scholarly journals Resident Cardiac Stem Cells on Fibrous Poly (L-lactide) Patch Augment Cardiac Repair via in-patch Differentiation and Simultaneous Migration into Infarcted Heart Tissue

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Heiwon Kyung ◽  
Heejung Kim ◽  
Hye-Jin Chung ◽  
Seung Jin Lee ◽  
In Kyong Shim ◽  
...  
2012 ◽  
Vol 16 (11) ◽  
pp. 2549-2563 ◽  
Author(s):  
Zhuzhi Wen ◽  
Zun Mai ◽  
Haifeng Zhang ◽  
Yangxin Chen ◽  
Dengfeng Geng ◽  
...  

2011 ◽  
Vol 57 (14) ◽  
pp. E1014
Author(s):  
Behzad Nasehi Oskouei ◽  
Guillaume Lamirault ◽  
Chacko Joseph ◽  
Stephanie Landa ◽  
Marc Dauer ◽  
...  

2014 ◽  
Vol 30 (10) ◽  
pp. S185
Author(s):  
E.L. Tilokee ◽  
R. Jackson ◽  
A. Mayfield ◽  
N. Latham ◽  
B. Ye ◽  
...  

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Christina Rogge ◽  
Michael Didié ◽  
Erich Wettwer ◽  
Ursula Ravens ◽  
Ralph Graichen ◽  
...  

Engineered Heart Tissue (EHT) from neonatal rat cardiomyocytes has been used successfully as in vitro model and in cardiac repair. Here, we hypothesized that human embryonic stem cells (hESC) can be used to generate EHT with properties of native myocardium. Methods: hESC (hES3-ENVY) were differentiated in embryoid bodies, enzymatically dispersed, and subjected to EHT-generation in circular casting molds (1.5x10 6 cells, 0.4 mg collagen, 10% Matrigel/EHT; inner/outer diameter - 2/4 mm). Contractile function was assessed 10 days after casting under isometric conditions (37°C, 1.5 Hz, Tyrode’s solution). Action potentials (AP) were recorded in spontaneously contracting EHTs with intracellular electrodes (37°C, Tyrode’s solution). Calcium gradients were assessed by confocal laser scanning microscopy (CLSM) after rhod-2 loading. EHT-morphology was examined by CLSM and electron microscopy (EM). Results: hESC-EHTs contracted synchronously and spontaneously at 1.1±0.1 Hz (n=3). Increasing concentrations of extracellular calcium (0.2–2.4 mM) enhanced force of contraction from 53±8 to 199±22 μN (n=8, p<0.05; EC 50 : 0.8±0.04 mM). Isoprenaline (1 μM) at 0.4 mM calcium increased twitch tension from 61±7 to 108±15 μN (n=8, p<0.05) and shortened relaxation time from 111±6 to 87±4 ms (n=3, p<0.05). Cardiomyocytes within EHTs formed a functional syncytium composed of predominantly oriented muscle strands with a high degree of sarcomere differentiation (CLSM, EM). Cell-cell contacts through adherens junctions were identified by EM. Synchronous calcium gradient spread in spontaneously contracting EHTs indicated electrical coupling of individual cells within the multicellular constructs. AP recordings identified pacemaker cells (spontaneous diastolic depolarization) and cells with a flat phase 4 of the AP (working myocardium-like cells). Pharmacological studies demonstrated the presence and functional relevance of I Na (10–30 μM flecainide), I Ca (1 μM nisoldipine), and I Kr (1–5 μM E4031). Conclusion: Human force-generating EHT with functional and morphological properties of native myocardium can be generated. Ultimately, hESC-EHTs may constitute a model system for substance screening and could further be utilized in cardiac repair.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Robyn Jackson ◽  
Everad L Tilokee ◽  
Nicholas Latham ◽  
Bin Ye ◽  
Munir Boodhwani ◽  
...  

Background: Insulin-like growth factor (IGF-1) is a potent pro-survival cytokine that is not robustly expressed by human cardiac stem cells (CSCs). Previously, we have shown that paracrine engineering of CSCs with IGF-1 improves cell-mediated cardiac repair. Here, we explore the mechanisms underlying IGF-1 enhanced cardiac repair by CSCs. Methods/Results: Sub-culture of isolated c-Kit+, CD90+ and lineage negative cells (c-Kit-/CD90-) demonstrated that the natural low level production of IGF-1 by CSCs (149±16 pg/ml*mg) is secreted by all 3 sub-populations. After culture in hypoxic reduced serum media, lentiviral mediated over-expression of IGF-1 enhanced proliferation (population doubling time: 1.4±1.7 vs.-0.9±1.2 and -1.9±2.4 days, respectively; p≤0.01), expression of pro-survival transcripts (AKT, ERK and MAPK pathways) and pro-survival proteins (Bcl-2, Bcl-x, HIF-1a; p≤0.01) while decreasing expression of apoptotic markers (3.5±0.9 and 3.7±0.9 fold less annexin V; p≤0.01) as compared to GFP- and non-transduced CSCs. The high expression of the IGF-1 (79±3%) or the insulin receptor (61±5%) on CSCs suggests that autocrine pro-survival pre-conditioning underlies these effects. Direct and indirect co-culture of CSCs with neonatal rat ventricular cardiomyocytes (NRVMs) within hypoxic conditions demonstrated that IGF-1 promoted indirect myocardial repair by increasing NRVM viability and pro-survival signaling (Bcl2+; p≤0.01) while reducing apoptosis (annexin V+; p≤0.05) as compared GFP- or non-transduced CSCs. Transplant of CSCs genetically engineered to over-express IGF-1 into immunodeficient mice one week after infarction boosted IGF-1 content within infarcted tissue by 2.9±0.2 fold (p=0.004) and long-term engraftment (+4 weeks human alu content increased by 9.1±4 fold; p=0.05) while reducing myocardial apoptosis (3.4±0.3 and 2.5±0.5 fold reduction expression of Bax and p53, respectively; p<0.05) and long-term myocardial scarring (+ 4 weeks 2.2±0.4 fold less; p=0.01) as compared to GFP-transduced CSCs. Conclusions: Transplantation of IGF-1 enriched CSCs enhances cardiac repair by boosting transplant cell survival and reducing myocardial apoptosis to improve myocardial function and salvage of damaged myocardium.


PLoS ONE ◽  
2017 ◽  
Vol 12 (4) ◽  
pp. e0176000 ◽  
Author(s):  
Robyn Jackson ◽  
Seth Mount ◽  
Bin Ye ◽  
Audrey E. Mayfield ◽  
Vincent Chan ◽  
...  

2011 ◽  
Vol 91 (3) ◽  
pp. 369-370 ◽  
Author(s):  
F. Claes ◽  
W. Vandevelde ◽  
L. Moons ◽  
M. Tjwa

2014 ◽  
Vol 45 (6) ◽  
pp. 976-982 ◽  
Author(s):  
H. Kurazumi ◽  
T.-S. Li ◽  
Y. Takemoto ◽  
R. Suzuki ◽  
A. Mikamo ◽  
...  

Author(s):  
Prithiv K R Kumar

Loss of heart cells lead to heart attack. The blood flow slows down, eventually pumping gets effected. Several surgeries only weaken the heart. The solution to heart trouble is rather underlying mechanism to derive into regeneration. Several clinical trials have highlighted that stem cells have a promising effect in regeneration. More methods such as cardiac stem cells, bone marrow based cells, mesenchyme stem cells; embryonic stem cells have been effective to an extent. There have been some inconsistencies as well in these methods. Performance of heart has lowered; efficiency to pump blood has influence on selection of type of stem cells. However, future of therapies has to rely on technology. Not just ordinary technology, but nanotechnology. The future of heart repair and advancement of stem cells to cure any heart disease. Nanotechnology helps in understanding cellular layers of heart tissue, which plays a vital role for any heart repair or regeneration. This review discusses the aspects of nanoparticles and nanogel effect in curing heart. Nanoparticles have been effective in drug delivery, targeting particular area of cure. Meanwhile nanogel helps in navigating the drugs and creating a sustainable environment for treatment. Another concept highlighted in this review is nanopatch along with nano material or nanocells communication, helping in regenerative therapy. Thus key issues for future prospects are discussed below.


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