Human Muse Cells Reconstruct Neuronal Circuitry in Subacute Lacunar Stroke Model

Uchida, Hiroki; Niizuma, Kuniyasu; Kushida, Yoshihiro; Wakao, Shohei; Tominaga, Teiji; Borlongan, Cesario V.; Dezawa, Mari

doi:10.1161/strokeaha.116.014950

Cited by 92 publications

(123 citation statements)

References 33 publications

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“…Therefore, Muse cells, in both the circulation and tissues, can selectively accumulate at the damaged site. After homing, Muse cells spontaneously differentiate into tissue-constituent cells and replenish damaged/lost cells to participate in tissue repair, as demonstrated following intravenous injection of exogenous Muse cells into animal models of stroke, encephalitis, acute myocardial infarction, renal failure, and liver damage 11 – 15 . Clinical data from patients with acute myocardial infarction and stroke indicate that the serum S1P levels increase prior to the increase in the number of endogenous PB-Muse cells after onset and this increase in the acute phase significantly correlates with functional recovery at 6 months, supporting a reparative function of Muse cells in vivo 11 , 16 .…”

Section: Introductionmentioning

confidence: 99%

A Novel Type of Stem Cells Double-Positive for SSEA-3 and CD45 in Human Peripheral Blood

et al. 2020

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Peripheral blood (PB) contains several types of stem/progenitor cells, including hematopoietic stem and endothelial progenitor cells. We identified a population positive for both the pluripotent surface marker SSEA-3 and leukocyte common antigen CD45 that comprises 0.04% ± 0.003% of the mononuclear cells in human PB. The average size of the SSEA-3(+)/CD45(+) cells was 10.1 ± 0.3 µm and ∼22% were positive for CD105, a mesenchymal marker; ∼85% were positive for CD19, a B cell marker; and ∼94% were positive for HLA-DR, a major histocompatibility complex class II molecule relevant to antigen presentation. These SSEA-3(+)/CD45(+) cells expressed the pluripotency markers Nanog, Oct3/4, and Sox2, as well as sphingosine-1-phosphate (S1P) receptor 2, and migrated toward S1P, although their adherence and proliferative activities in vitro were low. They expressed NeuN at 7 d, Pax7 and desmin at 7 d, and alpha-fetoprotein and cytokeratin-19 at 3 d when supplied to mouse damaged tissues of the brain, skeletal muscle and liver, respectively, suggesting the ability to spontaneously differentiate into triploblastic lineages compatible to the tissue microenvironment. Multilineage-differentiating stress enduring (Muse) cells, identified as SSEA-3(+) in tissues such as the bone marrow and organ connective tissues, express pluripotency markers, migrate to sites of damage via the S1P-S1P receptor 2 system, and differentiate spontaneously into tissue-compatible cells after homing to the damaged tissue where they participate in tissue repair. After the onset of acute myocardial infarction and stroke, patients are reported to have an increase in the number of SSEA-3(+) cells in the PB. The SSEA-3(+)/CD45(+) cells in the PB showed similarity to tissue-Muse cells, although with difference in surface marker expression and cellular properties. Thus, these findings suggest that human PB contains a subset of cells that are distinct from known stem/progenitor cells, and that CD45(+)-mononuclear cells in the PB comprise a novel subpopulation of cells that express pluripotency markers.

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Section: Introductionmentioning

confidence: 99%

A Novel Type of Stem Cells Double-Positive for SSEA-3 and CD45 in Human Peripheral Blood

et al. 2020

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“…Muse cells were originally identified as cells that are resistant to long-term trypsin incubation and are known as cells that are double positive for the pluripotent surface marker, stage-specific embryonic antigen-3 (SSEA-3), and CD105, and that have the capacity for self-renewal and triploblastic differentiation from a single cell [6]. The applicability of Muse cells for regenerative treatments has been suggested in disease models of liver damage, stroke, skin ulcers related to diabetes mellitus, and osteochondral defects [9], [10], [11], [12].…”

Section: Introductionmentioning

confidence: 99%

Multilineage-differentiating stress-enduring (Muse)-like cells exist in synovial tissue

Toyoda

Sato

Takahashi

et al. 2019

Regenerative Therapy

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IntroductionCartilage regeneration is a promising therapy for restoring joint function in patients with cartilage defects. The limited availability of autologous chondrocytes or chondrogenic progenitor cells is an obstacle to its clinical application. We investigated the existence and chondrogenic potential of synovial membrane-derived multilineage-differentiating stress-enduring (Muse)-like cells as an alternative cell source for cartilage regeneration.MethodsCells positive for stage-specific embryonic antigen-3 (SSEA-3), a marker of Muse cells, were isolated from the synovial membranes of 6 of 8 patients (median age, 53.5 years; range 36–72 years) by fluorescence-activated cell sorting. SSEA-3-positive cells were cultured in methylcellulose to examine their ability to form Muse clusters that are similar to the embryoid bodies formed by human embryonic stem cells. Muse clusters were expanded and chondrogenic potential of M-cluster-derived MSCs examined using a pellet culture system. Chondrogenic differentiation was evaluated by proteoglycan, safranin O, toluidine blue and type II collagen staining. To evaluate the practicality of the procedure for isolating Muse-like cells, we compared chondrogenic potential of M-cluster derived MSCs with expanded cells derived from the clusters formed by unsorted synovial cells.ResultsSynovial membranes contained SSEA-3-positive cells that after isolation exhibited Muse-like characteristics such as forming clusters that expressed NANOG, OCT3/4, and SOX2. In the pellet culture system, cell pellets created from the M-cluster-derived MSCs exhibited an increase in wet weight, which implied an increase in extracellular matrix production, displayed metachromasia with toluidine blue and safranin O staining and were aggrecan-positive and type II collagen-positive by immunostaining. Unsorted synovial cells also formed clusters in methylcellulose culture, and the expanded cell population derived from them exhibited chondrogenic potential. The histological and immunohistochemical appearance of chondrogenic pellet created from unsorted synovial cell-derived cells were comparable with that from M-cluster-derived MSCs.ConclusionsMuse-like cells can be isolated from the human synovial membrane, even from older patients, and therefore may provide a source of multipotent cells for regenerative medicine. In addition, the cluster-forming cell population within synovial cells also has excellent chondrogenic potential. These cells may provide a more practical option for cartilage regeneration.

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“…But personally, the isolated Muse cells may change their characteristics under the severe culture stress. And two published studies are involved in magnetically activated cell sorting (MACS), but their isolation rate were only 77.1% and 71.3% [15,31].…”

Section: Distribution Of Muse Cells In the Bodymentioning

confidence: 99%

“…Mari Dezawa, the first to describe Muse cells, demonstrated that human Muse cells reconstructed neuronal circuity in subacute lacunar stroke SCID mice [15]. In the study, stroke was induced in SCID mice using the stroke model.…”

Section: Muse Cells Treated Strokementioning

confidence: 99%

“…Corresponding author: Xijing He, E-mail: xijing_h@vip.tom.com induction factors in different specific media in vitro, 98% of cells were Osteocalcin+ (osteocyte, mesoderm) [2], 98% were red oil+ (adipocyte, mesoderm) [2], 90% were α-FP+ (hepatocyte, entoderm) [2], 90% were MAP-2+ (Neuron, ectoderm) [2], and 43.1 ± 17.1% were GP100+ (melanocyte, ectoderm) [7,8]. When induced Muse cell cultures were transplanted in vivo, cells differentiated into adipocytes, skeletal muscle cells, myocardial cells, biliary epithelial cells, glomerular cells, glomerular endothelial cells, melanocytes and neurons [8][9][10][11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

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Muse cells and Neurorestoratology

Leng

Kethidi

Chang

et al. 2019

Journal of Neurorestoratology

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Multilineage-differentiating stress-enduring (Muse) cells were discovered in 2010 as a subpopulation of mesenchymal stroma cells (MSCs). Muse cells can self-renew and tolerate severe culturing conditions. These cells can differentiate into three lineage cells spontaneously or in induced medium but do not form teratoma in vitro or in vivo. Central nervous system (CNS) diseases, such as intracerebral hemorrhage (ICH), cerebral infarction, and spinal cord injury are normally disastrous. Despite numerous therapy strategies, CNS diseases are difficult to recover. As a novel kind of pluripotent stem cells, Muse cells have shown great regeneration capacity in many animal models, including acute myocardial infarction, hepatectomy, and acute cerebral ischemia (ACI). After injection into injury sites, Muse cells survived, migrated, and differentiated into functional neurons with synaptic junctions to local neurons and contributed to recovery of function. Furthermore, Muse cell differentiation did not need to be induced pre-transplantation and no tumors were observed post- transplantation. The Muse cell population is promising and may lead to a revolution in regenerative medicine. This review focuses on recent advances regarding the Muse cells therapies in Neurorestoratology and discusses future perspectives in this field.

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Human Muse Cells Reconstruct Neuronal Circuitry in Subacute Lacunar Stroke Model

Cited by 92 publications

References 33 publications

A Novel Type of Stem Cells Double-Positive for SSEA-3 and CD45 in Human Peripheral Blood

A Novel Type of Stem Cells Double-Positive for SSEA-3 and CD45 in Human Peripheral Blood

Multilineage-differentiating stress-enduring (Muse)-like cells exist in synovial tissue

Muse cells and Neurorestoratology

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