Autologous bone marrow mononuclear cell transplantation in ischemic heart failure: A prospective, controlled, randomized, double-blind study of cell transplantation combined with coronary bypass

Pätilä, Tommi; Lehtinen, Markku; Vento, Antti; Schildt, Jukka; Sinisalo, Juha; Laine, Mika; Hämmäinen, Pekka; Nihtinen, Anne; Alitalo, Riitta; Nikkinen, Päivi; Ahonen, A; Holmström, Miia; Lauerma, Kirsi; Pöyhiä, Reino; Kupari, Markku; Kankuri, Esko; Harjula, Ari

doi:10.1016/j.healun.2014.02.009

Cited by 64 publications

(52 citation statements)

References 30 publications

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“…Research from several laboratories, including ours, suggests that stem cells hold immense potential for cardiac repair and regeneration. [1][2][3][4] Clinical use of adult stem cells is a reality today and many stem cell types, including bone marrow-derived mesenchymal stem cells (MSCs), 5 bone marrow cells, 7,8 cardiac-derived cardiac progenitor, 6 and cardio-sphere derived cells 9 have been tested. The beneficial effects of tested cell therapies on cardiac structure and function have been modest and most studies to date have not been adequately powered to document efficacy.…”

mentioning

confidence: 99%

Unique Features of Cortical Bone Stem Cells Associated With Repair of the Injured Heart

Mohsin

Troupes

Starosta

et al. 2015

Circulation Research

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Rationale: Adoptive transfer of multiple stem cell types has only had modest effects on the structure and function of failing human hearts. Despite increasing the use of stem cell therapies, consensus on the optimal stem cell type is not adequately defined. The modest cardiac repair and functional improvement in patients with cardiac disease warrants identification of a novel stem cell population that possesses properties that induce a more substantial improvement in patients with heart failure. Objective: To characterize and compare surface marker expression, proliferation, survival, migration, and differentiation capacity of cortical bone stem cells (CBSCs) relative to mesenchymal stem cells (MSCs) and cardiac-derived stem cells (CDCs), which have already been tested in early stage clinical trials. Methods and Results: CBSCs, MSCs, and CDCs were isolated from Gottingen miniswine or transgenic C57/BL6 mice expressing enhanced green fluorescent protein and were expanded in vitro. CBSCs possess a unique surface marker profile, including high expression of CD61 and integrin β4 versus CDCs and MSCs. In addition, CBSCs were morphologically distinct and showed enhanced proliferation capacity versus CDCs and MSCs. CBSCs had significantly better survival after exposure to an apoptotic stimuli when compared with MSCs. ATP and histamine induced a transient increase of intracellular Ca 2+ concentration in CBSCs versus CDCs and MSCs, which either respond to ATP or histamine only further documenting the differences between the 3 cell types. Conclusions: CBSCs are unique from CDCs and MSCs and possess enhanced proliferative, survival, and lineage commitment capacity that could account for the enhanced protective effects after cardiac injury.

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confidence: 99%

Unique Features of Cortical Bone Stem Cells Associated With Repair of the Injured Heart

Mohsin

Troupes

Starosta

et al. 2015

Circulation Research

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“…The primary outcomes of this Where multiple times of follow-up were reported, data were extracted for the longest possible duration of shortterm and long-term follow-up. The authors of 18 trials were contacted for clarification of data, including apparent discrepancies and insufficient detail in the reporting of methods or results 19,[22][23][24][25][26][27][28][29] or for mean and standard deviation values of outcomes where not explicitly reported 11,19,25,[30][31][32][33][34][35][36] or where reported graphically. 9,10,[37][38][39] Responses were obtained from authors of 7 trials (see Acknowledgments section).…”

Section: Data Extractionmentioning

confidence: 99%

“…37,42,51 Finally, 1 trial administered adipose-derived regenerative cells obtained by liposuction and followed by enzymatic digestion of the adipose tissue, cell separation, and cell elution using commercially available devices. 21 The cell dose ranged from 5×10 Fifteen trials compared cells with a placebo, 9,11,21,22,28,29,[31][32][33][34][35]42,44 generally consisting of a cell-free solution, either the participants own serum or a saline solution containing heparin. One trial used a mock injection procedure in the control arm instead of a cell-free solution.…”

Section: Characteristics Of the Included Trialsmentioning

confidence: 99%

“…In a further 14 trials, 19,24,26,28,31,32,37,42,44,48,[50][51][52][53] all outcomes mentioned in the methods were reported in the results, although it would be difficult to rule out selective reporting, and these trials were therefore considered to have an unclear risk of reporting bias. The risk of bias was also unclear in 7 other trials in which either one predefined secondary outcome was not reported, 20,34 one reported outcome was not included in the trial registration or protocol, 10,35,49 or in the case of 2 trials, 29 interim results of secondary outcomes only were presented.…”

Section: Evaluation Of Risk Of Biasmentioning

confidence: 99%

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Meta-Analysis of Cell Therapy Trials for Patients With Heart Failure

Fisher

Dorée

Mathur

et al. 2015

Circulation Research

188

158

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Rationale: Cell-based therapies are a promising intervention for the treatment of heart failure (HF) secondary to ischemic and nonischemic cardiomyopathy. However, the clinical efficacy of such new treatment requires further evaluation. Objective: To assess available clinical evidence on the safety and efficacy of cell-based therapies for HF. Methods and Results: Electronic databases (CENTRAL, DARE, NHSEED & HTA, PubMed, MEDLINE, EMBASE, CINAHL, LILACS, KoreaMed, PakMediNet, IndMed, and the Transfusion Evidence Library) were searched for relevant randomized controlled trials to June 2014. Trials of participants with HF and where the administration of any dose of autologous cells by any delivery route was compared with no intervention or placebo were eligible for inclusion. Primary outcomes were defined as mortality and rehospitalization as a result of HF. Secondary outcomes included performance status, quality of life, incidence of arrhythmias, brain natriuretic peptide levels, left ventricular ejection fraction, myocardial perfusion, and adverse events. Thirty-one independent trials (1521 participants) were included. The treatment significantly reduced the risk of mortality and rehospitalization caused by HF. There was a significant improvement in favor of stem cell treatment in performance status and exercise capacity, left ventricular ejection fraction, and quality of life. The treatment was also associated with a reduction of brain natriuretic peptide levels and no increase in the incidence of arrhythmias. However, there was considerable risk of performance, selection, and reporting bias among the included trials. Conclusions: This study shows evidence that autologous cell therapy may be beneficial for patients having HF, but further evidence is required.

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“…Recently were published the results of a large doubleblind study about the effects of intracardial injection of haematopoietic progenitor cells from bone marrow in perioperative settings in patients that have undergone cardiac bypass surgery [62]. The authors reported that the survival rates were not significantly different in the patients that have received the intracardial injection compared to the control group and that the cardiac function of the recipients was not significantly improved, albeit a reduction in the size of the myocardial scar was noted.…”

Section: Cardiomyocytes Produced By Differentiation Ofmentioning

confidence: 99%

We heart cultured hearts. A comparative review of methodologies for targeted differentiation and maintenance of cardiomyocytes derived from pluripotent and multipotent stem cells

Arabadjiev¹,

Petkova²,

Chakarov³

et al. 2014

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Citation: Arabadjiev A, Petkova R, Chakarov S, Pankov R, Zhelev N. We heart cultured hearts. A comparative review of methodologies for targeted differentiation and maintenance of cardiomyocytes derived from pluripotent and multipotent stem cells. AbstractHuman cell lines, including disease cell lines are often superior to routine animal models for the purposes of rapid and safe assessment of the effects of different agents that may modulate myocardial functioning under physiological and pathological conditions. There are several currently existing methodologies for derivation of cardiomyocyte-like cells by targeted differentiation from pluripotent cells and by reprogramming/ transdifferentiation from other types of cells (multipotent progenitors, somatic cells, etc). The present paper reviews the potential sources of cells capable of differentiation along the cardiomyocyte lineage; the existing methodologies for targeted differentiation, outlining the specificities of each method; and the markers for differentiation along the mesodermal and the cardiogenic lineage. The yield of robustly beating cells expressing cardio-specific proteins derived by any of the existing methods, however, still rarely exceeds 70-90 %, even with the newly developed approaches for increasing the differentiation capacity. There still is significant variance in the results obtained by different research groups and even between different experiments carried out in the same laboratory, with the same type of cells and same general type of protocol. Derivation of new lines of human pluripotent and multipotent stem cells according to standardised protocols and in completely defined; xeno-free conditions may increase the reliability and reproducibility of research and speed up the development of potential clinical applications.

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Autologous bone marrow mononuclear cell transplantation in ischemic heart failure: A prospective, controlled, randomized, double-blind study of cell transplantation combined with coronary bypass

Cited by 64 publications

References 30 publications

Unique Features of Cortical Bone Stem Cells Associated With Repair of the Injured Heart

Unique Features of Cortical Bone Stem Cells Associated With Repair of the Injured Heart

Meta-Analysis of Cell Therapy Trials for Patients With Heart Failure

We heart cultured hearts. A comparative review of methodologies for targeted differentiation and maintenance of cardiomyocytes derived from pluripotent and multipotent stem cells

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