Transmyocardial laser revascularization combined with intramyocardial endothelial progenitor cell transplantation in patients with intractable ischemic heart disease ineligible for conventional revascularization: preliminary results in a highly selected small patient cohort

2009 ◽  
Vol 56 (S 01) ◽  
Author(s):  
EI Charitos ◽  
J Babin-Ebell ◽  
EG Kraatz ◽  
HA Sier ◽  
KF Wagner ◽  
...  
Keyword(s):  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Cell Transplantation ◽  
Endothelial Progenitor Cell ◽  
Progenitor Cell ◽  
Ischemic Heart ◽  
Endothelial Progenitor ◽  
Preliminary Results ◽  
Transmyocardial Laser Revascularization ◽  
Small Patient

Abstract 42: In Vivo Differentiation of Epigenetically Reprogrammed Human Endothelial Progenitor Cells into Cardiomyocytes Enhances Functional and Anatomical Postinfarct Myocardial Repair

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Melissa A Thal ◽  
Prasanna Krishnamurthy ◽  
Alexander R Mackie ◽  
Eneda Hoxha ◽  
Erin Lambers ◽  
...  
Keyword(s):  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Ischemic Heart ◽  
Specific Gene ◽  
Myocardial Repair ◽  
Endothelial Progenitor ◽  
Human Cd34 ◽  
Cd34 Cells

Currently, bone marrow derived endothelial progenitor cells (human CD34+ cells, EPC) are being used clinically to improve vascularization in patients with ischemic heart disease. While it is generally accepted that CD34+ cells predominantly work through a paracrine mechanism, there exists no convincing evidence that these cells trans-differentiate into functional cardiomyocytes (CMC). Since ischemic heart disease leads to substantial loss of CMC, improving cardiomyogenic plasticity of an existing autologous cell therapy is of obvious import. EPC and CMC both differentiate from a common mesodermal progenitor however; during EC-specific lineage differentiation, CMC specific genes are epigenetically silenced. We hypothesized that reprogramming of CD34+ cells using small molecules targeting key epigenetic repressive marks may recapitulate their cardiomyogenic potential. Human CD34+ EPCs were treated with inhibitors of histone deacetylases (valproic acid) for 24 hours followed by an additional 24 hours with the DNA methyltransferase inhibitor (5-Azacytidine). This forty-eight hour treatment led to the reactivation of pluripotency associated and CMC specific mRNA expression while EC specific gene expression was maintained. Intra-myocardial transplantation of a sub-therapeutic dose of reprogrammed CD34+ cells in an acute myocardial infarction mouse model showed significant improvement in LV function compared to the same number of control CD34+ cells that are therapeutically equivalent to no treatment at all. This was histologically supported by de novo CMC differentiation. In addition to increased cardiomyogenic plasticity, drug treatment also enhanced the inherent therapeutic capacity of the CD34+ cells as shown by reduced fibrosis, increased capillary density, increased proliferation, increased cell survival and increased secretion of angiogenic factors. Taken together, our results suggest that epigenetically reprogrammed CD34+ cells are “super-CD34+ cells” that have an enhanced paracrine effect, display a more plastic phenotype and improve post-infarct cardiac repair by both neo-cardiomyogenesis and neovascularization.

scholarly journals Influence of Conventional Cardiovascular Risk Factors and Lifestyle Characteristics on Cardiovascular Disease After Hematopoietic Cell Transplantation

2014 ◽  
Vol 32 (3) ◽  
pp. 191-198 ◽  
Author(s):  
Eric J. Chow ◽  
K. Scott Baker ◽  
Stephanie J. Lee ◽  
Mary E.D. Flowers ◽  
Kara L. Cushing-Haugen ◽  
...  
Keyword(s):  
Physical Activity ◽  
Risk Factors ◽  
Cardiovascular Disease ◽  
Heart Disease ◽  
Cardiovascular Risk ◽  
Ischemic Heart Disease ◽  
Cardiovascular Risk Factors ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Ischemic Heart

Purpose To determine the influence of modifiable lifestyle factors on the risk of cardiovascular disease after hematopoietic cell transplantation (HCT). Patients and Methods HCT survivors of ≥ 1 year treated from 1970 to 2010 (n = 3,833) were surveyed from 2010 to 2011 on current cardiovascular health and related lifestyle factors (smoking, diet, recreational physical activity). Responses (n = 2,362) were compared with those from a matched general population sample (National Health and Nutrition Examination Survey [NHANES]; n = 1,192). Results Compared with NHANES participants, HCT survivors (median age, 55.9 years; median 10.8 years since HCT; 71.3% allogeneic) had higher rates of cardiomyopathy (4.0% v 2.6%), stroke (4.8% v 3.3%), dyslipidemia (33.9% v 22.3%), and diabetes (14.3% v 11.7%; P < .05 for all comparisons). Prevalence of hypertension was similar (27.9% v 30.0%), and survivors were less likely to have ischemic heart disease (6.1% v 8.9%; P < .01). Among HCT survivors, hypertension, dyslipidemia, and diabetes were independent risk factors for ischemic heart disease and cardiomyopathy, and smoking was associated with ischemic heart disease and diabetes (odds ratios [ORs], 1.8 to 2.1; P = .02). Obesity was a risk factor for post-transplantation hypertension, dyslipidemia, and diabetes (ORs ≥ 2.0; P < .001). In contrast, lower fruit/vegetable intake was associated with greater risk of dyslipidemia and diabetes (ORs, 1.4 to 1.8; P ≤ .01), and lower physical activity level was associated with greater risk of hypertension and diabetes (ORs, 1.4 to 1.5; P < .05). Healthier lifestyle characteristics among HCT survivors attenuated risk of all cardiovascular conditions assessed. Conclusion Attention of clinicians to conventional cardiovascular risk factors and modifiable lifestyle characteristics offers hope of reducing serious cardiovascular morbidity after HCT.

scholarly journals Role of host tissues for sustained humoral effects after endothelial progenitor cell transplantation into the ischemic heart

2007 ◽  
Vol 204 (13) ◽  
pp. 3257-3269 ◽  
Author(s):  
Hyun-Jai Cho ◽  
Namho Lee ◽  
Ji Yoon Lee ◽  
Yong Jin Choi ◽  
Masaaki Ii ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Endothelial Progenitor Cell ◽  
Progenitor Cell ◽  
Biological Effects ◽  
Expression Patterns ◽  
Therapeutic Effects ◽  
Myocardial Repair ◽  
Endothelial Progenitor ◽  
Humoral Factors ◽  
Host Tissues

Noncellular differentiation effects have emerged as important mechanisms mediating therapeutic effects of stem or progenitor cell transplantation. Here, we investigated the expression patterns and sources of humoral factors and their regional and systemic biological effects after bone marrow (BM)-derived endothelial progenitor cell (EPC) transplantation into ischemic myocardium. Although most of the transplanted EPCs disappeared within a week, up-regulation of multiple humoral factors was sustained for longer than two weeks, which correlated well with the recovery of cardiac function. To determine the source of the humoral factors, we injected human EPCs into immunodeficient mice. Whereas the expression of human EPC (donor)-derived cytokines rapidly decreased to a nondetectable level within a week, up-regulation of mouse (recipient)-derived cytokines, including factors that could mobilize BM cells, was sustained. Histologically, we observed higher capillary density, a higher proliferation of myocardial cells, a lower cardiomyocyte apoptosis, and reduced infarct size. Furthermore, after EPC transplantation, BM-derived stem or progenitor cells were increased in the peripheral circulation and incorporated into the site of neovascularization and myocardial repair. These data indicate that myocardial EPC transplantation induces humoral effects, which are sustained by host tissues and play a crucial role in repairing myocardial injury.

Sign in / Sign up

Export Citation Format

Share Document