Effects of autologous bone marrow stem cell transplantation on beta-adrenoceptor density and electrical activation pattern in a rabbit model of non-ischemic heart failure

Dhein, Stefan; Garbade, Jens; Rouabah, D; Abraham, Getu; Ungemach, Fritz-Rupert; Schneider, Katja; Ullmann, C.; Aupperle, H.; Gummert, Jan; Mohr, Friedrich–Wilhelm

doi:10.1186/1749-8090-1-17

Cited by 31 publications

(27 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The impact of MSC administration on cell contractility due to paracrine mechanisms has also been observed by our group and others [31, 50]. This may due to the consequence of cardiomyocyte protection and/or direct release of inotropic factors.…”

Section: Mesenchymal Stem Cellssupporting

confidence: 78%

Paracrine mechanisms of stem cell reparative and regenerative actions in the heart

Mirotsou

Jayawardena

Schmeckpeper

et al. 2011

Journal of Molecular and Cellular Cardiology

426

317

View full text Add to dashboard Cite

Stem cells play an important role in restoring cardiac function in the damaged heart. In order to mediate repair, stem cells need to replace injured tissue by differentiating into specialized cardiac cell lineages and/or manipulating the cell and molecular mechanisms governing repair. Despite early reports describing engraftment and successful regeneration of cardiac tissue in animal models of heart failure, these events appear to be infrequent and yield too few new cardiomyocytes to account for the degree of improved cardiac function observed. Instead, mounting evidence suggests that stem cell mediated repair takes place via the release of paracrine factors into the surrounding tissue that subsequently direct a number of restorative processes including myocardial protection, neovascularization, cardiac remodeling, and differentiation. The potential for diverse stem cell populations to moderate many of the same processes as well as key paracrine factors and molecular pathways involved in stem cell-mediated cardiac repair will be discussed in this review.

show abstract

Section: Mesenchymal Stem Cellssupporting

confidence: 78%

Paracrine mechanisms of stem cell reparative and regenerative actions in the heart

Mirotsou

Jayawardena

Schmeckpeper

et al. 2011

Journal of Molecular and Cellular Cardiology

426

317

View full text Add to dashboard Cite

show abstract

“…MSC injection improved clinical heart function 7 and ß-receptor expression 5 but induced myocardial fibrosis and increased MMP expression. In contrast, injection of CM resulted not in better heart function 7 but in a higher degree of myocardial fibrosis and TIMP-3 expression than MSC injection did.…”

mentioning

confidence: 99%

Effects of Autologous Stem Cells on Immunohistochemical Patterns and Gene Expression of Metalloproteinases and Their Tissue Inhibitors in Doxorubicin Cardiomyopathy in a Rabbit Model

Aupperle¹,

Garbade

Schubert

et al. 2007

Vet Pathol

View full text Add to dashboard Cite

Abstract. This study aims to investigate the expression of metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in chronic doxorubicin cardiomyopathy in a rabbit model and to evaluate the effects of bone marrow-derived mesenchymal stem cell (MSC) transplantation in this disease. Thirtynine 3-month-old New Zealand rabbits were divided into 4 groups: group 1 (n 5 9) was the untreated control. Groups 2-4 were treated with 6 weeks of doxorubicin (3 mg/kg). Group 2 (n 5 6) received no further treatment. In group 3 (n 5 9), animals were treated with culture medium (CM) alone. In group 4 (n 5 15), autologous MSCs (1.5-2.0 3 10 6 /ml) were injected in the left ventricular (LV) wall. Hearts were stained with HE and picrosirius red. MMP-1, -2, -3 and -9 and TIMP-2 and -3 were detected immunohistochemically. The mRNA levels were determined by real-time polymerase chain reaction. The results confirmed that doxorubicin treatment resulted in minimal myocardial fibrosis and showed that expression of MMPs increased and TIMP-3 decreased. The injection procedure resulted in increased myocardial fibrosis in groups 3 and 4. After MSC injection, MMP-1, MMP-2, and TIMP-3 expression was higher than that in group 2. CM injection led to more fibrosis, elevated TIMP-3, but diminished MMP-1 and MMP-2 expression compared with MSC injection. The mRNA levels of MMPs and TIMPs were not significantly different among all groups. In conclusion, chronic doxorubicin cardiomyopathy was characterized by increased MMP and decreased TIMP-3 expression. MSCs injection into the LV resulted in marked differences of collagen content and MMP/TIMP expression in the whole heart, although significant numbers of living MSCs were not detected after 4 weeks.

show abstract

“…Existing evidence suggests that ischemia and hypoxia, inflammation, apoptosis, oxidative stress, and neuroendocrine activation together create a grim and adverse microenvironment in the infracted myocardium to threaten the survival of implanted stem cells [8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27]. Clearly, maximizing the survival rate of transplanted cells is a critical step towards maximizing the potential of stem cell therapy for AMI.…”

Section: Discussionmentioning

confidence: 99%

“…The procedures for isolation and culturing of BMSCs were essentially the same as described in detail elsewhere [22]. Briefly, two days prior to AMI, 2 ml bone marrow was collected from femur under strictly sterile conditions, and diluted and dispersed by pipetting in phosphate buffered saline (PBS).…”

Section: Methodsmentioning

confidence: 99%

Atorvastatin Improves Microenvironment to Enhance the Beneficial Effects of BMSCs Therapy in a Rabbit Model of Acute Myocardial Infarction

Tian

et al. 2013

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: To investigate the beneficial effects of atorvastatin added to the cell therapy with bone marrow-derived mesenchymal stromal cells (BMSCs) in a rabbit model of acute myocardial infarction (AMI). Methods: Rabbits were randomly divided into control group (n=10), bone marrow stem cells transplantation group (n=10), and BMSCs + atorvastatin group (n=10). AMI was established by ligating the left descending coronary artery. The left ventricular (LV) function was evaluated by echocardiography. H&E staining and Masson's Trichrome staining were performed to evaluate inflammatory cell infiltration and cardiac fibrosis. Immunohistochemistry and TUNEL were conducted to assess survival, differentiation, and apoptosis of transplanted cells and cardiomyocytes. Results: BMSCs decreased LV systolic and diastolic diameters and increased LV ejection fractions, LV fractional shortening, LV systolic pressure and LV end-diastolic pressure. Atorvastatin synergistically enhanced the BMSCs-induced improvements of ischemic cardiac dysfunction. Atorvastatin reduced inflammatory cell infiltration, cardiac fibrosis, and derangement of myocardial morphology/structure. Atorvastatin added a protective effect to cardiomyocytes against apoptotic cell death in infarct and peri-infarct areas, and also increased the survival rate of implanted BMSCs in acute myocardial ischemia. Atorvastatin also promoted cardiac differentiation of implanted BMSCs in infarct myocardium. Conclusion: Atorvastatin acts to improve the microenvironment both by synergistically enhancing the existing effects of BMSCs and by adding new therapeutic effects to BMSCs transplantation, and this combinational therapy is a superior cell/pharmacological therapeutic approach that merits future preclinical and clinical studies.

show abstract

Effects of autologous bone marrow stem cell transplantation on beta-adrenoceptor density and electrical activation pattern in a rabbit model of non-ischemic heart failure

Abstract: Background: Since only little is known on stem cell therapy in non-ischemic heart failure we wanted to know whether a long-term improvement of cardiac function in non-ischemic heart failure can be achieved by stem cell transplantation.

Cited by 31 publications

References 43 publications

Paracrine mechanisms of stem cell reparative and regenerative actions in the heart

Paracrine mechanisms of stem cell reparative and regenerative actions in the heart

Effects of Autologous Stem Cells on Immunohistochemical Patterns and Gene Expression of Metalloproteinases and Their Tissue Inhibitors in Doxorubicin Cardiomyopathy in a Rabbit Model

Atorvastatin Improves Microenvironment to Enhance the Beneficial Effects of BMSCs Therapy in a Rabbit Model of Acute Myocardial Infarction

Contact Info

Product

Resources

About