Duchenne muscular dystrophy (DMD) is a common X-linked disease characterized by widespread muscle damage that invariably leads to paralysis and death. There is currently no therapy for this disease. This study was purposed to investigate the feasibility to use adult adipose-derived mesenchymal stem cells (AD-MSCs) in the therapy of DMD. The Flk-1(+) MSCs were isolated from adipose tissue of adult GFP mice; the phenotype and cell cycle of MSCs were analyzed by flow cytometry; the AD-MSCs were directionally differentiated by myoblast and endotheliablast induction system in vitro and were identified by immumofluorecence staining and RT-PCR; the AD-MSCs were transplanted into CTX-injured mice model or mdx mice (DMD animal model) through tail vein; the distribution and differentiation of AD-MSCs were detected by immunofluorescence staining and RT-PCR respectively, and statistic analysis was performed. The results showed that the Flk-1(+) AD-MSCs could be induced to differentiate into myoblasts and endothelial cells in vitro. After transplanted into CTX-injured mice model or mdx mice, GFP-positive cells could be detected in damaged muscle, and these donor-derived cells were also positive for MHC, vWF, or Pax7. Flk-1(+) AD-MSC transplantation also partly reconstituted the expression of dystrophin, and reduced the percentage of centronucleated myofibers in mdx mice. It is concluded that Flk-1(+) AD-MSCs represent a possible tool for future cell therapy applications in DMD disease, as they can be delivered through the circulation for their potential of muscle homing. And Flk-1(+) AD-MSCs also show the ability to contribute to muscle repair, improvement of blood supply and long term reconstitution of dystrophy muscle.
Adipose Tissue ; cytology ; Animals ; Cell Differentiation ; Cells, Cultured ; Dystrophin ; biosynthesis ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; cytology ; Mice ; Mice, Inbred C57BL ; Mice, Inbred mdx ; Mice, Transgenic ; Muscle Cells ; cytology ; Muscular Dystrophy, Duchenne ; pathology ; therapy ; Myoblasts ; cytology

BACKGROUNDThe infarct size determines the long-term prognosis of patients with acute myocardial infarction (AMI). There is a growing interest in repairing scar area by transplanting bone marrow stem cells. However, effectiveness of intracoronary injection of bone marrow mesenchymal stem cells (BMSCs) in patients with AMI still remains unclear.

METHODSSixty-nine patients with AMI after percutaneous coronary intervention (PCI) were randomly divided into intracoronary injection of BMSCs (n = 34) and saline (control group, n = 35) groups. Serial single positron emission computer tomography (SPECT), cardiac echo and cardiac electromechanical mapping were done at the designed time intervals until six months after transplantation of BMSCs or injection of saline.

RESULTSThe proportion with functional defect decreased significantly in the BMSCs patients after three months [(13 +/- 5)%] compared with that pre-transplantation [(32 +/- 11)%] and the control group [(28 +/- 10)%] at three month follow-up (P < 0.05, respectively). Wall movement velocity over the infracted region increased significantly in the BMSCs group [(4.2 +/- 2.5) cm/s vs (2.2 +/- 1.3) cm/s, P < 0.05], but not in the control group [(2.2 +/- 1.5) cm/s vs (2.7 +/- 1.7) cm/s, P > 0.05]. Left ventricular ejection fraction (LVEF) three months after transplantation in BMSCs group increased significantly compared with that pre-implantation and with that of the control group at three months post-injection [(67 +/- 11)% vs (49 +/- 9)% and (53 +/- 8)%, P < 0.05 respectively]. SPECT scan results showed that perfusion defect was improved significantly in BMSCs group at three-month follow-up compared with that in the control group [(134 +/- 66) cm(2) vs (185 +/- 87) cm(2), P < 0.01]. At the same time, left ventricular end-diastolic volume [(136 +/- 31) ml vs (162 +/- 27) ml, P < 0.05] and end-systolic volume [(63 +/- 20) ml vs (88 +/- 19) ml, P < 0.05] decreased synchronously. The ratio of end-systolic pressure to end-systolic volume [Psyst/ESV, (2.84 +/- 1.30) mmHg/ml vs (1.72 +/- 1.23) mmHg/ml, P < 0.05] increased significantly. Cardiac electromechanical mapping demonstrated significant improvement at three months after implantation of BMSCs compared with that pre-injection in both cardiac mechanical capability as left line local shorting [LLS, (11.29 +/- 1.64)% vs (7.32 +/- 1.86)%, P < 0.05] and electrical property as left ventricular endocardial unipolar voltage [UV, (10.38 +/- 1.12) mV vs (7.61 +/- 1.09) mV, P < 0.01]; perfusion defect decreased from (36.2 +/- 6.2)% to (20.3 +/- 5.31)% (P < 0.01). Twenty-four-hour electrocardiographic monitoring demonstrated no arrhythmias occurred at three-months follow-up.

CONCLUSIONSThe transplantation of BMSCs might improve the cardiac function and it is safe and feasible with no deaths or malignant arrhythmias.

Adult ; Aged ; Bone Marrow Cells ; cytology ; Female ; Humans ; Male ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; cytology ; Middle Aged ; Myocardial Infarction ; therapy ; Tomography, Emission-Computed, Single-Photon ; Transplantation, Autologous