Mobilized Muse Cells After Acute Myocardial Infarction Predict Cardiac Function and Remodeling in the Chronic Phase

Abstract

Background: Multilineage differentiating stress-enduring (Muse) cells are SSEA3 + and CD105 + double-positive pluripotent-like stem cells. We aimed to examine the mobilization of Muse cells into peripheral blood after acute myocardial infarction (AMI) and their effects on left ventricular (LV) function and remodeling. Methods and Results:In 79 patients with AMI, 44 patients with coronary artery disease (CAD), and 64 normal subjects (Control), we measured the number of Muse cells in the peripheral blood by fluorescence-activated cell sorting. Muse cells were measured on days 0, 1, 7, 14, and 21 after AMI. Plasma sphingosine-1-phosphate (S1P) levels were measured. Cardiac echocardiography was performed in the acute (within 7 days) and chronic (6 months) phases of AMI. Muse cell number on day 1 was significantly higher in the AMI (276±137 cells/100 μL) than in the CAD (167±89 cells/100 μL) and Control (164±125 cells/100 μL) groups. Muse cell number peaked on day 1, and had gradually decreased on day 21. Muse cell number positively correlated with plasma S1P levels. Patients with a higher increase in the number of Muse cells in the peripheral blood but not those with a lower increase in number of Muse cells in the acute phase showed improved LV function and remodeling in the chronic phase. Conclusions:Endogenous Muse cells were mobilized into the peripheral blood after AMI. The number of Muse cells could be a predictor of prognosis in patients with AMI.

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

“…BM-Muse cells express CD105, a marker for MSCs that is postulated to be involved in cell adhesion and cytoskeleton arrangement, at a higher proportion (∼68%) than PB-SSEA-3(+) cells (∼22%). All of human BM-Muse cells were reported to be negative for HLA-DR 11 , while ∼90% of PB-SSEA-3(+) cells were positive for HLA-DR; (3) PB-SSEA-3(+) cells showed 30∼90 times higher expression of pluripotency markers than BM-Muse cells; (4) PB-SSEA-3(+) cells did not attach to the culture dish and did not actively proliferate under the conventional culture methods used for tissue-derived Muse cells, including that for BM-Muse cells, although various culture conditions should be evaluated in future studies. Low adherence and low proliferation of PB-SSEA-3(+) cells in vitro is considered pertinent to the microenvironment where PB-Muse cells exist; if PB-SSEA-3(+) cells have high adherence and proliferative activity in the PB, they would easily adhere to vessel walls, potentially inhibiting smooth circulation and causing emboli in vessels.…”

“…Muse cells exhibit unique characteristics in vivo. Muse cells express sphingosine-1-phosphate (S1P) receptor 2 (S1PR2) and sense the S1P produced by damaged tissue, which enables them to migrate to and home to the site of tissue damage 11 . Therefore, Muse cells, in both the circulation and tissues, can selectively accumulate at the damaged site.…”

Muse cells and Neurorestoratology

“…Because Muse cells were initially considered to reside in mesenchymal tissues, the percentage of Muse cells in the human bone marrow is assumed to be around 0.01%-0.03% of the mononucleated cell fraction [1]. Muse cells also exist in the peripheral blood at the proportion of 0.01%-0.2% of the mononuclear fraction [27]. But the bone marrow is directly connected to the peripheral blood, so Muse cells in blood should be from the bone marrow.…”

Cardiac Rehabilitation With Dynamic Exercise Increases the Number of Muse Cells in the Peripheral Blood of Patients With Heart Disease

“…The number of SSEA3 + /CD105 + double-positive cells was measured on fluorescence-activated cell sorting (FACS Calibur, Beckton Dickinson, San Jose, CA, USA), as previously reported. 4 The number of Muse cells was expressed as absolute number of Muse cells (/100 μL)=white blood cells (/100 μL)×monocytes (%)×SSEA3 + /CD105 + doublepositive cells (%).…”

“…ultilineage-differentiating stress-enduring (Muse) cells can be isolated as cells double-positive for the pluripotent surface marker SSEA3 and mesenchymal stem cell surface marker CD105 from the bone marrow, peripheral blood, and various connective tissues. [1][2][3][4] We recently reported that endogenous Muse cells are mobilized into the peripheral blood after acute myocardial infarction (AMI); that AMI patients with a higher number of Muse cells in the acute phase had improvement in left ventricular (LV) function and remodeling in the chronic phase; 4 and that Muse cells given i.v. after AMI homed to the damaged myocardium and improved the LV function and remodeling through cardiomyocyte regeneration and paracrine effects in rabbits.…”