Bone marrow-derived pluripotent very small embryonic-like stem cells (VSELs) are mobilized after acute myocardial infarction

Abstract

The adult bone marrow (BM) harbors Sca-1+/Lin−/CD45− pluripotent very small embryonic-like stem cells (VSELs), which can differentiate in vitro into several lineages, including cardiac and vascular lineages. Since mobilization of stem/progenitors from the BM is a prerequisite for their participation in organ repair, we investigated whether VSELs are mobilized into the peripheral blood (PB) after acute myocardial infarction (MI). Wild-type mice (C57/BL6 strain, 6-or 15-wk-old) underwent a 30-min coronary occlusion followed by reperfusion (groups III-V, VIII-X, n=6-12/ group) or a 1-h open-chest state (sham controls, groups II and VII, n=8-12/group); mice were sacrificed 24 h, 48 h, or 7 days later and PB samples were harvested. Controls (groups I and VI, n=6/ group) were sacrificed without any intervention. By flow cytometry, VSELs were barely detectable in PB under baseline conditions but their levels increased significantly at 48 h after MI, both in younger (6-wk-old) and older (15-wk-old) mice (3.33±0.37 and 7.10±0.89 cells/μl of blood, respectively). At 48 h after MI, qRT-PCR analysis revealed significantly increased levels of mRNA of markers of pluripotency (Oct-4, Nanog, Rex-1, Rif1, and Dppa1) in PB cells of 6-wk-old (but not 15-wk-old) infarcted mice compared with either controls or sham controls. Confocal microscopy and ImageStream analysis confirmed that mobilized VSELs expressed Oct-4 protein, while Sca-1+/Lin −/CD45+ hematopoietic stem cells did not. This is the first demonstration that Oct-4+ pluripotent stem cells (VSELs) are mobilized from the BM into the PB after acute MI. This phenomenon may have pathophysiological and therapeutic implications for repair of infarcted myocardium.

Erythropoietin Modulates the Structure of Bone Morphogenetic Protein 2–Engineered Cranial Bone

“…32 Interestingly, this adult stem cell can be mobilized and recruited to injured tissues. 36,37 These observations, coupled with previous reports, suggest that Epo increases the stem cell pool in bone marrow and contributes to local bone regeneration induced by BMPs. 38,39 In line with the increase in hematopoietic-related progenitor cells, Epo treatment increased the number of osteoclasts that are derived from the hematopoietic lineage (Fig.…”

Pluripotent Stem Cells in Bone Marrow and Cord Blood

“…Their presence amongst the MSCs in the Wharton's jelly is in agreement with observations made by other groups that MSCs contain a sub-population of more primitive stem cells [52] or even as postulated by Taichman and group [53] that VSELs are precursors of MSCs. Various studies have also reported that VSELs are mobilized into peripheral blood in response to injury/ stress in animal models [27,[54][55][56] as well as in humans [28][29][30]57] -thus suggesting a role in regeneration and homeostasis.…”

Pluripotent Stem Cells: Origin, Maintenance and Induction

“…During this research, the mobilization of these cells from BM to PB after liver and skeletal muscle damage was confirmed. Mobilization of VSELs after acute myocardial infarction has been proved in mice and human beings with a maximum peak at 48 and 24 h respectively [77,78]. Since injured tissue upregulates stromal derived factor-1 (SDF-1) expression, they are thought to migrate towards damaged organs in a SDF-1 chemotactic fashion.…”