Phases I–III Clinical Trials Using Adult Stem Cells

Sanz‐Ruiz, Ricardo; Ibañes, Enrique Gutiérrez; Arranz, Adolfo Villa; Santos, María Eugenia Fernández; Fernández, Pedro; Fernández‐Avilés, Francisco

doi:10.4061/2010/579142

Cited by 42 publications

(38 citation statements)

References 46 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While successful stem cell interventions have been obtained using animal models [17,[79][80][81], as well as promising results in clinical trials on cardiac patients [82][83][84], the outcomes from these studies has not always been repeatable and has often been rather modest in effect [85,86]. It is not yet clear what the best sources are of stem cells for cardiac repair, and whether these various stem cell populations have been optimized in their cardiac capacity.…”

Section: Discussionmentioning

confidence: 99%

The Histone Methyltransferase Inhibitor BIX01294 Enhances the Cardiac Potential of Bone Marrow Cells

Mezentseva

Yang²,

Kaur³

et al. 2013

Stem Cells and Development

View full text Add to dashboard Cite

Bone marrow (BM) has long been considered a potential stem cell source for cardiac repair due to its abundance and accessibility. Although previous investigations have generated cardiomyocytes from BM, yields have been low, and far less than produced from ES or induced pluripotent stem cells (iPSCs). Since differentiation of pluripotent cells is difficult to control, we investigated whether BM cardiac competency could be enhanced without making cells pluripotent. From screens of various molecules that have been shown to assist iPSC production or maintain the ES cell phenotype, we identified the G9a histone methyltransferase inhibitor BIX01294 as a potential reprogramming agent for converting BM cells to a cardiac-competent phenotype. BM cells exposed to BIX01294 displayed significantly elevated expression of brachyury, Mesp1, and islet1, which are genes associated with embryonic cardiac progenitors. In contrast, BIX01294 treatment minimally affected ectodermal, endodermal, and pluripotency gene expression by BM cells. Expression of cardiac-associated genes Nkx2.5, GATA4, Hand1, Hand2, Tbx5, myocardin, and titin was enhanced 114,76, 276,46, 635, 123, and 5-fold in response to the cardiogenic stimulator Wnt11 when BM cells were pretreated with BIX01294. Immunofluorescent analysis demonstrated that BIX01294 exposure allowed for the subsequent display of various muscle proteins within the cells. The effect of BIX01294 on the BM cell phenotype and differentiation potential corresponded to an overall decrease in methylation of histone H3 at lysine9, which is the primary target of G9a histone methyltransferase. In summary, these data suggest that BIX01294 inhibition of chromatin methylation reprograms BM cells to a cardiac-competent progenitor phenotype.

show abstract

Section: Discussionmentioning

confidence: 99%

The Histone Methyltransferase Inhibitor BIX01294 Enhances the Cardiac Potential of Bone Marrow Cells

Mezentseva

Yang²,

Kaur³

et al. 2013

Stem Cells and Development

View full text Add to dashboard Cite

show abstract

“…In clinical trials, methods to measure cardiac function include echocardiography, SPECT and MRI (Hare et al ., 2009;George, 2010;Sanz-Ruiz et al ., 2010). As LVEF is the most frequently used parameter, techniques of choice to quantify LVEF in SC clinical trials are MRI, SPECT and contrast-enhanced echocardiography.…”

Section: Evaluation Of Heart Functionmentioning

confidence: 95%

Cardiac cell therapy: current status and future trends

Wang

Wei

et al. 2014

Cardiac Regeneration and Repair

View full text Add to dashboard Cite

“…In clinical trials, methods to measure cardiac function include echocardiography, single photon emission computed tomography, and magnetic resonance imaging (MRI) 1,3,37,147–149. These methods are well established, but more sensitive methods are necessary to evaluate SC homing and engraftment.…”

Section: Assessment Of Sc Therapymentioning

confidence: 99%

Challenges for heart disease stem cell therapy

Hoover‐Plow¹,

Gong²

2012

VHRM

View full text Add to dashboard Cite

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. The use of stem cells to improve recovery of the injured heart after myocardial infarction (MI) is an important emerging therapeutic strategy. However, recent reviews of clinical trials of stem cell therapy for MI and ischemic heart disease recovery report that less than half of the trials found only small improvements in cardiac function. In clinical trials, bone marrow, peripheral blood, or umbilical cord blood cells were used as the source of stem cells delivered by intracoronary infusion. Some trials administered only a stem cell mobilizing agent that recruits endogenous sources of stem cells. Important challenges to improve the effectiveness of stem cell therapy for CVD include: (1) improved identification, recruitment, and expansion of autologous stem cells; (2) identification of mobilizing and homing agents that increase recruitment; and (3) development of strategies to improve stem cell survival and engraftment of both endogenous and exogenous sources of stem cells. This review is an overview of stem cell therapy for CVD and discusses the challenges these three areas present for maximum optimization of the efficacy of stem cell therapy for heart disease, and new strategies in progress.

show abstract

Phases I–III Clinical Trials Using Adult Stem Cells

Cited by 42 publications

References 46 publications

The Histone Methyltransferase Inhibitor BIX01294 Enhances the Cardiac Potential of Bone Marrow Cells

The Histone Methyltransferase Inhibitor BIX01294 Enhances the Cardiac Potential of Bone Marrow Cells

Cardiac cell therapy: current status and future trends

Challenges for heart disease stem cell therapy

Contact Info

Product

Resources

About