| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Ann Thorac Surg 2005;80:229-237
© 2005 The Society of Thoracic Surgeons
a Department of Physiology and Biophysics, College of Medicine, University of South Florida, St. Petersburg, Florida
b Zhongshan Hospital, Fudan University, Shanghai, China
Accepted for publication February 1, 2005.
* Address reprint requests to Dr Phillips, University of South Florida, 4202 East Fowler Ave, ADM200, Tampa, FL 33620-5950 (Email: ytang{at}hsc.usf.edu; iphillips{at}research.usf.edu).
Presented at the Fortieth Annual Meeting of The Society of Thoracic Surgeons, San Antonio, TX, Jan 26–28, 2004.
 |
Abstract |
|---|
 Top Abstract IntroductionMaterial and MethodsResultsCommentDiscussionAcknowledgmentsReferences |
|---|
METHODS: A transmural myocardial infarction was created by ligation of the left anterior descending coronary artery in rats. Those with an ejection fraction less than 0.70 1 week after myocardial infarction were included. Autologous MSCs (1 x 107; 0.2 mL) or culture medium (0.2 mL) was injected intramyocardially into the periinfarct zone (50 µL/injection at four sites; n = 20/group). At 2 weeks after transplantation, Western blot analysis was used to assay the paracrine factors and proapoptotic proteins. Echocardiography to assess heart function was performed on additional groups at 8 weeks after implantation.
RESULTS: The angiogenic factors basic fibroblast growth factor, vascular endothelial growth factor, and stem cell homing factor (stromal cell-derived factor -1
) increased in the MSC-treated hearts compared with medium-treated hearts. This was accompanied by a downregulation of proapoptotic protein Bax in ischemic myocardium. Similarly, capillary density increased about 40% in MSC-treated hearts compared with medium-treated hearts (p = 0.001). Left ventricular contractility, indicated by fractional shortening, improved in MSC-treated hearts at 2 months after implantation (MSCs: 48.6% ± 19.9%; medium: 18.7% ± 6.4%; p = 0.004).
CONCLUSIONS: Autologous MSC transplantation attenuates left ventricular remodeling and improves cardiac performance. The major mechanism appears to be paracrine action of the engrafted cells, increasing angiogenesis and cytoprotection.
|
Introduction |
|---|
|
TopAbstractIntroductionMaterial and MethodsResultsCommentDiscussionAcknowledgmentsReferences |
|---|
In recent years, experimental models have suggested the possibility of stem cell transplantation as an alternative strategy for a safe and long-lasting vascular regeneration [4] because bone marrow–derived mesenchymal stem cells (MSCs) have high proliferative and self-renewal capabilities [5]. Mesenchymal stem cells can also secrete a broad spectrum of angiogenic cytokines [6] and contain multipotent adult stem cells. The aim of this study was to test the effect of autologous MSC transplantation on vascular regeneration and cardioprotection. We hypothesize that MSC transplantation enhances these effects through paracrine action.
|
Material and Methods |
|---|
|
TopAbstractIntroductionMaterial and MethodsResultsCommentDiscussionAcknowledgmentsReferences |
|---|
Myocardial Infarction
Male Sprague-Dawley rats weighing 300 g underwent the procedure for MI. Under anesthesia with ketamine (50 mg/kg intraperitoneal), rats were intubated with an 18-gauge intravenous catheter with a tapered tip through a tracheotomy. Rats were mechanically ventilated with a rodent ventilator on room air. Through a left thoracotomy in the fourth intercostal space, MI was induced by ligation of the left anterior descending coronary artery 2 to 3 mm from the tip of the left auricle with a 6–0 polypropylene suture (Ethicon Inc, Somerville, NJ). Successful performance of coronary occlusion is verified by observation of the development of a pale color in the distal myocardium after ligation.
Cell Isolation, Culture, Labeling, and Implantation
Isolation and culture of adult rat MSCs was performed 7 days before MI. After rats were anesthetized with ketamine (50 mg/kg intraperitoneal), the right femur was inserted with an 18-gauge needle attached to a 10-mL syringe at the site of the ankle, and bone marrow was aspirated from the shaft of the femur and resuspended in complete medium at a cell concentration to 5 x 107 nucleated cells per milliliter. Cells were then introduced into a 25-cm2 flask and incubated with 95% air and 5% CO2 at 37°C. Medium was replaced every 4 days, and adherent cells were retained. Each primary culture was replated to two new flasks. When MSCs grew to approximately 70% confluency, cells were digested with 0.25% trypsin and 1 mmol/L EDTA for about 3 to 5 minutes at 37°C until most of the cells were detached. With two passages, homogeneous MSCs that were devoid of hematopoietic cells were used for cell transplantation.
One week after the induction of an MI, survival rats with left ventricular ejection fraction less than 0.70 on the basis of echocardiography were randomly assigned to one of two groups. One received only culture medium (n = 20, control group), the other received MSCs (n = 20, MSC group). Twenty-five microliters of 0.4% 5-bromo-2-deoxyruidine (BrdU; Sigma Chemical Co, St. Louis, MO) was added to the culture medium 48 hours before transplantation to facilitate subsequent identification. After quickly washing the cells with Hank’s buffered salt solution to remove unincorporated BrdU, we detached MSCs from the bottom of the flasks with 0.25% trypsin and 1 mmol/L EDTA and then resuspended MSCs in serum-free medium for transplantation.
For MSC implantation, rats were anesthetized, intubated, and ventilated as described above. The rat heart was exposed through a left thoracotomy, and 10 million MSCs in 0.2 mL of medium were injected into the border zone of the infarct area in four sites using a 30-gauge needle. The same volume of medium was injected in control rats in the border zone.
Western Blotting
Two weeks after cell transplantation, hearts from the MSC group and the medium group (n = 4/group) were excised for growth factors, stem cell homing factor, and proapoptosis assay. Hearts obtained were snap-frozen in liquid nitrogen. Specimens were homogenized in lysis buffer. Western blot analysis was performed using 125 µg of heart tissue extracts and electrophoresed on a 10% sodium dodecylsulfate–polyacrylamide gel. The vascular endothelial growth factor (VEGF) protein was probed with monoclonal anti-VEGF antibody (BD Pharmingen, Palo Alto, CA). The basic fibroblast growth factor (bFGF) protein was probed with monoclonal anti-bFGF antibody (Chemicon, Temecula, CA). The stromal cell–derived factor-1 (SDF-1) was probed with monoclonal anti-SDF-1 antibody (R&D Systems, Minneapolis, MN). Apoptosis was assayed by polyclonal anti-Bax antibody (Upstate, Charlottesville, VA). The internal control protein glyceraldehyde-3-phosphate dehydrogenase was probed with glyceraldehyde-3-phosphate dehydrogenase antibody (Chemicon). The membrane was subsequently blocked with 5% nonfat dry milk in Tris-buffered saline containing 0.05% Tween-20. Immunoreactivity was visualized using horseradish peroxidase–conjugated secondary antibodies with enhanced chemiluminescence kit (Amersham, Piscataway, NJ). Bands on Western blots were quantified by densitometry using Quantity One software (Bio-Rad, Hercules, CA).
Echocardiogram
Cardiac function was studied by transthoracic echocardiography at 1 week after MI (baseline) and 2 months after transplantation. M mode measurement was performed with a commercially available 12-MHz transducer system designed for cardiac ultrasonic studies in mouse models and connected to an ultrasound device (HP Sonos 5500; Agilent Technologies, Andover, MA). As a measure of left ventricular (LV) function, the percent fractional shortening (FS) was calculated as follows: where LVEDd is LV end-diastolic dimension and LVESd is LV end-systolic dimension. Dimensions were measured between the anterior wall and the posterior wall from the short-axis view just below the level of the papillary muscle.
All measurements were averaged on three consecutive cardiac cycles and were analyzed by two independent observers who were blinded to the treatment status of the animals.
Histology
Two weeks after transplantation, the hearts were embedded in Tissue-Tek OCT compound (Sakura Fineteck, Torrance, CA) and sectioned using cryostat. A horizontal 5-µm section at the papillary muscle level was stained with Masson trichrome using commercial kit (Sigma Chemical Co) and used to evaluate the fibrotic deposition in the mouse hearts. Fibrillar collagen was identified in the Masson trichrome-stained sections by its blue colored appearance. Sections were used to estimate the areas of the fibrous infarct region on the endocardial and epicardial surfaces as a proportion of the total LV area by an image analysis system (AnalySIS, Soft Imaging System Corp, Lakewood, CO). Capillary density was assessed in 12 rats (6 in each group); 5-µm sections of hearts were incubated with Griffonia Bandeiraea simplicifolia Isolectin B4 (GSL-I-B4, Vector Laboratories, Burlingame, CA) in 1:50 dilution, followed by a second incubation with streptavidin-peroxidase. Finally, the capillaries were visualized by 3,3'-diaminobenzidine tetrachloride using DAKO ARK Peroxidase kit (DAKO, Carpinteria, CA). Capillaries were counted at a magnification of x20 using an Olympus microscope. Border zones around the injection site were taken to count capillaries in the ventricle by an image analysis system. The quality of the computer analysis was checked against manual counting. The number of vessels was counted in blind fashion on 48 sections (two fields per slide, two slides per heart) in the border zone. The BrdU-positive MSCs in the cultured dish and in the grafted myocardium were revealed using a BrdU staining kit (Zymed Laboratories Inc, South San Francisco, CA) according to commercial protocol.
Statistical Analysis
All values are expressed as mean ± standard deviation. Comparison between groups was by Student’s t test. A p value less than 0.05 was considered significant.
|
Results |
|---|
|
TopAbstractIntroductionMaterial and MethodsResultsCommentDiscussionAcknowledgmentsReferences |
|---|
|
|
expression was greater than that in control rats at 2 weeks (p = 0.019, n = 4; Fig 3C).
|
Left Ventricular Remodeling and Functional Assessment
Masson trichrome staining showed a marked reduction of infarct size in the MSC graft group compared with the medium group in the infarcted myocardium (20.9% ± 5.2% versus 35.9% ± 7.1%; p = 0.002, n = 6; Figs 4E, 4F, 4I). Interestingly, most of the myocardial structure in the border zone was intact and accompanied by many new blood vessels in MSC-treated hearts whereas the myocardial structure was chaotic in the medium-treated hearts, indicting that MSC engraftment attenuated LV remodeling after MI (Figs 4G, 4H).
|
|
|
Comment |
|---|
|
TopAbstractIntroductionMaterial and MethodsResultsCommentDiscussionAcknowledgmentsReferences |
|---|
leads to efficient vascular regeneration and also attenuates the apoptotic pathway. These paracrine actions account for reduced remodeling and recovery of cardiac performance.
We demonstrated that graft MSCs in ischemic myocardium secrete SDF-1. This cytokine may have an effect on homing of circulating endothelial progenitor cells. Recently it has become evident that the SDF-1–chemokine (CXC motif) receptor 4 signaling axis plays an essential role in the homing and engraftment of hematopoietic stem cells. These cells have the capacity to proliferate, migrate, and differentiate into various mature cell types, including endothelial progenitor cells [7], which possess the ability to mature into the cells that line the lumen of blood vessels [8]. Circulating endothelial progenitor cells exhibit a chemotactic and chemokinetic response to an SDF-1 gradient [9] because chemokine (CXC motif) receptor 4 is highly expressed on endothelial progenitor cells [10–13]. Endothelial progenitor cells play an important role in endothelium maintenance, being implicated in both reendothelialization and neovascularization [14]. We have shown that the overexpression of SDF-1 levels in ischemic heart by pCMV–SDF-1 administration can trigger hematopoietic stem cell mobilization to the heart through a positive gradient from the peripheral blood or bone marrow to the heart [15]. However, endogenous SDF-1 as a "healing pathway" only lasts for a short time. The secretion of SDF-1 is increased in the heart early after MI [16], but returned to baseline by 4 to 7 days [17]. Thus, reestablishing SDF-1 expression at a time remote from the MI may be an ideal strategy for us to amplify the healing process for an extended time after tissue injury. Although it has been reported that marrow stromal cells of mesenchymal origin can secrete high amounts of SDF-1 in the bone marrow [18], our results show that graft MSCs in ischemic heart secrete SDF-1 in ischemic myocardium. Owing to the self-renewing nature of MSCs, graft MSCs can work as an SDF-1 pool in the ischemic myocardium, which may release SDF-1 continuously. Long-term SDF-1 secretion helps with endothelial progenitor cell homing to stimulate neovascularization and is beneficial for LV remodeling [19].
Another important finding in this study is that accompanying the growth of small size to larger-sized capillaries in the border zone of the infarct area after autologous MSC implantation, apoptotic proteins in the ischemic myocardium are regulated in a beneficial pathway by downregulating a proapoptotic protein. This may be an important pathway involved in cytoprotection. Cell apoptosis from the activation of proapoptotic signal transduction pathways reportedly accounts for at least half of the total cell destruction during MI [20, 21]. We evaluated the level of an important proapoptotic protein—Bax of the Bcl family. We found that Bax was downregulated in myocardium treated with MSCs compared with myocardium treated with medium. As we previously showed [22], the terminal deoxynucleotidyl transferase biotin–deoxyuridine triphosphate nick end labeling–positive cardiomyocytes were also decreased in MSC-treated myocardium compared with medium-treated myocardium, indicating that MSC-mediated cytoprotection is related to regulation of the apoptotic pathway.
Paracrine actions of graft MSCs also reflect on secretion of angiogenic factors, such as VEGF and bFGF. Vascular endothelial growth factor is a critical angiogenic factor, which could not only contribute to endothelial lineage cell survival through VEGF-mediated phosphorylation of protein kinase B and endothelial nitric oxide synthase proteins [23–25] but also accelerate the development of microvessels and enhance regional blood flow in ischemic tissue [26]. Although hypoxia can increase VEGF and bFGF expression and angiogenesis in ischemic myocardium, this natural process is inefficient for repair because it cannot provide enough blood supply to compensate overloaded ischemic heart tissue [27]. Our results show that MSC grafting induced a higher level of VEGF and bFGF synthesis and expression in ischemic hearts than the levels of VEGF and bFGF synthesis induced by endogenous ischemia in medium-treated control hearts. Kamihata and colleagues [28] have reported that bone marrow mononuclear cells that survived engrafting can synthesize angiogenic factors such as VEGF, bFGF, and angiopoietin-1 to induce angiogenesis in the ischemic myocardium. Thus, our results expanded the finding of Kamihata’s group through finding the role of graft MSCs in SDF-1 secreting, which suggests another important mechanism for angiogenesis–SDF-1–mediated vascular regeneration. This finding is also important for selecting cell therapy strategy because genetic modification of MSCs with angiogenic growth factor genes for neovascularization may be unnecessary, although gene modification can bring many benefits for other cell types, such as skeletal myoblast or heart cells [29].
Although MSCs do not express endothelial cell surface markers in the undifferentiated state, recent evidence demonstrated that MSCs have the ability to differentiate from mesoderm-derived endothelial cells [30] and transdifferentiate in vivo into CD31+ endothelial cells [31], and thus play a potential role in microcirculation remodeling [32, 33]. Recently, Davani and associates [34] used a rat cellular cardiomyoplasty model to demonstrate that engrafted MSCs participate in the process of endothelial differentiation. This result is consistent with our findings that some graft MSCs can integrate into new blood vessels in ischemic myocardium.
Simultaneously, paracrine actions are effective in ameliorating LV remodeling and enhancing the recovery of cardiac function. Previous studies using MSCs for cell therapy contributed functional recovery to myocardial regeneration [35–37]. Although some engrafted MSCs can express specific cardiac markers, such as connexin43 and cardiac troponin I, the frequency of this transdifferentiation is low, and only limited gap junctions were formed between grafted and native cells. There must be another possible mechanism for functional recovery. Overloaded and hibernating cardiomyocytes are facilitated to undergo cell necrosis or apoptosis, which may lead to LV remodeling and heart failure [38]. Graft MSCs can secret potent protective factors for vascular regeneration and downregulation of proapoptotic proteins in overloading and hibernating myocardium. It is reasonable to postulate that paracrine actions are responsible for MSC-mediated repair in ischemic hearts.
In summary, engrafting MSCs into ischemic heart has a beneficial effect, which may be attributable to paracrine action. Our data suggest that MSCs secrete a number of angiogenic factors, stem cell homing factor, and down-regulate proapoptotic proteins that would account for the reduced LV remodeling and improved cardiac performance.
|
Discussion |
|---|
|
TopAbstractIntroductionMaterial and MethodsResultsCommentDiscussionAcknowledgmentsReferences |
|---|
DR TANG: It is difficult to determine the amount of mesenchymal stem cells necessary for therapeutic angiogenesis; however, most investigators found microvessel growth even if they implanted a different amount of cells.
DR PAUL KURLANSKY (Miami Beach, FL): Two questions, which may or may not be related. First of all, congratulations on some very interesting work. I was a little surprised to find that ventricular function actually improved compared with baseline. You still have an infarcted heart. You may have impaired the remodeling process or ameliorated the remodeling process, but I would not have expected ventricular function to therefore improve compared with baseline. I would have expected it to be less impaired. So I was wondering if you had any explanation as to why it actually improved?
A second question is that in a similar model some investigators have actually found, in addition to neovascularization or angiogenesis, that there is a stimulation of mitosis of cardiomyocytes, and I was wondering if you had looked at this or found it? Thank you.
DR TANG: Thank you for your comments. For the first question, I attributed left ventricular function improvement to left ventricular remodeling because hibernated myocardium is important for recovery of left ventricular function and amelioration of left ventricular remodeling. The basal heart function was detected at 1 week after myocardial infarction by echocardiogram.
To the second one, I have not detected mitosis of cardiomyocytes.
DR AMIT PATEL (Pittsburgh, PA): Two questions. First, in your injection of the myocardium did you look at the amount of cells that you lost by systemic injection directly into the ventricle or were these injections performed with echo guidance to decrease the number of cells lost systemically?
Also, did you look for an increase in ventricular wall thickness once you injected these cells? You observed that the ejection fraction (EF) improved from 0.56 to 0.80 almost in all your experimental models. Did you see any echo evidence of septal thickness or actual left ventricular (LV) free wall thickness to show that there was an increase in the amount of myocardium or the muscle mass, or was it strictly an effect of angiogenesis?
DR TANG: Thank you for your comments. Actually we injected cells intramyocardially into the border muscle surrounding the infarct area. We can find edema in the injected site, and there was little systemic loss.
And the second question, in the echocardiogram, the global function was improved. It is hard to measure the local muscle mass precisely because of the small size of rats.
MR REX STANBRIDGE (London, UK): I believe there was some suggestion in previous work that injection doesn’t necessarily only work in the area where it is injected, but there is sometimes dissemination into other parts of the heart muscle, and I wondered if you had looked at other parts of the heart muscle other than the infected border zone, to see if there had been improved manifestation of vascular endothelial growth factor (VEGF) or anything else, because that might help explain why the ejection fraction becomes better at the end of the time, better than control?
DR TANG: It is possible.
DR SHUMWAY: Did you look at the other areas of the heart besides the areas where you just injected?
DR TANG: Yes.
MR STANBRIDGE: And did you find anything?
DR SHUMWAY: Did you see other parts of the heart besides the area where you did inject?
DR TANG: Yes, there is more VEGF expression and less terminal deoxynucleotidyl transferase biotin–deoxyuridine triphosphate nick end labeling (TUNEL) -positive cells in the normal area compared with the control. I have a picture that shows not only the scar area but the border area and the normal area where VEGF expression was increased.
MR STANBRIDGE: Right. So that is quite important then that you are seeing VEGF expression improved in the normal areas of the heart separate and distant from where the injection was made.
|
Acknowledgments |
|---|
|
TopAbstractIntroductionMaterial and MethodsResultsCommentDiscussionAcknowledgmentsReferences |
|---|
|
References |
|---|
|
TopAbstractIntroductionMaterial and MethodsResultsCommentDiscussionAcknowledgmentsReferences |
|---|
This article has been cited by other articles:
|
|
 |
|
  P. Dufourcq, B. Descamps, N. F. Tojais, L. Leroux, P. Oses, D. Daret, C. Moreau, J.-M. D. Lamaziere, T. Couffinhal, and C. Duplaa Secreted Frizzled-Related Protein-1 Enhances Mesenchymal Stem Cell Function in Angiogenesis and Contributes to Neovessel Maturation Stem Cells, November 1, 2008; 26(11): 2991 - 3001. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. da Silva Meirelles, A. I. Caplan, and N. B. Nardi In Search of the In Vivo Identity of Mesenchymal Stem Cells Stem Cells, September 1, 2008; 26(9): 2287 - 2299. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Psaltis, A. C.W. Zannettino, S. G. Worthley, and S. Gronthos Concise Review: Mesenchymal Stromal Cells: Potential for Cardiovascular Repair Stem Cells, September 1, 2008; 26(9): 2201 - 2210. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Atoui, D. Shum-Tim, and R. C.J. Chiu Myocardial regenerative therapy: immunologic basis for the potential "universal donor cells". Ann. Thorac. Surg., July 1, 2008; 86(1): 327 - 334. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Dudley Jr and D. Simpson An Imperfect Syllogism: Granulocyte Colony-Stimulating Factor Mobilization and Cardiac Regeneration J. Am. Coll. Cardiol., April 15, 2008; 51(15): 1438 - 1439. [Full Text] [PDF]
|
|
|
|
|
|
R. W. Grauss, J. van Tuyn, P. Steendijk, E. M. Winter, D. A. Pijnappels, B. Hogers, A. C. Gittenberger-De Groot, R. van der Geest, A. van der Laarse, A. A.F. de Vries, et al. Forced Myocardin Expression Enhances the Therapeutic Effect of Human Mesenchymal Stem Cells After Transplantation in Ischemic Mouse Hearts Stem Cells, April 1, 2008; 26(4): 1083 - 1093. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Chachques, J. C. Trainini, N. Lago, M. Cortes-Morichetti, O. Schussler, and A. Carpentier Myocardial Assistance by Grafting a New Bioartificial Upgraded Myocardium (MAGNUM Trial): Clinical Feasibility Study Ann. Thorac. Surg., March 1, 2008; 85(3): 901 - 908. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Atoui, J.-F. Asenjo, M. Duong, G. Chen, R. C.-J. Chiu, and D. Shum-Tim Marrow Stromal Cells as Universal Donor Cells for Myocardial Regenerative Therapy: Their Unique Immune Tolerance Ann. Thorac. Surg., February 1, 2008; 85(2): 571 - 579. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. W. Grauss, E. M. Winter, J. van Tuyn, D. A. Pijnappels, R. V. Steijn, B. Hogers, R. J. van der Geest, A. A. F. de Vries, P. Steendijk, A. van der Laarse, et al. Mesenchymal stem cells from ischemic heart disease patients improve left ventricular function after acute myocardial infarction Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2438 - H2447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Simpson, H. Liu, T.-H. M. Fan, R. Nerem, and S. C. Dudley Jr. A Tissue Engineering Approach to Progenitor Cell Delivery Results in Significant Cell Engraftment and Improved Myocardial Remodeling Stem Cells, September 1, 2007; 25(9): 2350 - 2357. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-C. Hung, R. R. Pochampally, S.-C. Chen, S.-C. Hsu, and D. J. Prockop Angiogenic Effects of Human Multipotent Stromal Cell Conditioned Medium Activate the PI3K-Akt Pathway in Hypoxic Endothelial Cells to Inhibit Apoptosis, Increase Survival, and Stimulate Angiogenesis Stem Cells, September 1, 2007; 25(9): 2363 - 2370. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Li, N. Ma, L.-L. Ong, C. Nesselmann, C. Klopsch, Y. Ladilov, D. Furlani, C. Piechaczek, J. M. Moebius, K. Lutzow, et al. Bcl-2 Engineered MSCs Inhibited Apoptosis and Improved Heart Function Stem Cells, August 1, 2007; 25(8): 2118 - 2127. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. A. Potapova, G. R. Gaudette, P. R. Brink, R. B. Robinson, M. R. Rosen, I. S. Cohen, and S. V. Doronin Mesenchymal Stem Cells Support Migration, Extracellular Matrix Invasion, Proliferation, and Survival of Endothelial Cells In Vitro Stem Cells, July 1, 2007; 25(7): 1761 - 1768. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Togel, K. Weiss, Y. Yang, Z. Hu, P. Zhang, and C. Westenfelder Vasculotropic, paracrine actions of infused mesenchymal stem cells are important to the recovery from acute kidney injury Am J Physiol Renal Physiol, May 1, 2007; 292(5): F1626 - F1635. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. H. Wu, B. Zhou, C. T. Yu, B. Cui, S. H. Lu, Z. C. Han, and Y. L. Liu Therapeutic Potential of Human Umbilical Cord Derived Stem Cells in a Rat Myocardial Infarction Model Ann. Thorac. Surg., April 1, 2007; 83(4): 1491 - 1498. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. L. Tang and M. I. Phillips Invited commentary Ann. Thorac. Surg., April 1, 2007; 83(4): 1499 - 1500. [Full Text] [PDF]
|
|
|
|
|
|
J. Feng and F. W. Sellke Invited commentary Ann. Thorac. Surg., March 1, 2007; 83(3): 1119 - 1120. [Full Text] [PDF]
|
|
|
|
|
|
S. Schenk, N. Mal, A. Finan, M. Zhang, M. Kiedrowski, Z. Popovic, P. M. McCarthy, and M. S. Penn Monocyte Chemotactic Protein-3 Is a Myocardial Mesenchymal Stem Cell Homing Factor Stem Cells, January 1, 2007; 25(1): 245 - 251. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Xiang, J. Wang, E. Kaplan, P. Oettgen, L. Lipsitz, J. P. Morgan, and J.-Y. Min Antiapoptotic Effect of Implanted Embryonic Stem Cell-Derived Early-Differentiated Cells in Aging Rats After Myocardial Infarction J. Gerontol. A Biol. Sci. Med. Sci., December 1, 2006; 61(12): 1219 - 1227. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. H. Wu, Y. L. Liu, B. Zhou, and Z. C. Han Cellular therapy and myocardial tissue engineering: the role of adult stem and progenitor cells Eur. J. Cardiothorac. Surg., November 1, 2006; 30(5): 770 - 781. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 |
