulating the 5-hydroxytryptamine system in dorsal root ganglia, the dorsal horn of the spinal cord, and the d

A Drug Screening Reveals Minocycline Hydrochloride as a Therapeutic Option to Prevent Breast Cancer Cells Extravasation across the Blood-Brain Barrier.

Among breast cancer (BC) patients, 15-25% develop BC brain metastases (BCBM), a severe condition due to the limited therapeutic options, which points to the need for preventive strategies. We aimed to find a drug able to boost blood-brain barrier (BBB) properties and prevent BC cells (BCCs) extravasation, among PI3K, HSP90, and EGFR inhibitors and approved drugs. We used BCCs (4T1) and BBB endothelial cells (b.End5) to identify molecules with toxicity to 4T1 cells and safe for b.End5 cells. Moreover, we used those cells in mixed cultures to perform a high-throughput microscopy screening of dru

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… Neurovascular Unit: A Focus on Pericytes Mol. Neurobiol. 2012 45 327 347 10.1007/s12035-012-8244-2 22371274 58. Koul D. Fu J. Shen R. LaFortune T.A. Wang S. Tiao N. Kim Y.-W. Liu J.-L. Ramnarian D. Yuan Y. …

Angiogenesis and Anti-Angiogenic Treatment in Prostate Cancer: Mechanisms of Action and Molecular Targets.

Prostate cancer (PC) is the most common cancer in men and the second leading cause of cancer-related death worldwide. Many therapeutic advances over the last two decades have led to an improvement in the survival of patients with metastatic PC, yet the majority of these patients still succumb to their disease. Antiagiogenic therapies have shown substantial benefits for many types of cancer but only a marginal benefit for PC. Ongoing clinical trials investigate antiangiogenic monotherapies or combination therapies. Despite the important role of angiogenesis in PC, clinical trials in refractory

Autoimmune Rheumatic Diseases and Vascular Function: The Concept of Autoimmune Atherosclerosis.

Autoimmune rheumatic diseases (AIRDs) with unknown etiology are increasing in incidence and prevalence. Up to 5% of the population is affected. AIRDs include rheumatoid arthritis, system lupus erythematosus, systemic sclerosis, and Sjögren's syndrome. In patients with autoimmune diseases, the immune system attacks structures of its own body, leading to widespread tissue and organ damage, which, in turn, is associated with increased morbidity and mortality. One third of the mortality associated with autoimmune diseases is due to cardiovascular diseases. Atherosclerosis is considered the main un

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… Strengthening tight junctions of retinal microvascular endothelial cells by pericytes under normoxia and hypoxia involving angiopoietin-1 signal way Eye 2007 21 1501 1510 10.1038/sj.eye.6702716 17332770 175. Hughes A.D. Wong T.Y. Witt N. Evans R. Thom S.A.M. Klein B.E. Chaturvedi N. Klein R. …