The Influence Of3D Culture On Mesenchymal Stem Cell Trafficking And Therapeutic Effect On Ischemic Stroke

Mesenchymal stem cells (MSCs) were discovered from bone marrow years agoand we can also find MSCs in many organs in our body. It is widely proved to havegood curative effect on many diseases which indicate its good future of clinicalapplication. But MSCs size become bigger after adhensive culture in vitro which resultin attenuating its trafficking ability in microvascular system, capillary occlusion all thatwill lead to less MSCs migrate to target tissue. This disadvantage is reduce its safetyand efficiency of clinical application.We find the change of morphology and gene expression of MSCs after it isadhensive cultured for several passages. In this study, we try to establish threedimensional cultured MSCs (3D MSCs) to converse the2D MSCs back to goodcondition, and analysis whether these3D MSCs have a better curative effect on strokemodel.Our data show that2D MSCs grow into bigger volume, with its diameter fromaverage21μm to26μm, however, its average diameter become smaller into average13μm after60hours3D culture. Our3D group rats significantly recovered better than2D group rats. Firstly, the cell number of engrafted3D MSCs is50%more than2DMSCs, the average deceased ischemic area in3D group rats is12%more2D group.3Dgroup rats also recover better on their neurological function. Some paracrine secreted by3D MSCs is significant higher than2D MSCs.Finally, we compare the advantage and side effect of MSCs during intra-arterialcell transplantation. High mortality always happened in rats which was injected with2DMSCs. And many rats will suffer blindness on their left eyes in2D groups. I divided2DMSCs into two group of cells with different sizes, and design a video system to provethat cell size determinate the safety of intra-arterial cell transplantation.In a word, we find3D MSCs have strong differentiation ability, higher VEGF andBDNF paracrine, more engraftment than2D MSCs, and we successfully prove thatMSCs size determinate the safety of intra-arterial cell transplantation.3D MSCsbecome smaller after3D culture system, so3D MSCs bring a new hope to MSCs clinical application, and regarding to our new finding, other researchers will have aactually standard that they can not apply big size stem cell into therapy by throughintra-arterial transplantation.