Abstract
Background: Bone marrow (BM)-derived stem cells with their various functions and characteristics have become a well-recognized source for the cell-based therapies. However, knowledge on their therapeutic potential and the shortage for a cross-link between distinct BM-derived stem cells, primed after the onset of myocardial infarction (MI), seems to be still rudimentary. Therefore, the post-examination of the therapeutic characteristics of such primed hematopoietic CD133+ and mesenchymal CD271+ stem cells was the object of the present study. Methods and Results: The effects of respective CD133+ and CD271+ mononuclear cells alone as well as in the co-culture model have been explored with focus on their angiogenic potential. The phenotypic analysis revealed a small percentage of isolated cells expressing both surface markers. Moreover, target stem cells isolated with our standardized immunomagnetic isolation procedure did not show any negative alterations following BM storage in regard to cell numbers and/or quality. In vitro network formation relied predominantly on CD271+ stem cells when compared with single CD133+ culture. Interestingly, CD133+ cells contributed in the tube formation, only if they were cultivated in combination with CD271+ cells. Additional to the in vitro examination, therapeutic effects of the primed stem cells were investigated 48 h post MI in a murine model. Hence, we have found a lower expression of transforming growth factor βeta 3 (TGFβ3) as well as an increase of the proangiogenic factors after CD133+ cell treatment in contrast to CD271+ cell treatment. On the other hand, the CD271+ cell therapy led to a lower expression of the inflammatory cytokines. Conclusion: The interactions between CD271+ and CD133+ subpopulations the extent to which the combination may enhance cardiac regeneration has still not been investigated so far. We expect that the multiple characteristics and various regenerative effects of CD271+ cells alone as well as in combination with CD133+ will result in an improved therapeutic impact on ischemic heart disease.
Highlights
In order to cover up the deficit of regenerative potential, new treatment approaches for cardiac diseases are needed
We have explored the effects of CD271+ cells alone as well as in combination with CD133+ with the main focus on their angiogenic potential
In order to optimize the procedure of cell isolation it had to be determined which impact the dual isolation strategy has on the cell product quality
Summary
In order to cover up the deficit of regenerative potential, new treatment approaches for cardiac diseases are needed. Cells 2020, 9, 78 cell subtypes, various other properties are of interest as well This includes cells that interfere with pathological immune mechanisms as well as cellular mediators and chemokines that cause migration and homing processes. As the CD133+ stem cell therapies and other approaches with hematopoietic cells provide promising results, research has to examine more cell types in order to achieve additional effects and to further improve the therapeutic measures. Bone marrow (BM)-derived stem cells with their various functions and characteristics have become a well-recognized source for the cell-based therapies. Knowledge on their therapeutic potential and the shortage for a cross-link between distinct BM-derived stem cells, primed after the onset of myocardial infarction (MI), seems to be still rudimentary. CD133+ cells contributed in the tube formation, only if they were cultivated in combination with
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