The self-renewal procedures of mesenchymal stem cells in the blood

Abstract

Background: Although mesenchymal stem cells (MSCs) are most commonly used in cell therapy and stem cell research, the mechanism and the locations of their self-renewal are still unknown. Method: Mouse blood was collected, and examined under microscopy. The results were compared with the data of human umbilical cord blood (hUCB) collected 10 years ago. Results: We found that the procedure of self-renewal for the mesenchymal stem cells in mouse blood and hUCB needs at least 5 steps. First, tube-shaped stem cell niches release long segmented materials composed of sand-like particles and semitransparent granules. Second, the sand-like particles and semitransparent granules separate from the segmented materials. Third, each of the individual semitransparent granules releases groups of fusiform-shaped structures that do not stain to H&E. The sizes of the fusiform-shaped structures range from 1 to 100 μm in length in mouse blood, but can be 200 μm in hUCB. Fourth, the large-sized fusiform structures can directly transform into lineage-restricted cellular structures; the medium-sized fusiform structures fuse or engulf each other to form cellular structures. The cellular structures further acquire membranes from the adjacent nucleated cells. Fifth, the nucleolus appears in the new cellular structures before the nucleus. During all the procedures, the adjacent nucleated mesenchymal cells are must needed. Thus, these newly formed cellular structures will further differentiate into nucleated mesenchymal stem cells. Conclusion: Our findings again provide new evidence that, in physiological conditions, mesenchymal stem cell self-renewal needs several steps to complete, which, however, does not occur by mitotic division. The tube-shaped structures are the niches of the stem cells.

Development of membrane-like pre-stem cells after released from tube-shaped niches

“…Haematoxylin and eosin (H&E) staining was performed to further examine the colour differences of these tube-shaped structures. Besides the light-purple colour, copper colour, and dark blue colours that were described in our previous publications 19, 22 , we identified more colours stains on these tube-shaped structures. Figure 2 reveals several tube-shaped structures sorted by the H&E staining: dark-grey (Fig.…”

“…Unlike the tube-shaped niches, each restricted inclusion showed not only a colour difference but also fundamental morphological differences, such as the thin filaments 19 , bud shaped 19 , erythrocyte sacs 21 , dark fragments 22 , plus the currently described red bamboo-like and geometric membrane-shaped. Thus, each lineage was sorted out by its unique colour and distinct morphology.…”

“…In our previous reports, we found that pre-stem tissues originate form tube-shaped structures. These pre-stem tissues have distinct morphological differences 19 , such as thin filaments-released spore-like, or dark fragments-released fusiform-shape 22 . Because each of these structures produces and releases only one distinct spore-like cell type, or progenitors, we believe that the lineage of these progenitors has been predetermined in their tube-shaped structure, or niche.…”

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“…Haematoxylin and Eosin (H&E) staining was performed to further examine the colour differences of these tube-shaped structures. Besides the light-purple colour, copper colour, and dark blue colours that were described in our previous publications [19,20], we identified more colours stains on these tube-shaped structures. Figure 2 reveals several tube-shaped structures sorted by the H&E staining: dark-grey (Figure 2A), dark blue (Figure 2B), no staining (Figure 2C), and red colour (Figure 2D).…”

“…In our previous reports, we found that pre-stem tissues originate form tube-shaped structures. These pre-stem tissues have distinct morphological differences [19], such as thin filaments-released sporelike, or dark fragments-released fusiform-shape [20]. Because each of these structures produces and releases only one distinct spore-like cell type, or progenitors, we believe that the lineage of these progenitors has been predetermined in their tube-shaped structure, or niche.…”