Multipotent/pluripotent stem cell populations in stromal tissues and peripheral blood: exploring diversity, potential, and therapeutic applications

Stem Cell Research & Therapy, Год журнала: 2024, Номер 15(1)

Опубликована: Май 12, 2024

The concept of "stemness" incorporates the molecular mechanisms that regulate unlimited self-regenerative potential typical undifferentiated primitive cells. These cells possess unique ability to navigate cell cycle, transitioning in and out quiescent G0 phase, hold capacity generate diverse phenotypes. Stem cells, as precursors endow with extraordinary regenerative capabilities, exhibit a heterogeneous tissue-specific distribution throughout human body. identification characterization distinct stem populations across various tissues have revolutionized our understanding tissue homeostasis regeneration. From hematopoietic nervous musculoskeletal systems, presence underlines complex adaptability multicellular organisms. Recent investigations revealed cohort non-hematopoietic (non-HSC), primarily within bone marrow other stromal tissue, alongside established (HSC). Among these non-HSC, rare subset exhibits pluripotent characteristics. In vitro vivo studies demonstrated remarkable differentiation putative known by names including multipotent adult progenitor (MAPC), marrow-isolated multilineage inducible (MIAMI), small blood (SBSC), very embryonic-like (VSELs), differentiating stress enduring (MUSE). nomenclatures assigned may arise from different origins or varied experimental methodologies. This review aims present comprehensive comparison subpopulations multipotent/pluripotent derived tissues. By analysing isolation techniques surface marker expression associated populations, we aim delineate similarities distinctions among tissue-derived Understanding nuances is critical for unlocking their therapeutic advancing medicine. future research should prioritize standardization methodologies collaborative shared laboratory environments. approach could mitigate variability outcomes foster scientific partnerships fully exploit

Язык: Английский

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

Cellular and Molecular Life Sciences, Год журнала: 2024, Номер 81(1)

Опубликована: Янв. 23, 2024

In embryonic stem cells (ESCs) and induced pluripotent (iPSCs), the expression of an RNA-binding pluripotency-relevant protein, LIN28, absence its antagonist, tumor-suppressor microRNA (miRNA) let-7, play a key role in maintaining pluripotency. Muse are non-tumorigenic pluripotent-like residing bone marrow, peripheral blood, organ connective tissues as surface marker SSEA-3(+). They express pluripotency genes, differentiate into triploblastic-lineage cells, self-renew at single cell level. do not LIN28 but let-7 higher levels than iPSCs. we demonstrated that inhibited PI3K-AKT pathway, leading to sustainable regulator KLF4 well downstream POU5F1, SOX2, NANOG. Let-7 also suppressed proliferation glycolysis by inhibiting suggesting involvement non-tumorigenicity. Furthermore, MEK/ERK pathway is controlled may have pivotal self-renewal suppression senescence. The system found which tumor suppressor tunes might be rational conferring both pluripotency-like properties low risk for tumorigenicity.

Язык: Английский

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Safety and Clinical Effects of a Muse Cell-Based Product in Patients With Amyotrophic Lateral Sclerosis: Results of a Phase 2 Clinical Trial

Cell Transplantation, Год журнала: 2023, Номер 32

Опубликована: Янв. 1, 2023

Amyotrophic lateral sclerosis (ALS) is characterized by progressive loss of motor neurons. Multilineage-differentiating stress-enduring (Muse) cells are unique endogenous stem that show therapeutic effects on function in ALS mouse models. We conducted a single-center open phase II clinical trial to evaluate the safety and repeated intravenous injections an allogenic Muse cell-based product, CL2020, patients with ALS. Five received CL2020 intravenously once month for total six doses. The primary endpoints were tolerability, secondary endpoint was rate change Revised Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score. In addition, serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), sphingosine-1-phosphate (S1P), cerebrospinal fluid chitotriosidase-1 (CHIT-1), neurofilament light chain (NfL) levels evaluated. treatment highly tolerated without serious side effects. ALSFRS-R score trended upward at 12 months post-CL2020 compared 3 pre-administration, but difference not statistically significant. Among five diagnosed ALS, three exhibited decrease change, one demonstrated increase, another showed no change. patients’ IL-6 TNF-α CHIT-1 NfL increased up 6 post-treatment; however, their S1P continuously decreased over months. These findings indicate favorable profile therapy. near future, double-blind study larger number should be confirm efficacy CL2020.

Язык: Английский

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Human post-implantation blastocyst-like characteristics of Muse cells isolated from human umbilical cord

Cellular and Molecular Life Sciences, Год журнала: 2024, Номер 81(1)

Опубликована: Июль 11, 2024

Abstract Muse cells, identified as cells positive for the pluripotent surface marker SSEA-3, are pluripotent-like endogenous stem located in bone marrow (BM), peripheral blood, and organ connective tissues. The detailed characteristics of SSEA-3(+) extraembryonic tissue, however, unknown. Here, we demonstrated that similar to human-adult tissue-Muse collected from BM, adipose dermis SSEA-3(+), human-umbilical cord (UC)-SSEA-3(+) express pluripotency markers, differentiate into triploblastic-lineage at a single cell level, migrate damaged exhibit low telomerase activity non-tumorigenicity. Notably, ~ 20% human-UC-SSEA-3(+) were negative X-inactive specific transcript (XIST), naïve characteristic, whereas all human adult XIST-positive. Single-cell RNA sequencing revealed gene expression profile was more post-implantation blastocysts than cells. DNA methylation level showed same trend, notably, levels genes particularly related differentiation lower Furthermore, newly markers extraembryonic-, germline-, hematopoietic-lineages after induction vitro respond only partially induction. Among various stem/progenitor living bodies, those properties state have not yet been found humans. Easily accessible may be valuable tool studying early-stage development reproductive medicine.

Язык: Английский

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Macrophage- and pluripotent-like reparative Muse cells are unique endogenous stem cells distinct from other somatic stem cells

Frontiers in Bioengineering and Biotechnology, Год журнала: 2025, Номер 13

Опубликована: Март 27, 2025

Muse cells are endogenous reparative stem with dual characteristics: pluripotent-like and macrophage-like. They can be identified by the pluripotent surface marker stage-specific embryonic antigen-3-positive (SSEA-3 (+)) in bone marrow, peripheral blood, various organs, including umbilical cord amnion. differentiate into ectodermal, endodermal, mesodermal lineage cells, self-renew, selectively migrate to damaged sites sensing one of universal tissue damage signals, sphingosine-1-phosphate (S1P). At these sites, they phagocytose damaged/apoptotic same cell type as phagocytosed cells. In this manner, replace healthy, functioning thereby repairing tissues. Due their specific immunosuppressive immunotolerant mechanism, clinical trials have been conducted for acute myocardial infarction (AMI), subacute ischemic stroke, epidermolysis bullosa, amyotrophic lateral sclerosis (ALS), cervical spinal injury, neonatal hypoxic-ischemic encephalopathy (HIE), COVID-19 respiratory distress syndrome. These involved intravenous injection ∼1.5 × 10 7 donor without human leukocyte antigen (HLA) matching or immunosuppressant treatment, demonstrated safety therapeutic efficacy. Thus, treatment does not require gene manipulation, differentiation induction, surgical intervention. unique characteristics distinguish from other somatic such mesenchymal VSEL marrow-isolated adult multi-lineage inducible (MIAMI)

Язык: Английский

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Donor Muse Cell Treatment Without HLA-Matching Tests and Immunosuppressant Treatment

Stem Cells Translational Medicine, Год журнала: 2024, Номер 13(6), С. 532 - 545

Опубликована: Апрель 1, 2024

The strength of stem cell therapy is the regeneration tissues by synergistic pleiotropic effects. Among many types, mesenchymal cells (MSCs) that are comprised heterogenous population widely used for clinical applications with expectation bystander Muse pluripotent-like/macrophage-like distributed in bone marrow, peripheral blood, and organ connective as positive pluripotent surface marker stage-specific-embryonic antigen -3. comprise ~1% to several percent MSCs. While MSCs share characteristics, such expression their effects, exhibit unique characteristics not observed These include selective homing damaged tissue after intravenous injection rather than being trapped lung like MSCs, replacement a wide range damaged/apoptotic differentiation through phagocytosis, long-lasting immunotolerance donor use. In this review, we focus on basic properties clarified preclinical studies trials conducted donor-Muse without HLA-matching tests or immunosuppressant treatment. considered differentiate into osteogenic, chondrogenic, adipogenic cells, whereas has long been debated. may provide clues wide-ranging potential low frequency. Furthermore, utilization novel strategy

Язык: Английский

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Stem Cell Therapy for Acute/Subacute Ischemic Stroke with a Focus on Intraarterial Stem Cell Transplantation: From Basic Research to Clinical Trials

Bioengineering, Год журнала: 2022, Номер 10(1), С. 33 - 33

Опубликована: Дек. 27, 2022

Stem cell therapy for ischemic stroke holds great promise the treatment of neurological impairment and has moved from laboratory into early clinical trials. The mechanism action stem includes bystander effect replacement. plays an important role in acute to subacute phase, replacement chronic phase. Intraarterial (IA) transplantation is less invasive than intraparenchymal can provide more cells affected brain region intravenous transplantation. However, transplanted migration was reported be insufficient, few were retained extended period. Therefore, considered main IA In most trials, performed during phases. Although trials demonstrated safety, they did not demonstrate satisfactory efficacy improving patient outcomes. To increase efficacy, increased production long surviving effective would crucial. Given lack knowledge on this subject, we review summarize mechanisms recent advancements preclinical studies information guidance further advancement acute/subacute phase stroke.

Язык: Английский

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Intravenous Administration of Human Muse Cells Ameliorates Deficits in a Rat Model of Subacute Spinal Cord Injury

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(19), С. 14603 - 14603

Опубликована: Сен. 27, 2023

Multilineage-differentiating stress-enduring (Muse) cells are newly established pluripotent stem cells. The aim of the present study was to examine potential systemic administration Muse as an effective treatment for subacute SCI. We intravenously administered clinical product "CL2020" containing a rat model two weeks after mid-thoracic spinal cord contusion. Eight experimental animals received CL2020, and twelve vehicle. Behavioral analyses were conducted over 20 weeks. Histological evaluations performed. After observation, diphtheria toxin three CL2020-treated selectively ablate human cell functions. Hindlimb motor functions significantly improved from 6 CL2020. cystic cavity smaller in CL2020 group. Furthermore, larger numbers descending 5-HT fibers preserved distal cord. considered have differentiated into neuronal neural injured Neuronal identified gray white matter, respectively. Importantly, these effects reversed by selective ablation toxin. Intravenously facilitated therapeutic severe injury.

Язык: Английский

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Human Muse cells isolated from preterm- and term-umbilical cord delivered therapeutic effects in rat bleomycin-induced lung injury model without immunosuppressant

Stem Cell Research & Therapy, Год журнала: 2024, Номер 15(1)

Опубликована: Май 21, 2024

Abstract Background Bleomycin (BLM)-induced lung injury is characterized by mixed histopathologic changes with inflammation and fibrosis, such as observed in human patients bronchopulmonary dysplasia, idiopathic pulmonary chronic obstructive disease. Although no curative therapies for these diseases exist, stem cell therapy has emerged a potential therapeutic option. Multilineage-differentiating stress-enduring (Muse) cells are endogenous pluripotent- macrophage-like distributed various adult fetal tissues stage-specific embryonic antigen-3-positive cells. They selectively home to damaged tissue sensing sphingosine-1-phosphate replace the damaged/apoptotic vivo differentiation. Clinical trials some suggest safety efficacy of intravenously injected leukocyte antigen-mismatched allogenic Muse from bone marrow (BM) without immunosuppressant. Here, we evaluated effects preterm term umbilical cord (UC), BM rat BLM-induced model. Methods Rats were endotracheally administered BLM induce on day 0. On 3, UC-Muse, or BM-Muse immunosuppressants, rats subjected analysis 21. Body weight, serum surfactant protein D (SP-D) levels, oxygen saturation (SpO 2 ) monitored. Histopathologic scoring Ashcroft modified American Thoracic Society document scales, quantitative characterization engrafted cells, RNA sequencing analysis, vitro migration assay infused performed. Results preterm- term-UC-Muse exhibited significantly better recovery based weight loss, SP-D SpO , scores, higher rate both homing alveolar marker expression (podoplanin prosurfactant protein-C) than receiving preterm-UC-Muse showed statistically superior results those many measures. These findings thought be due genes related migration, differentiation, adhesion. Conclusion Preterm UC-Muse deliver more efficient UC- treating

Язык: Английский

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Investigating the Potential of Multilineage Differentiating Stress-Enduring Cells for Osteochondral Healing

Cartilage, Год журнала: 2024, Номер unknown

Опубликована: Июнь 17, 2024

Objective Multilineage differentiating stress-enduring (Muse) cells, a pluripotent stem cell subset of mesenchymal cells (MSCs), have shown promise for various tissue repairs due to their stress tolerance and multipotent capabilities. We aimed investigate the differentiation potential in vitro, dynamics vivo, reparative contribution Muse osteochondral lesions. Design Labeled MSCs were cultured sorted into non-Muse (MSCs without cells) groups. These then formed spheroids, chondrogenic was assessed vitro. Twenty-one immunocompromised mice used as vivo models Live imaging, macroscopic evaluation, histological immunohistochemical analyses conducted at 4- 8-week time points. Results spheroids formed, which larger stained more intensely with toluidine blue than indicating better differentiation. imaging confirmed luminescence all 4-week model knees, but only few knees 8 weeks, suggesting persistence. Macroscopically histologically, no significant differences observed between groups 4 weeks; however, both showed cartilage repair that vehicle group weeks. No collagen type II generation repaired tissues. Conclusion The implantation resulted healing lesions controls, had higher vitro cells.

Язык: Английский

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