Structural reconstruction of mouse acute aortic dissection by intravenously administered human Muse cells without immunosuppression.

Background: Stanford type B-acute aortic dissection (type B-AAD) is often life-threatening without invasive surgery. Multilineage-differentiating stress enduring cell (Muse cells), which comprise several percent of mesenchymal stem cells (MSCs), are endogenous pluripotent-like stem cells that selectively home to damaged tissue and replace damaged/apoptotic cells by in-vivo differentiation.

Methods: Mortality, aortic diameter expansion, cell localization, cell differentiation, and inflammation of the dissected aorta were evaluated in type B-AAD model mice intravenously injected with human-Muse cells, -elastin-knockdown (KD)-Muse cells, -human leukocyte antigen-G (HLA-G)-KD-Muse cells, or MSCs, all without immunosuppressant.

New rat model of spinal cord infarction with long-lasting functional disabilities generated by intraspinal injection of endothelin-1.

Background: The current method for generating an animal model of spinal cord (SC) infarction is highly invasive and permits only short-term observation, typically limited to 28 days.

Objective: We aimed to establish a rat model characterised by long-term survival and enduring SC dysfunction by inducing selective ischaemic SC damage.

Methods: In 8-week-old male Wistar rats, a convection-enhanced delivery technique was applied to selectively deliver endothelin-1 (ET-1) to the anterior horn of the SC at the Th13 level, leading to SC infarction.

Tumor suppressor let-7 acts as a key regulator for pluripotency gene expression in Muse cells.

In embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), the expression of an RNA-binding pluripotency-relevant protein, LIN28, and the absence of its antagonist, the tumor-suppressor microRNA (miRNA) let-7, play a key role in maintaining pluripotency. Muse cells are non-tumorigenic pluripotent-like stem cells residing in the bone marrow, peripheral blood, and organ connective tissues as pluripotent surface marker SSEA-3(+). They express pluripotency genes, differentiate into triploblastic-lineage cells, and self-renew at the single cell level.

Intravenously engrafted human multilineage-differentiating stress-enduring (Muse) cells rescue erectile function after rat cavernous nerve injury.

Objective: To evaluate the effect of intravenous administration of human multilineage-differentiating stress-enduring (Muse) cells on rat postoperative erectile dysfunction (ED) with cavernous nerve (CN) injury without an immunosuppressant.

Materials And Methods: Male Sprague-Dawley rats were randomised into three groups after CN crush injury. Either human-Muse cells, non-Muse mesenchymal stem cells (MSCs) (both 1.

Meta-analysis of senescent cell secretomes to identify common and specific features of the different senescent phenotypes: a tool for developing new senotherapeutics.

DNA damage resulting from genotoxic injury can initiate cellular senescence, a state characterized by alterations in cellular metabolism, lysosomal activity, and the secretion of factors collectively known as the senescence-associated secretory phenotype (SASP). Senescence can have beneficial effects on our bodies, such as anti-cancer properties, wound healing, and tissue development, which are attributed to the SASP produced by senescent cells in their intermediate stages. However, senescence can also promote cancer and aging, primarily due to the pro-inflammatory activity of SASP.

Systemic administration of clinical-grade multilineage-differentiating stress-enduring cells ameliorates hypoxic-ischemic brain injury in neonatal rats.

Multilineage-differentiating stress-enduring (Muse) cells are endogenous reparative pluripotent stem cells present in the bone marrow, peripheral blood, and organ connective tissues. We assessed the homing and therapeutic effects of systemically administered nafimestrocel, a clinical-grade human Muse cell-based product, without immunosuppressants in a neonatal hypoxic-ischemic (HI) rat model. HI injury was induced on postnatal day 7 (P7) and was confirmed by T2-weighted magnetic resonance imaging on P10.

Comparison of the Anti-Inflammatory Effects of Mouse Adipose- and Bone-Marrow-Derived Multilineage-Differentiating Stress-Enduring Cells in Acute-Phase Spinal Cord Injury.

Spinal cord injury (SCI) is a serious neurological disorder, with the consequent disabilities conferred by this disorder typically persisting for life. Multilineage-differentiating stress-enduring (Muse) cells are endogenous stem cells that can be collected from various tissues as well as from mesenchymal stem cells (MSCs); additionally, these Muse cells are currently being used in clinical trials. The anti-inflammatory effect of stem cell transplantation prevents secondary injuries of SCI; however, its effect on Muse cells remains unclear.

Endogenous reparative pluripotent Muse cells with a unique immune privilege system: Hint at a new strategy for controlling acute and chronic inflammation.

Multilineage-differentiating stress enduring (Muse) cells, non-tumorigenic endogenous pluripotent stem cells, reside in the bone marrow (BM), peripheral blood, and connective tissue as pluripotent surface marker SSEA-3(+) cells. They express other pluripotent markers, including Nanog, Oct3/4, and Sox2 at moderate levels, differentiate into triploblastic lineages, self-renew at a single cell level, and exhibit anti-inflammatory effects. Cultured mesenchymal stromal cells (MSCs) and fibroblasts contain several percent of SSEA-3(+)-Muse cells.

Single-cell RNA sequencing reveals different signatures of mesenchymal stromal cell pluripotent-like and multipotent populations.

Somatic stem cells are advantageous research targets for understanding the properties required to maintain stemness. Human bone marrow-mesenchymal stromal cells (BM-MSCs) were separated into pluripotent-like SSEA-3(+) Muse cells (Muse-MSCs) and multipotent SSEA-3(-) MSCs (MSCs) and were subjected to single-cell RNA sequencing analysis. Compared with MSCs, Muse-MSCs exhibited higher expression levels of the p53 repressor ; signal acceptance-related genes EGF, VEGF, PDGF, WNT, TGFB, INHB, and CSF; ribosomal protein; and glycolysis and oxidative phosphorylation.

Naïve pluripotent-like characteristics of non-tumorigenic Muse cells isolated from human amniotic membrane.

Multilineage-differentiating stress-enduring (Muse) cells are non-tumorigenic pluripotent-like stem cells that exhibit triploblastic differentiation and self-renewability at the single-cell level, and are collectable as pluripotent surface marker SSEA-3(+) from the bone marrow (BM), peripheral blood, and organ connective tissues. SSEA-3(+) cells from human amniotic membrane mesenchymal stem cells (hAMSCs) were compared with hBM-Muse cells. Similar to hBM-Muse cells, hAMSC-SSEA-3(+) cells expressed pluripotency genes (OCT3/4, NANOG, and SOX2), differentiated into triploblastic cells from a single cell, self-renewed, and exhibited non-tumorigenicity.

Phagocytosing differentiated cell-fragments is a novel mechanism for controlling somatic stem cell differentiation within a short time frame.

Stem cells undergo cytokine-driven differentiation, but this process often takes longer than several weeks to complete. A novel mechanism for somatic stem cell differentiation via phagocytosing 'model cells' (apoptotic differentiated cells) was found to require only a short time frame. Pluripotent-like Muse cells, multipotent mesenchymal stem cells (MSCs), and neural stem cells (NSCs) phagocytosed apoptotic differentiated cells via different phagocytic receptor subsets than macrophages.

Inhibition of Gap Junctional Intercellular Communication Upregulates Pluripotency Gene Expression in Endogenous Pluripotent Muse Cells.

Gap junctions (GJ) are suggested to support stem cell differentiation. The Muse cells that are applied in clinical trials are non-tumorigenic pluripotent-like endogenous stem cells, can be collected as stage-specific embryonic antigen 3 (SSEA-3+) positive cells from multiple tissues, and show triploblastic differentiation and self-renewability at a single cell level. They were reported to up-regulate pluripotency gene expression in suspension.

Effects of human Muse cells on bladder inflammation, overactivity, and nociception in a chemically induced Hunner-type interstitial cystitis-like rat model.

Introduction And Hypothesis: We investigated the effects of locally administered human multilineage-differentiating stress enduring (Muse) cells, nontumorigenic pluripotent-like endogenous stem cells, on bladder tissues, function, and nociceptive behavior in a chemically induced Hunner-type interstitial cystitis (HIC)-like rat model without immunosuppressant.

Methods: Chemical cystitis was induced by intravesical instillation of 0.2 N hydrochloride (HCl) for 15 min in female F344 rats.

Human Muse cells reduce myocardial infarct size and improve cardiac function without causing arrythmias in a swine model of acute myocardial infarction.

Background: We recently reported that multilineage-differentiating stress enduring (Muse) cells intravenously administered after acute myocardial infarction (AMI), selectively engrafted to the infarct area, spontaneously differentiated into cardiomyocytes and vessels, reduced the infarct size, improved the left ventricular (LV) function and remodeling in rabbits. We aimed to clarify the efficiency of Muse cells in a larger animal AMI model of mini-pigs using a semi-clinical grade human Muse cell product.

Method And Result: Mini-pigs underwent 30 min of coronary artery occlusion followed by 2 weeks of reperfusion.

Stem cell therapy for acute myocardial infarction - focusing on the comparison between Muse cells and mesenchymal stem cells.

Rapid percutaneous coronary intervention for acute myocardial infarction (AMI) reduces acute mortality, but there is an urgent need for treatment of left ventricular dysfunction and remodeling after AMI to improve the prognosis. The myocardium itself does not have a high regenerative capacity, and it is important to minimize the loss of cardiomyocytes and maintain the cardiac function after AMI. To overcome these problems, attention has been focused on myocardial regeneration therapy using cells derived from bone marrow.

Cell-based treatment for perinatal hypoxic-ischemic encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) is a major cause of acute neonatal brain injury and can lead to disabling long-term neurological complications. Treatment for HIE is limited to supportive care and hypothermia within 6 h injury which is reserved for full-term infants. Preclinical studies suggest the potential for cell-based therapies as effective treatments for HIE.

Non-Tumorigenic Pluripotent Reparative Muse Cells Provide a New Therapeutic Approach for Neurologic Diseases.

Muse cells are non-tumorigenic endogenous reparative pluripotent cells with high therapeutic potential. They are identified as cells positive for the pluripotent surface marker SSEA-3 in the bone marrow, peripheral blood, and connective tissue. Muse cells also express other pluripotent stem cell markers, are able to differentiate into cells representative of all three germ layers, self-renew from a single cell, and are stress tolerant.

Isolation and characterization of bone marrow-derived mesenchymal stem cells in Xenopus laevis.

Mesenchymal stem cells (MSCs) are multipotent cells that exist in mesenchymal tissues such as bone marrow and are able to differentiate into osteocytes, chondrocytes, and adipocytes. MSCs are generally collected as adherent cells on a plastic dish, and are positive for markers such as CD44, CD73, CD90, CD105 and CD166, and negative for CD11b, CD14, CD19, CD31, CD34, CD45, CD79a and HLA-DR. MSCs have been established from many kinds of mammals, but MSCs from amphibians have not yet been reported.