In vitro functional comparison of therapeutically relevant human vasculogenic progenitor cells used for cardiac cell therapy

Zhang, Yan; Wong, Serena; Lafleche, Jessica; Crowe, Suzanne; Mesana, Thierry G.; Suuronen, Erik J.; Ruel, Marc

doi:10.1016/j.jtcvs.2009.11.016

Cited by 14 publications

(10 citation statements)

References 24 publications

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“…Skeletal myogenesis was also less enhanced in the CB‐CD34 + cell postexpansion group than in the pre‐expansion group [5]. Other groups have also developed growth factor cocktails to test EPC expansions from CB‐CD34 + or CD133 + cell populations and demonstrated significant increases in total cell number and EPC marker‐positive cell number [25, 41]. All studies demonstrated the efficacy of transplantation into myocardial ischemic models by the equivalent or better improvement of cardiac function or vascular incorporation compared with pre‐expansion EPCs.…”

Section: Discussionmentioning

confidence: 99%

Development of Serum-Free Quality and Quantity Control Culture of Colony-Forming Endothelial Progenitor Cell for Vasculogenesis

Masuda

Iwasaki

Kawamoto

et al. 2012

Stem Cells Translational Medicine

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Quantitative and qualitative impairment of endothelial progenitor cells (EPCs) limits the efficacy of autologous cell therapy in patients with cardiovascular diseases. Here, we developed a serum-free quality and quantity control culture system for colony-forming EPCs to enhance their regenerative potential. A culture with serum-free medium containing stem cell factor, thrombopoietin, vascular endothelial growth factor, interleukin-6, and Flt-3 ligand was determined as optimal quality and quantity culture ( MEDICINE 2012;1:160 -171

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Section: Discussionmentioning

confidence: 99%

Development of Serum-Free Quality and Quantity Control Culture of Colony-Forming Endothelial Progenitor Cell for Vasculogenesis

Masuda

Iwasaki

Kawamoto

et al. 2012

Stem Cells Translational Medicine

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“…CD133 + cells in vitro differentiate into endothelial cells and release paracrine angiogenic cytokines. Differentiated CD133 + are capable of inducing capillary tubes in vitro [46,48-51] and several clinical trials have reported promising effects following infusion or direct intramyocardial injection of autologous CD133 + cells into ischemic hearts[52-56]. …”

Section: Hematopoietic and Endothelial Precursor Stem Cellsmentioning

confidence: 99%

Optimizing stem cells for cardiac repair: Current status and new frontiers in regenerative cardiology

Sarkissian¹,

Lévesque²,

Noiseux³

2017

WJSC

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Cell therapy has the potential to improve healing of ischemic heart, repopulate injured myocardium and restore cardiac function. The tremendous hope and potential of stem cell therapy is well understood, yet recent trials involving cell therapy for cardiovascular diseases have yielded mixed results with inconsistent data thereby readdressing controversies and unresolved questions regarding stem cell efficacy for ischemic cardiac disease treatment. These controversies are believed to arise by the lack of uniformity of the clinical trial methodologies, uncertainty regarding the underlying reparative mechanisms of stem cells, questions concerning the most appropriate cell population to use, the proper delivery method and timing in relation to the moment of infarction, as well as the poor stem cell survival and engraftment especially in a diseased microenvironment which is collectively acknowledged as a major hindrance to any form of cell therapy. Indeed, the microenvironment of the failing heart exhibits pathological hypoxic, oxidative and inflammatory stressors impairing the survival of transplanted cells. Therefore, in order to observe any significant therapeutic benefit there is a need to increase resilience of stem cells to death in the transplant microenvironment while preserving or better yet improving their reparative functionality. Although stem cell differentiation into cardiomyocytes has been observed in some instance, the prevailing reparative benefits are afforded through paracrine mechanisms that promote angiogenesis, cell survival, transdifferentiate host cells and modulate immune responses. Therefore, to maximize their reparative functionality, ex vivo manipulation of stem cells through physical, genetic and pharmacological means have shown promise to enable cells to thrive in the post-ischemic transplant microenvironment. In the present work, we will overview the current status of stem cell therapy for ischemic heart disease, discuss the most recurring cell populations employed, the mechanisms by which stem cells deliver a therapeutic benefit and strategies that have been used to optimize and increase survival and functionality of stem cells including ex vivo preconditioning with drugs and a novel “pharmaco-optimizer” as well as genetic modifications.

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“…However, the challenge of stimulating coronary collateral growth is far less involved, and is a strategy more likely to produce an immediate benefit in the treatment of ischemic heart disease. 6, 7 “Ideal” stem/iPS/progenitor cell population for optimal coronary collateral growth (also termed arteriogenesis and collaterogenesis) in ischemic myocardium has not been identified. 6, 8 Many cell types, such as endothelial progenitor cells from blood or bone marrow, cardiac progenitor cells from the heart, mesenchymal stem cells from bone marrow and others, are currently being examined as cell sources for cardiovascular regenerative cell therapy.…”

Section: Introductionmentioning

confidence: 99%

Induction of Vascular Progenitor Cells From Endothelial Cells Stimulates Coronary Collateral Growth

Yin

Ohanyan

Pung

et al. 2012

Circulation Research

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Rationale A well-developed coronary collateral circulation improves the morbidity and mortality of patients following an acute coronary occlusion. Although regenerative medicine has great potential in stimulating vascular growth in the heart, to date there have been mixed results, and the ideal cell type for this therapy has not been resolved. Objective To generate induced vascular progenitor cell(s) (iVPC(s)) from endothelial cells, which can differentiate into vascular smooth muscle cells (VSMC(s)) or endothelial cells (EC(s)), and test their capability to stimulate coronary collateral growth. Methods and Results We reprogrammed rat ECs with the transcription factors Oct4, Klf4, Sox2 and c-Myc. A population of reprogrammed cells was derived which expressed pluripotent markers Oct4, SSEA-1, Rex1 and AP and hemangioblast markers CD133, Flk1, and c-kit. These cells were designated iVPCs because they remained committed to vascular lineage and could differentiate into vascular ECs and VSMCs in vitro. The iVPCs demonstrated better in vitro angiogenic potential (tube network on 2D culture, tube formation in growth factor reduced Matrigel) than native ECs. The risk of teratoma formation in iVPCs is also reduced compared to fully reprogrammed induced pluripotent stem cell(s) (iPSC(s)). When iVPCs were implanted into myocardium, they engrafted into blood vessels and increased coronary collateral flow (microspheres) and improved cardiac function (echocardiography) better than iPSCs, mesenchymal stem cells, native ECs and sham treatments. Conclusions We conclude that iVPCs, generated by partially reprogramming ECs, are an ideal cell type for cell-based therapy designed to stimulate coronary collateral growth.

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In vitro functional comparison of therapeutically relevant human vasculogenic progenitor cells used for cardiac cell therapy

Cited by 14 publications

References 24 publications

Development of Serum-Free Quality and Quantity Control Culture of Colony-Forming Endothelial Progenitor Cell for Vasculogenesis

Development of Serum-Free Quality and Quantity Control Culture of Colony-Forming Endothelial Progenitor Cell for Vasculogenesis

Optimizing stem cells for cardiac repair: Current status and new frontiers in regenerative cardiology

Induction of Vascular Progenitor Cells From Endothelial Cells Stimulates Coronary Collateral Growth

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