scholarly journals Myocardial Restoration: Is It the Cell or the Architecture or Both?

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Duc Thang Vu ◽  
Theo Kofidis
Keyword(s):  
Myocardial Infarction ◽  
Tissue Engineering ◽  
Clinical Trials ◽  
Cell Therapy ◽  
Cardiac Regeneration ◽  
Developed Countries ◽  
Cardiac Cell ◽  
Cardiac Cell Therapy ◽  
Promising Solution ◽  
Structural Aspects

Myocardial infarction is the leading cause of death in developed countries. Cardiac cell therapy has been introduced to clinical trials for more than ten years but its results are still controversial. Tissue engineering has addressed some limitations of cell therapy and appears to be a promising solution for cardiac regeneration. In this review, we would like to summarize the current understanding about the therapeutic effect of cell therapy and tissue engineering under purview of functional and structural aspects, highlighting actual roles of each therapy towards clinical application.

Abstract 3821: Mesp1 Mediates Cardiovascular Differentiation By Dkk-1 Driven Inhibition Of Wnt-signaling And Is A Suitable Tool For Isolation Of Es Cell Derived Cardiovascular Progenitors

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Robert David
Keyword(s):  
Tissue Engineering ◽  
Cell Therapy ◽  
Es Cells ◽  
Expression Patterns ◽  
Tumor Formation ◽  
High Yield ◽  
Specific Cell ◽  
Cardiac Cell ◽  
Regulatory Cascade ◽  
Cardiac Cell Therapy

We have recently shown that MesP1 is a cardiac key transcription factor sufficient to induce ectopic beating heart tissue. MesP1 overexpression in ES cells results in significantly increased cardiovasculogenesis. Our results revealed a prominent function of MesP1 within a gene regulatory cascade causing Dkk-1 mediated blockage of wnt signalling. MesP1 may become a tool to preprogram ES cells for cardiac cell therapy and tissue engineering. In addition to directed differentiation, future cardiac cell therapy strategies will require protocols for a high-yield isolation of specific cell types to avoid the hazard of teratoma and tumor formation. Therefore we have developed a method for magnetic cell sorting (MACS) of ES cells expressing a human CD4 surface marker lacking its intracellular domain (ΔCD4) under control of transgenic promoters. Here we show that the MACS system can successfully be transferred to a MesP1 promoter-ΔCD4 construct. After transfection into murine ES cells several stable clones were obtained in which the time course of ΔCD4-expression revealed a peak at days two and three of differentiation. Using MACS we were able to enrich this population to purities of over 97%. The MACS-positive fractions showed a strong enrichment of the endogenous murine MesP1 mRNA confirming the functionality of our construct. In reaggregation experiments after MACS we verified the viability of the sorted cells which could be further propagated in their primitive differentiation state in the presence of LIF. After LIF withdrawal subsequent spontaneous beating activity was approximately 10 fold increased. This effect is reflected by an upregulation of cardiovascular mRNAs and on the protein level (FACS) by a 3 to 10 fold increased appearance of TroponinI, α-MHC and CD31 expressing cells. The cardiomyocytes revealed normal expression patterns of sarcomeric proteins. Whole Cell Patch Clamp analyses showed action potentials characteristic for early type cardiomyocytes corresponding to embryonic hearts at ED 10. These results suggest that cardiovascular progenitor cells can be selected from ES cells via MACS purification based on MesP1 promoter driven ΔCD4 expression. These cells are predestined for cell transplantation and tissue engineering approaches.

scholarly journals Robust Cardiac Regeneration: Fulfilling the Promise of Cardiac Cell Therapy

2020 ◽  
Vol 42 (10) ◽  
pp. 1857-1879 ◽  
Author(s):  
Dinesh Selvakumar ◽  
Zoe E. Clayton ◽  
James J.H. Chong
Keyword(s):  
Cell Therapy ◽  
Cardiac Regeneration ◽  
Cardiac Cell ◽  
Cardiac Cell Therapy

scholarly journals Overcoming the Roadblocks to Cardiac Cell Therapy Using Tissue Engineering

2017 ◽  
Vol 70 (6) ◽  
pp. 766-775 ◽  
Author(s):  
Mounica Yanamandala ◽  
Wuqiang Zhu ◽  
Daniel J. Garry ◽  
Timothy J. Kamp ◽  
Joshua M. Hare ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Cell Therapy ◽  
Cardiac Cell ◽  
Cardiac Cell Therapy

scholarly journals An acute immune response underlies the benefit of cardiac adult stem cell therapy

2018 ◽  
Author(s):  
Ronald J. Vagnozzi ◽  
Marjorie Maillet ◽  
Michelle A. Sargent ◽  
Hadi Khalil ◽  
Anne Katrine Johansen ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Immune Response ◽  
Clinical Trials ◽  
Cell Therapy ◽  
Heart Function ◽  
Ischemia Reperfusion ◽  
Border Zone ◽  
Cardiac Cell ◽  
Functional Benefit ◽  
Cardiac Cell Therapy

Clinical trials using adult stem cells to regenerate damaged heart tissue continue to this day1–3 despite ongoing questions of efficacy and a lack of mechanistic understanding of the underlying biologic effect4–6. The rationale for these cell therapy trials is derived from animal studies that show a modest but reproducible improvement in cardiac function in models of cardiac ischemic injury7–9. Here we examined the mechanistic basis for cell therapy in mice after ischemia/reperfusion (I/R) injury, and while heart function was enhanced, it was not associated with new cardiomyocyte production. Cell therapy improved heart function through an acute sterile immune response characterized by the temporal and regional induction of CCR2+ and CX3CR1+ macrophages. Here we observed that intra-cardiac injection of 2 distinct types of progenitor cells, freeze/thaw-killed cells or a chemical inducer of the innate immune response similarly induced regional CCR2+ and CX3CR1+ macrophage accumulation and provided functional rejuvenation to the I/R-injured heart. Mechanistically, this selective macrophage response altered cardiac fibroblast activity and reduced border zone extracellular matrix (ECM) content and enhanced the mechanical properties of the injured area. The functional benefit of cardiac cell therapy is thus due to an acute inflammatory-based wound healing response that rejuvenates the mechanical properties of the infarcted area of the heart. Such results suggest a re-evaluation of strategies underlying cardiac cell therapy in current and planned human clinical trials.

Abstract 12613: Apurinic/apyrimidinic Endonuclease/redox Factor-1 Gene Enhances Anti-apoptotic Function of Cardiac Progenitor Cells via TAK1-Activation and Promotes Cardiac Regeneration in Myocardial Infarction

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Tatsuya Aonuma ◽  
Naofumi Takehara ◽  
Keisuke Maruyama ◽  
Maki Kabara ◽  
Motoki Matsuki ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Cell Therapy ◽  
Progenitor Cells ◽  
Culture System ◽  
Cardiac Progenitor Cells ◽  
Cardiac Cell ◽  
Cardiac Cell Therapy ◽  
Dsred Gene

Introduction: Overcoming the poor survival of cell grafts is an indispensable mission in cell therapy. Apurinic/apyrimidinic endonuclease/redox factor-1 (APE1) is known as a multifunctional enzyme to encourage cell survival, whereas the role of APE1 in cardiac cell therapy is still unknown. Hypothesis: APE1 overexpression in cardiac progenitor cells (CPC) ameliorates the effect of cardiac cell therapy. Methods: CPCs from 8-10 week-old C57BL/6 mice hearts were transfected with APE1-DsRed gene (APE1-CPC) or DsRed gene (Control [Ct]-CPC). The apoptosis induced by oxidative stress was assessed in APE1-/Ct-CPCs, and in neonatal rat cardiomyocytes (NRCM) within the co-culture system of APE1-/Ct-CPCs. Western blot analysis indicated the cellular signal to protect CPC via APE1 enzyme. To evaluate the effect of APE1 overexpression in cell therapy, we transplanted APE1-CPCs and Ct-CPCs into the mice myocardial infarction (MI) model and assessed the pathophysiological role of APE1 with functional and histological analysis. Results: Under the oxidative stress condition, APE1 overexpression inhibited the apoptosis of CPCs and accelerated TAK1 activation (Ct-CPC : APE1-CPC = 1.5±0.4 : 3.3±1.6 fold, p<0.05), and consequently NfKB phosphorylation in CPCs. In the co-culture system, the apoptosis of NRCMs was inhibited with APE1-CPCs compared to that with Ct-CPCs. In vivo, in the mice MI model, the number of total CPC grafts and cardiac α-actinin-positive graft CPCs were significantly larger in APE1-CPC injected mice (APE1 mice) compared to Ct-CPC injected mice (Ct mice) at 7 days after implantation. Eventually, the left ventricular ejection fraction of APE1 mice was significantly improved compared to Ct mice (Ct mice : APE1 mice = +3.1±6.7 : +11.3±4.0%, p<0.05) and was accompanied with the attenuation of fibrosis at 28 days after implantation. Conclusions: APE1 gene inhibited the apoptosis of CPCs and host cells against oxidative stress via the activation of TAK1-NFkB pathway, which is a novel insight into the stress response of APE1 enzyme. Furthermore, APE1-CPC grafts that effectively survived in the ischemic heart restored cardiac dysfunction and attenuated myocardial infarct size, and may be an innovative strategy to reinforce cardiac cell therapy.

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