[In vivo migration of mesenchymal stem cells].

Mesenchymal stem cells (MSC) have the capacities of low immunogenicity, multiple differentiation, hematopoietic supporting and immunoregulation. And due to their relative ease of availability and ex vivo expansion, the applications of MSC in the prevention and treatment of clinical disease have been rapidly expanded in the recent years. However, increasing investigations indicate that intravenously infused MSC widely distribute to various organs of the recipients. The two intended clinical goals of adoptive cellular therapy reached to the greatest efficiency. Therefore, the ideal candidate cells showed to have the capacity of site-specific relocation in vivo. In this review, the distribution characteristics of infused MSC and the recent research advances on the strategies to enhance targeted migration of MSCs are summarized.

Cilostazol protects the heart against ischaemia reperfusion injury in a rabbit model of myocardial infarction: focus on adenosine, nitric oxide and mitochondrial ATP-sensitive potassium channels.

1. The present study examined whether or not cilostazol reduces the myocardial infarct size, and investigated its mechanism in a rabbit model of myocardial infarction. 2. Japanese white rabbits underwent 30 min of coronary occlusion, followed by 48 h of reperfusion. Cilostazol (1 and 5 mg/kg) or vehicle was given intravenously 5 min before ischaemia. 8-p-sulfophenyl theophylline (8SPT; an adenosine receptor blocker, 7.5 mg/kg), Nω-nitro-L-arginine methylester (l-NAME; an NOS inhibitor, 10 mg/kg) or 5-hydroxydecanoic acid sodium salt (5-HD; a mitochondrial ATP-sensitive potassium (KATP) channel blocker, 5 mg/kg) was given intravenously 5 min before cilostazol injection. Infarct size was determined as a percentage of the risk area. 3. The myocardial interstitial levels of adenosine and nitrogen oxide (NOx) during ischaemia and reperfusion, and the intensity of myocardial dihydroethidium staining were determined. 4. Infarct size was significantly reduced in the cilostazol 1 mg/kg (38.4% (2.9%)) and cilostazol 5 mg/kg (30.7% (4.7%)) groups compared with that in the control group (46.5% (4.2%)). The infarct size-reducing effect of cilostazol was completely abolished by 8SPT (46.6% (3.5%)), L-NAME (49.0% (5.5%)), or 5HD (48.5% (5.1%)). 8SPT, L-NAME or 5HD alone did not affect the infarct size. Cilostazol treatment significantly increased myocardial levels of adenosine and NOx during ischaemia, and attenuated the intensity of dihydroethidium staining during reperfusion. 5. These findings show that cilostazol reduces the myocardial infarct size by increasing adenosine and NOx levels, attenuating superoxide production and opening the mitochondrial KATP channels. Cilostazol might provide a new strategy for the treatment of coronary heart disease.

Graft expression of p38 and tumor necrosis factor-alpha in heart transplantation in rats.

OBJECTIVES: To investigate the expression of p38 mitogen-activated protein kinase and its relationship with myocardial apoptosis and tumor necrosis factor-alpha during acute cardiac allograft rejection and to study the effects of tacrolimus on the expression of the kinase. METHODS: Rats were divided into 3 groups: isograft (Lewis heart to Lewis rat; control group), allograft (Brown Norway heart to Lewis rat), and tacrolimus-treated allograft (Brown Norway heart to tacrolimus-treated Lewis rat). Grafts were collected 1, 3, 5, and 7 days after transplantation for determination of histopathological features, apoptosis of cardiac cells (by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick labeling), number of cells positive for both p38 and CD8 (by laser scanning confocal imaging), and expression of the kinase (by Western immunoblotting) and tumor necrosis factor-alpha (by reverse-transcriptase polymerase chain reaction). RESULTS: Compared with isografts from the control group, grafts from the untreated allograft group had significantly more apoptotic cells, greater expression of tumor necrosis factor-alpha and p38 mitogen-activated protein kinase, and more CD8-p38 double-positive cells at 5 and 7 days (P < .05). The increases were prevented by treatment with tacrolimus. CONCLUSIONS: The findings that the number of apoptotic cells, the number of CD8-p38 double-positive cells, the expression of tumor necrosis factor-alpha and p38 mitogen-activated protein kinase all increased during the same period in the allografts in nonimmunosuppressed recipients suggests that intragraft expression of p38 would be associated with the rejection in acute cardiac allograft rejection. Tacrolimus may alleviate rejection partly by inhibiting p38 mitogen-activated protein kinase.