CD34-Positive Cells Exhibit Increased Potency and Safety for Therapeutic Neovascularization After Myocardial Infarction Compared With Total Mononuclear Cells

Kawamoto, Atsuhiko; Iwasaki, Hiroto; Kusano, Kengo; Murayama, Toshinori; Oyamada, Akira; Silver, Marcy; Hulbert, Christine; Gavin, Mary; Hanley, Allison; Ma, Hong; Kearney, Marianne; Zak, Victor; Asahara, Takayuki; Losordo, Douglas W.

doi:10.1161/circulationaha.106.644518

Cited by 324 publications

(254 citation statements)

References 25 publications

(17 reference statements)

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“…Circulating human CD34 + cells also contain a small fraction of endothelial progenitor cells (EPC) [33]. A previous investigation [22] has suggested a therapeutic potential of highly purified CD34 + EPCs, derived from circulating mononuclear cells, in the treatment of cardiac infarcts. A low frequency of murine bone marrow CD34…”

Section: Discussionmentioning

confidence: 99%

“…+ cells have been shown to exhibit EPC characteristics [34], and EPC are known to have proangiogenic effects which can positively affect the outcome of ischemia [22].…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have suggested that stem cell samples used to treat myocardial infarction promote neo-vascularization, and that this may be responsible for the regenerative effects of these treatments [21,22,31,32]. To determine more conclusively whether HSC are responsible for this revascularization following bone marrow cell treatment, we analyzed the density of capillaries in the peri-infarct zone of infarcted hearts one month after treatment (Figure 5(a)).…”

Section: Analysis Of the Relative Contribution Of Hsc To Facilitationmentioning

confidence: 99%

“…Mobilization of BM stem cells either as a natural response to injury [19] or with granulocyte colony-stimulating factor [20] show functional improvements, albeit limited, which may be linked to improved perfusion of the infarcted area. Mobilized CD34 + cells have been shown to contribute to vasculogenesis and cardiomyogenesis in rats [21], and have also been shown to have greater efficacy than total mononuclear cells [22]. Autologous CD34 + cells infused into the infarcted artery of acute MI patients in human trials showed a similar positive response to the findings in rat models [23], although this was not carried out in direct comparison to the total BM cell population.…”

Section: Introductionmentioning

confidence: 98%

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Hematopoietic stem cells are a critical sub-population of whole bone marrow in the treatment of myocardial infarction

Davy¹,

Walker²,

Wong³

et al. 2013

SCD

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Recent studies suggest that whole bone marrow (WBM) derived stem cells may facilitate recovery following myocardial infarction. However, the sub-population of WBM responsible for recovery remains uncertain. By adjusting the abundance of CD34 + LinNeg cells in human bone marrow we examined the relative significance of hematopoietic stem cells (HSC) in the recovery of cardiac function in a murine model of induced myocardial infarction. Enrichment of HSC by ~100-fold in WBM transplanted into mice significantly increased recovery of heart function and reduced scar size compared to transplantation of WBM depleted in HSC by ~10-fold (P < 0.05, and P < 0.01 respectively). Peri-infarct capillary density was significantly increased in recipients of HSC-enriched samples (P < 0.01) or WBM samples (P < 0.01) compared to controls. These results strongly suggest a critical role for HSC in the effective treatment of myocardial infarction with human bone marrow, and imply that enrichment of HSC may markedly benefit the clinical application of WBM treatments.

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Section: Discussionmentioning

confidence: 99%

“…+ cells have been shown to exhibit EPC characteristics [34], and EPC are known to have proangiogenic effects which can positively affect the outcome of ischemia [22].…”

Section: Discussionmentioning

confidence: 99%

Section: Analysis Of the Relative Contribution Of Hsc To Facilitationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

Hematopoietic stem cells are a critical sub-population of whole bone marrow in the treatment of myocardial infarction

Davy¹,

Walker²,

Wong³

et al. 2013

SCD

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show abstract

“…Both vasculogenesis and angiogenesis occur during embryonic development (Asahara & Kawamoto 2004;Kawamoto et al 2006). EPCs are a subtype of stem cells with high proliferative potential that are capable of differentiating into mature ECs and contributing to neovascularization (Yoder 2012).…”

Section: Introductionmentioning

confidence: 99%

Angiogenic activity of endothelial progenitor cells through angiopoietin-1 and angiopoietin-2

Siavashi

Sariri

Nassiri

et al. 2016

Animal Cells and Systems

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Angiogenesis is a regulated process involving the proliferation, migration, and remodeling of different cell types particularly mature endothelial cells and recently discovered progenitor cells, named as endothelial progenitor cells (EPCs). Up to now, many attempts have been made to understand the dynamic balance of pro-and anti-angiogenic factors on EPCs on different milieu. It has been accepted that Ang-1, -2 and Tie-1, -2 signaling play a key role on angiogenesis pathways in endothelial lineage cells. In the current experiment, the angiogenic/angiomodulatory potency of Ang-1 and -2 was investigated on isolated EPCs. Freshly isolated EPCs were exposed to different concentrations of Ang-1 and -2 (25 and 50 ng/ml) over a course of 7 and 14 days. Corroborating to our results, a superior effect of Ang-1 on angiogenic properties, including an increased concentration of vascular endothelial growth factor, in vitro tubulogenesis, EPC migratory, Tie-2 expression and clonogenicity, was determined. A large amount of positive mature endothelium markers was achieved in EPCs being-exposed to Ang-1 peptide. Nonetheless, the number of CD133 positive cells increased in the presence of Ang-2. Collectively, we conclude that Ang-1 potentially induces functional and mature vascular-like behavior in EPCs more than Ang-2.ARTICLE HISTORY

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Endothelial progenitor cell therapy for the treatment of coronary disease, acute MI, and pulmonary arterial hypertension: Current perspectives

Ward

Stewart

Kutryk

2007

Cathet Cardio Intervent

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Since their identification in 1997, bone marrow derived endothelial progenitor cells (EPCs) have been studied for their role in the endogenous maintenance and repair of endothelium and their potential regenerative capacity beyond the endothelium. In particular, EPCs have been tested in cell therapy approaches with the aim of developing novel therapies for conditions currently lacking effective treatment options. In this review, we discuss the scientific background and clinical experience using EPC delivery or mobilization for the treatment of post-angioplasty restenosis, acute myocardial infarction and pulmonary arterial hypertension. Although these approaches are safe, efficacy has yet to be proven in large randomized clinical trials. Unfortunately, the biology of EPCs is still poorly understood. The success of future clinical trials depends on a better understanding of EPC biology and intelligent design.

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CD34-Positive Cells Exhibit Increased Potency and Safety for Therapeutic Neovascularization After Myocardial Infarction Compared With Total Mononuclear Cells

Cited by 324 publications

References 25 publications

Hematopoietic stem cells are a critical sub-population of whole bone marrow in the treatment of myocardial infarction

Hematopoietic stem cells are a critical sub-population of whole bone marrow in the treatment of myocardial infarction

Angiogenic activity of endothelial progenitor cells through angiopoietin-1 and angiopoietin-2

Endothelial progenitor cell therapy for the treatment of coronary disease, acute MI, and pulmonary arterial hypertension: Current perspectives

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