Intravenous injection of human multilineage-differentiating stress-enduring cells alleviates mouse severe acute pancreatitis without immunosuppressants

Fukuda, Masahiko; Sakata, Naoaki; Kushida, Yoshihiro; Wakao, Shohei; Unno, Michiaki; Dezawa, Mari

doi:10.1007/s00595-021-02382-7

Cited by 9 publications

(13 citation statements)

References 58 publications

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“…Muse cells are mainly derived from bone marrow mesenchymal stem cells (BM-MSCs), adipocytes and fibroblasts according to the literature. 7 Fibroblasts are easily obtained from the human dermis of discarded prepuce tissues, and their number can be rapidly expanded by in vitro culture. Therefore, dermal fibroblasts were selected as source cells in this study and their identify was confirmed by immunofluorescence staining for vimentin.…”

Section: Discussionmentioning

confidence: 99%

“…Muse cells are widely distributed throughout the body and are not restricted to specific organs or tissues. Muse cells are mainly derived from bone marrow mesenchymal stem cells (BM‐MSCs), adipocytes and fibroblasts according to the literature 7 . Fibroblasts are easily obtained from the human dermis of discarded prepuce tissues, and their number can be rapidly expanded by in vitro culture.…”

Section: Discussionmentioning

confidence: 99%

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Characteristics of multilineage‐differentiating stress‐enduring cell clusters in different culture conditions

Ning,

Cao,

Zhang

et al. 2023

Skin Research and Technology

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ObjectiveTo observe the morphological characteristics of clusters of Muse cells from normal human dermal fibroblasts (NHDFs) under different culture conditions.MethodsMuse cells were sorted by magnetic activated cell sorting (MACS) from NHDFs, and were evaluated by flow cytometry. Muse cells were cultured in suspension and in adherent conditions to obtain Muse cell clusters (M‐clusters), which were further characterized by alkaline phosphatase (AP) staining, immunofluorescence (IF) staining and transmission electron microscopy (TEM). The M‐clusters were further cultured on Lando artificial dermal regeneration matrix (LADRM) for analysis by scanning electron microscopy (SEM) and IF staining of frozen sections.ResultsThe proportion of SSEA3 and CD105 double‐positive cells obtained by MACS was 87.4%. The sorted cells rapidly formed M‐clusters after suspension culture, and showed internal characteristics of stem cells under TEM. After adherent culture, M‐clusters stained positively for AP, SSEA‐3 and OCT‐4. Each M‐cluster on the surface of the LADRM displayed an outer membrane of amorphous materials under SEM. Frozen sections and fluorescence staining of LADRM loaded with M‐clusters showed an uneven fluorescence intensity of SSEA‐3 within the clusters.ConclusionsMuse cells sorted by MACS from NHDFs could generate M‐clusters, which included cells of different stemness and are wrapped in membrane‐like structures.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Characteristics of multilineage‐differentiating stress‐enduring cell clusters in different culture conditions

Ning,

Cao,

Zhang

et al. 2023

Skin Research and Technology

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“…Yang et al [28] reported that the Cxcl12 signalling pathway may function as a bridge between injury and repair in a rat optical nerve injury model. Muse cells have also been reported to be involved in Cxcl12 production [29]. Cxcl12 is also known to function as an anti-inflammatory chemokine [30].…”

Section: Discussionmentioning

confidence: 99%

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

Koyama,

Yamashita,

Kato

et al. 2023

BJU International

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ObjectiveTo 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 MethodsMale Sprague–Dawley rats were randomised into three groups after CN crush injury. Either human‐Muse cells, non‐Muse mesenchymal stem cells (MSCs) (both 1.0 × 105 cells), or vehicle was infused intravenously at 3 h after CN injury without immunosuppressant. Erectile function was assessed by measuring intracavernous pressure (ICP) and arterial pressure (AP) during pelvic nerve electrostimulation 28 days after surgery. At 48 h and 28 days after intravenous infusion of Muse cells, the homing of Muse cells and non‐Muse MSCs was evaluated in the major pelvic ganglion (MPG) after CN injury. In addition, expressions of C‐X‐C motif chemokine ligand (Cxcl12) and glial cell line‐derived neurotrophic factor (Gdnf) in the MPG were examined by real‐time polymerase chain reaction. Statistical analyses and comparisons among groups were performed using one‐way analysis of variance followed by the Tukey test for parametric data and Kruskal–Wallis test followed by the Dunn–Bonferroni test for non‐parametric data.ResultsThe mean (SEM) ICP/AP values at 28 days were 0.51 (0.02) in the Muse cell group, 0.37 (0.03) in the non‐Muse MSC group, and 0.36 (0.04) in the vehicle group, showing a significant positive response in the Muse cell group compared with the non‐Muse and vehicle groups (P = 0.013 and P = 0.010, respectively). In the MPG, Muse cells were observed to be engrafted at 48 h and expressed Schwann cell markers S100 (~46%) and glial fibrillary acidic protein (~24%) at 28 days, while non‐Muse MSCs were basically not engrafted at 48 h. Higher gene expression of Cxcl12 (P = 0.048) and Gdnf (P = 0.040) was found in the MPG of the Muse group than in the vehicle group 48 h after infusion.ConclusionIntravenously engrafted human Muse cells recovered rat erectile function after CN injury in a rat model possibly by upregulating Cxcl12 and Gdnf.

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“…Administration of Muse cells significantly suppressed the infiltration of inflammatory cells such as macrophages and neutrophils and effectively alleviated edema at the site of injury in mouse aortic aneurysm, porcine post-hepatectomy liver failure (PHLF), rat interstitial cystitis, and a severe pancreatitis model ( Hosoyama et al, 2018 ; Iseki et al, 2021 ; Fukase et al, 2022 ; Furuta et al, 2022 ).…”

Section: Muse Cells As Endogenous Pluripotent-like Reparative Stem Ce...mentioning

confidence: 99%

“…In animal models of PHLF, renal injury, pancreatitis, and atopic dermatitis, Muse cells reduced the production of inflammatory cytokines (IL-1B, IL-6, IL-17A, IL-33, TNF) and increased the expression of anti-inflammatory cytokines (IL-10, PGE2, TGF-β, TSG-6) and growth factors (IGF1, VEGFA, VEGFB, VEGFC, VEGFD, EGF, TGFA), contributing to tissue protection and regeneration in the injured organs rather than MSCs ( Uchida et al, 2017b ; Hosoyama et al, 2018 ; Fei et al, 2021 ; Iseki et al, 2021 ; Fukase et al, 2022 ; Furuta et al, 2022 ).…”

Section: Muse Cells As Endogenous Pluripotent-like Reparative Stem Ce...mentioning

confidence: 99%

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

et al. 2022

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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. Circulating Muse cells, either endogenous or administered exogenously, selectively accumulate at the damaged site by sensing sphingosine-1-phosphate (S1P), a key mediator of inflammation, produced by damaged cells and replace apoptotic and damaged cells by spontaneously differentiating into multiple cells types that comprise the tissue and repair the tissue. Thus, intravenous injection is the main route for Muse cell treatment, and surgical operation is not necessary. Furthermore, gene introduction or cytokine induction are not required for generating pluripotent or differentiated states prior to treatment. Notably, allogenic and xenogenic Muse cells escape host immune rejection after intravenous injection and survive in the tissue as functioning cells over 6 and ∼2 months, respectively, without immunosuppressant treatment. Since Muse cells survive in the host tissue for extended periods of time, therefore their anti-inflammatory, anti-fibrotic, and trophic effects are long-lasting. These unique characteristics have led to the administration of Muse cells via intravenous drip in clinical trials for stroke, acute myocardial infarction, epidermolysis bullosa, spinal cord injury, neonatal hypoxic ischemic encephalopathy, amyotrophic lateral sclerosis, and COVID-19 acute respiratory distress syndrome without HLA-matching or immunosuppressive treatment.

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Intravenous injection of human multilineage-differentiating stress-enduring cells alleviates mouse severe acute pancreatitis without immunosuppressants

Cited by 9 publications

References 58 publications

Characteristics of multilineage‐differentiating stress‐enduring cell clusters in different culture conditions

Characteristics of multilineage‐differentiating stress‐enduring cell clusters in different culture conditions

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

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

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