Stem cells are primitive self renewing undifferentiated cell that can be differentiated into various types of specialized cells like nerve cell, skin cells, muscle cells, intestinal tissue, and blood cells. Stem cells live in bone marrow where they divide to make new blood cells and produces peripheral stem cells in circulation. Under proper environment and in presence of signaling molecules stem cells begin to develop into specialized tissues and organs. These unique characteristics make them very promising entities for regeneration of damaged tissue. Day by day increase in incidence of heart diseases including left ventricular dysfunction, ischemic heart disease (IHD), congestive heart failure (CHF) are the major cause of morbidity and mortality. However infracted tissue cannot regenerate into healthy tissue. Heart transplantation is only the treatment for such patient. Due to limitation of availability of donor for organ transplantation, a focus is made for alternative and effective therapy to treat such condition. In this review we have discussed the new advances in stem cells such as use of cord stem cells and iPSC technology in cardiac repair. Future approach of CB cells was found to be used in tissue repair which is specifically observed for improvement of left ventricular function and myocardial infarction. Here we have also focused on how iPSC technology is used for regeneration of cardiomyocytes and intiating neovascularization in myocardial infarction and also for study of pathophysiology of various degenerative diseases and genetic disease in research field.
Blood Cells ; Bone Marrow ; Fetal Blood* ; Heart Diseases ; Heart Failure ; Heart Transplantation ; Humans ; Incidence ; Mortality ; Muscle Cells ; Myocardial Infarction ; Myocardial Ischemia ; Myocytes, Cardiac ; Neurons ; Organ Transplantation ; Pluripotent Stem Cells* ; Regeneration ; Skin ; Stem Cells* ; Tissue Donors ; Transplants ; Ventricular Dysfunction, Left ; Ventricular Function, Left

OBJECTIVETo investigate whether heart tissue-derived extracellular matrix (ECM) promotes the differentiation of cardiosphere-derived cells (CDCs) implanted in rat infracted myocardium to improve the cardiac structure and function.

METHODSRat CDCs were cultured by cardiac explant methods, and ECM was prepared by decelluariztion method. In a Wistar rat model of acute myocardial infarction established by ligating the left anterior descending branch, IMDM solution, ECM suspension, 10CDCs in IMDM solution, or 10CDCs in ECM suspension were injected into the infracted rat myocardium (6 rats in each group). The cardiac function of the rats was evaluated by cardiac ultrasonography, and the percentage of positive heart fibrosis area after infarction was determined with Masson staining. The differentiation of implanted CDCs in the infarcted myocardium was detected using immunofluorescence assay for the markers of cardiac muscle cells (α-SA), vascular endothelial cells (vWF) and smooth muscle cells (α-SMA).

RESULTSThree weeks after acute myocardial infarction, the rats with injection of CDCs in ECM showed the highest left ventricular ejection fraction (LVEF) and percentage of fraction shortening with the lowest percentage of positive heart fibrosis area; implantation of CDCs with ECM resulted in significantly higher rates of CDC differentiation into cardiac muscle cells, vascular endothelial cells and smooth muscle cell (P<0.05).

CONCLUSIONHeart-tissue derived ECM significantly promotes the differentiation of CDCs implanted in the infracted myocardium into cardiac muscle cells, vascular endothelial cells and smooth muscle cells to improve the cardiac structure and cardiac functions in rats.

Animals ; Cell Differentiation ; Cells, Cultured ; Disease Models, Animal ; Endothelial Cells ; cytology ; Extracellular Matrix ; transplantation ; Myocardial Infarction ; therapy ; Myocardium ; Myocytes, Cardiac ; transplantation ; Myocytes, Smooth Muscle ; cytology ; Rats ; Rats, Wistar

In developed countries, in which people have nutrient-rich diets, convenient environments, and access to numerous medications, the disease paradigm has changed. Nowadays, heart failure is one of the major causes of death. In spite of this, the therapeutic efficacies of medications are generally unsatisfactory. Although whole heart transplantation is ideal for younger patients with heart failure, many patients are deemed to be unsuitable for this type of surgery due to complications and/or age. The need for therapeutic alternatives to heart transplantation is great. Regenerative therapy is a strong option. For this purpose, several cell sources have been investigated, including intrinsic adult stem or progenitor cells and extrinsic pluripotent stem cells. Most intrinsic stem cells seem to contribute to a regenerative environment via paracrine factors and/or angiogenesis, whereas extrinsic pluripotent stem cells are unlimited sources of cardiomyocytes. In this review, we summarize the various strategies for using regenerative cardiomyocytes including our recent progressions: non-genetic approaches for the purification of cardiomyocytes and efficient transplantation. We expect that use of intrinsic and extrinsic stem cells in combination will enhance therapeutic effectiveness.
Animals ; Embryonic Stem Cells/cytology ; Humans ; Myocardium/*cytology/*metabolism ; Myocytes, Cardiac/*cytology ; *Regeneration ; Stem Cell Transplantation ; Tissue Engineering

Animals ; Benzofurans ; pharmacology ; therapeutic use ; Bone Marrow Cells ; cytology ; Cell Differentiation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Humans ; Mesenchymal Stem Cell Transplantation ; methods ; Mesenchymal Stromal Cells ; cytology ; Myocardial Infarction ; drug therapy ; therapy ; Myocytes, Cardiac ; cytology ; Phytotherapy ; Salvia miltiorrhiza ; chemistry

The purpose of this study was to observe whether human peripheral dervied monouncleas cells (hMNCs) could participate in the regeneration process of the ischemic hearts in the way of differentiating into cardiomyocytes, vascular endothelial cells and smooth muscle cells. hMNCs were transplanted into the bodies of the mice with myocardial infarction through the tail vein injection. Hearts were harvested 2-12 weeks after injection then sliced up into frozen sections of 5 micron thickness. Double immunofluorescence staining was used to test the differentiation of the grafted cells into cardiomyocytes, smooth muscle cells and vascular endothelial cells which revealed that cells expressing both HLA and TNT, HLA and alpha-SMA, HLA and vWF existed in the hearts of the mice. According to the study, it is probable that hMNCs could participate in the regeneration process of the infarcted hearts in the way of differentiation.
Animals ; Cell Differentiation ; physiology ; Humans ; Leukocytes, Mononuclear ; transplantation ; Mice ; Mice, Nude ; Myocardial Infarction ; pathology ; therapy ; Myocytes, Cardiac ; cytology ; Transplantation, Heterologous

BACKGROUNDMesenchymal stem cells (MSCs) transplantation is of therapeutic potential after ischemic injury in both experimental and clinical studies. Clinically, elderly patients are more vulnerable to acute myocardial infarction (AMI). But little is known about the characteristics of young donor-derived MSCs transplanted to old patients with AMI. The present study was designed to investigate the effect of transplanted MSCs from rats of different ages on the improvement of heart function after AMI.

METHODSMSCs from Sprague-Dawley (SD) rats were isolated and cultured in vitro. The apoptosis characteristics of MSCs were observed under conditions of ischemia and anoxia. SD rats underwent MI received intramyocardial injection of MSCs from young donor rats (n = 8), old donor rats (n = 8), respectively. AMI control group received equal volume physiological saline. Immunofluorescence was used to observe the differentiation of the grafted cells into cardiomyocytes. Four weeks after cell transplantation, reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry for vascular endothelial growth factor (VEGF), VIII-factor immunohistochemistry for vessel density, TUNEL, caspase-3 for cardiomyocyte apoptosis, echocardiography and hemodynamic detection for heart function were performed.

RESULTSThe apoptosis rate of the old donor-derived MSCs group was significantly higher than that of the young donor-derived MSCs group under conditions of ischemia and anoxia (P < 0.05). Engrafted MSCs survived, proliferated and differentiated into myocardium-like cells. VEGF gene expression and capillary density in the old donor-derived group were lower than those in the young donor-derived group but higher than those in the control group (P < 0.05). The transplantation of old donor-derived MSCs attenuated apoptosis of cardiomyocytes in the peri-infarct region compared with the control group and the effect was elevated in young donor-derived MSCs (P < 0.05). The heart functions (left ventricle ejection fraction (LVEF), left ventricle fractional shortening (LVFS)) were improved more significantly in the old donor-derived MSCs group than in the control group and the heart function in the young donor-derived MSCs group further improved (P < 0.05).

CONCLUSIONSYoung donor-derived MSCs can improve heart function significantly through angiogenesis and decreasing cardiomyocyte apoptosis when transplanted to the infarcted area.

Age Factors ; Animals ; Apoptosis ; Caspase 3 ; metabolism ; Cells, Cultured ; Flow Cytometry ; Immunohistochemistry ; In Situ Nick-End Labeling ; Male ; Mesenchymal Stem Cell Transplantation ; methods ; Mesenchymal Stromal Cells ; cytology ; Myocardial Infarction ; physiopathology ; surgery ; Myocytes, Cardiac ; cytology ; enzymology ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

OBJECTIVESTo investigate the effect of HOE642 on cardiac myocyte apoptosis of the heterotopic heart transplantation of rat non heart-beating donors.

METHODSTotally 112 male Sprague-Dawley rats were randomly divided into 7 groups (n=16 in each group) C, the control group (normal hearts); S10, S30, and S45 (groups of transplanted hearts after 10, 30, and 45 minutes of asystole); and SH10, SH30, and SH45 (groups of transplanted hearts after 10, 30, and 45 minutes of asystole and infused with HOE642). After rata in the experimental groups were killed by warm ischemia the donators of the S10, S30 and S45 groups were infused with 5TH-1 for 30 minutes, and the dead rats in group SH10, SH30, and SH4 were infused with STH-1 and HOE642 (20 micromol/L) for 30 minutes. Heterotopic heart transplantation were processed by the method of neck Cuff. The heart specimens of S10, SH10, S30, and SH30 groups were taken after 48 hours of transplantation, and the heart specimens of S45 and SH45 groups were taken immediately after transplantation. Then apoptotic myocytes were detected with terminal deoxynucleotide transferase-mediated deoxyuridine-biotin nick end labeling method and the expressions of Bcl-2, Bax, and Caspase-3 proteins were detected by immunohistochemistry.

RESULTSThe rats were discerned death when cardiac electric wave vanished after 9-11 minutes of bloodletting by transsection of abdominal aorta. The number of positive cardiac muscle cells in S10 and S30 groups were significantly larger than those in group SH10 and SH30 (P < 0.05). The levels of Bcl-2 protein expression in S10 and S30 groups were significantly lower than those in SH10 and SH30 groups (P < 0.05). The levels of Bax and Caspase-3 protein expression were significantly higher than those in SH10 and SH30 groups (P < 0.05).

CONCLUSIONSThe rat model of a heterotopic heart transplantation on the cervical part is a convenient animal model for cardiac muscle protection. HOE642 can suppress rat cardiac muscle cells apoptosis (within 30 min) after death caused by warm ischemia.

Animals ; Anti-Arrhythmia Agents ; pharmacology ; Apoptosis ; drug effects ; Gene Expression ; drug effects ; Guanidines ; pharmacology ; Heart ; physiopathology ; Heart Transplantation ; Male ; Myocardial Contraction ; drug effects ; Myocytes, Cardiac ; cytology ; drug effects ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sulfones ; pharmacology

The effects of cardiomyocyte grafting on left ventricular (LV) remodeling and function in rats with chronic myocardial infarction were evaluated using high-frequency ultrasound. Chronic myocardial infarction was induced in 50 Wister rats by ligating the left anterior descending artery. They were randomized into two groups: a trial group that received neonatal rat cardiomyocyte transplantation (n=25) and a control group which were given intramyocardial injection of culture medium (n=25). The left ventricular (LV) geometry and function were evaluated by high-frequency ultrasound before and 4 weeks after the cell transplantation. After the final evaluation, all rats were sacrificed for histological study. The results showed that 4 weeks after the cell transplantation, as compared with the control group, the LV end-systolic dimension, end-diastolic dimension, end-systolic volume and end-diastolic volume were significantly decreased and the LV anterior wall end-diastolic thickness, LV ejection fraction and fractional shortening were significantly increased in the trial group (P<0.01). Histological study showed that transplanted neonatal rat cardiomyocytes were found in all host hearts and identified by Brdu staining. It was suggested that transplantation of neonatal rat cardiomyocytes can reverse cardiac remodeling and improve heart function in chronic myocardial infarction rats. High-frequency ultrasound can be used as a reliable technique for the non-invasive evaluation of the effect of cardiomyocyte transplantation.
Animals, Newborn ; Echocardiography/*methods ; Myocardial Infarction/physiopathology ; Myocardial Infarction/*therapy ; Myocardial Infarction/ultrasonography ; Myocytes, Cardiac/*transplantation ; Random Allocation ; Rats, Wistar ; Ventricular Function, Left/*physiology ; Ventricular Remodeling

OBJECTIVETo evaluate the therapeutic potential of marrow-derived cardiac stem cell (MCSC) transplantation after myocardial infarction (MI) in rats.

METHODSMCSC were selected from the marrow mesenchymal stem cell (MMSC) of male SD rats by single-cell cloning culture. MI was induced by left anterior descending artery ligating in female SD rats. Equal volume PBS, MMSC and MCSC were transplanted at the border zone of the infarct one week after MI. Cardiac function was assessed by echocardiography at four weeks after cell transplantation. The hearts were removed and morphological changes of scar tissue were examined with HE staining and Masson trichrome staining, VEGFR-1(+) capillary vessels were labeled with immunohistochemical staining. Scar area and vessel density were measured by image analyzer. MCSC containing Y chromosome were examined using in situ fluorescent hybridization, and cardiomyocyte cTnT expression was also analyzed.

RESULTSCardiac transcription factor Nkx2.5 was expressed at low level in c-kit(+) MCSC. Four weeks after cell transplantation, left ventricular fractional shortening and ejection fraction were significantly higher while scar area was significantly lower in MCSC group compared to MMSC group and control group. cTnT was expressed in cells containing Y chromosome and these cells were connected with myocardium of recipient rats in the rats transplanted with MCSC. Vessel density around the infarcted tissue in MCSC group was similar as that in MMSC group and significantly higher than that in control group.

CONCLUSIONMSCS could effectually differentiate into functional cardiomyocytes at the border zone of the infarct, and MCSC transplantation post MI significantly improved cardiac functions and promoted angiogenesis.

Animals ; Bone Marrow Cells ; cytology ; Cell Differentiation ; Disease Models, Animal ; Female ; Myocardial Infarction ; therapy ; Myocytes, Cardiac ; transplantation ; Rats ; Rats, Sprague-Dawley ; Stem Cell Transplantation

OBJECTIVETo explore the feasibility of magnetic resonance imaging (MR) on detecting transplanted nanometer small superparamagnetic iron oxides (SPIO) labeled mesenchymal stem cells (MSCs) in swine model with acute myocardial infarction (MI).

METHODSMSCs isolated from swine were incubated with nanometer SPIO for 24 hours and the third-passage MSCs were labeled with DNA dye 4'-6-diamidino-2-phenylindole (DAPI) and aliphatic red fluorescent dye PKH(26)-GL. Presence of small particles of SPIO in MSCs was assessed by Prussian Blue staining and electron microscopy. Three animals in each group received SPIO-labeled MSCs (5 x 10(5); 1 x 10(6); 2 x 10(6)) and MSCs without SPIO (1 x 10(6)) injections into the infarcted myocardium approximately 1 hour following left anterior descending coronary artery. MRI (1.5-T) was performed 20 to 24 hours post infarction in all animals and the animals were subsequently sacrificed for histology 1 hour post MRI.

RESULTSIn vitro Prussian Blue staining and electron microscopy examination revealed numerous iron particles in the cytoplasm of MSCs. Low signal intensity spots with the scanning T(2)(*)WI-Flash 2d sequence were detected in all SPIO-MSCs but not in SPIO-negative-MSCs injected myocardial sites in vivo with the clinical 1.5 T scanner. Prussian blue, DAPI and PKH(26) positive cells were detected histologically in sections corresponding to low signal intensity spots area shown on MRI.

CONCLUSIONMagnetically labeled MSCs transplanted in myocardial ischemia area of swine can be visualized in vivo with a clinical 1.5-T MRI and could be used for tracking SPIO-MSCs clinically.

Animals ; Biomarkers ; Disease Models, Animal ; Ferrosoferric Oxide ; Magnetic Resonance Imaging ; methods ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; cytology ; Myocardial Infarction ; pathology ; surgery ; Myocytes, Cardiac ; Nanoparticles ; Swine