# Advanced Microbubbles as a Multifunctional Platform Combining Imaging and Therapy
## 2 Advanced Microbubbles for Imaging and Therapy
### Stem Cell Transplantation  
Although stem cell transplantation has been applied in treatments of various diseases, its clinical application is restricted by the influence of survival rate and targeting of stem cells. To this end, US + MBs cannot only mediate the gene transfection, but also facilitate targeted delivery of transplanted cells to improve the performance of stem cell transplantation. [PERSON] transplanted DAPI-labeled MSCs to the myocardial infarction models by means of UTMD, and found that the expression of various cytokines in UTMD-treated animals was much higher than that observed in non-treated controls. They concluded that UTMD changes the myocardial microenvironment and promotes the homing of MSCs to the ischemic myocardium [97]. [PERSON] established the targeted delivery of MSCs into the myocardium by using diagnostic US irradiating lipid-coated MB destruction along with bone-marrow-derived MSC infusion. The cardiac function was markedly improved and the number of capillaries was increased, whereas, the area of cardiac fibrosis was significantly decreased with US + Microbubble + MSC treatment [98]. [PERSON] and his fellows transferred pcDNA3.1-hVEGF165 into MSCs by UTMD, and observed the effect of the protein expression. It showed that the VEGF165 protein expression increased at 24 h and reached the maximum level at 48 h. Compared with the control, protein expression of the UTMD group was significantly increased. It also found that VEGF165 protein level varied to different UTMD conditions. A significant protein expression was yielded by UTMD-mediated transfection of MSCs with a mechanic index of 0.6 for 90 s [99].  
Bone marrow stromal cell (BMSC) transplantation proves successful in treating kidney diseases. [PERSON] et al. applied UTMD to enhance CXCR-4 transfection efficiency to improve BMSC homing to AKI kidneys, which showed the migration ability of CXCR-4-modified BMSCs was 9-fold higher than controls without UTMD [100]. [PERSON] developed SDF-1-loaded MBs (MBSDF-1) via covalent conjugation to improve MSC homing to diabetic nephropathy (DN) kidneys. SDF-1 was successfully released in the targeted kidneys in the in vivo study. The homing efficacy of MSCs to DN kidneys after the targeted release of SDF-1 was remarkably ameliorated at 24 h [101]. [PERSON] also performed UTMD to increase the renorprotective effect of kidney-targeted transplantation of bone-marrow-derived mesenchymal stem cells (BM-MSCs) in DN rats. MSCs were injected in combination with UTMD to DN rats at four weeks after diabetes onset. The results demonstrated MSC transplantation could decrease blood glucose concentrations and attenuate pancreatic islets/\(\beta\) cells damage. The permeability of renal interstitial capillaries and VCAM-1 expression increased after UTMD employment, which enhanced homing and retention of MSCs to kidneys. MSC transplantation associated with UTMD prevented renal damages and decreased albumin excretion rate (AER) values. It was concluded that UTMD non-invasively increased the homing of MSCs to kidneys and promoted renal repair in DN rats [102].