Cell-based interventions for therapeutic angiogenesis: review of potential cell sources

Brenes, Robert A.; Bear, Mackenzie; Jadlowiec, Caroline C.; Goodwin, Matthew D.; Hashim, Peter W.; Protack, Clinton D.; Ziegler, Kenneth R.; Li, Xin; Model, Lynn; Lv, Wei; Collins, Michael J.; Dardik, Alan

doi:10.1258/vasc.2011.201205

Cited by 20 publications

(17 citation statements)

References 85 publications

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“…CD34 is widely regarded as a marker of vascular endothelial progenitor cells 1 , 98 . These BM-derived cells are found circulating in peripheral blood 99 and their usefulness in proangiogenic therapies has been extensively researched 98 , 99 . The properties of CD34 + endothelial cells are often linked with hematopoietic cells, as both cell types can be isolated from peripheral blood using CD34 as an antigen.…”

Section: Cd34 and Endothelial Cellsmentioning

confidence: 99%

Concise Review: Evidence for CD34 as a Common Marker for Diverse Progenitors

et al. 2014

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CD34 is a transmembrane phosphoglycoprotein, first identified on hematopoietic stem and progenitor cells. Clinically, it is associated with the selection and enrichment of hematopoietic stem cells for bone marrow transplants. Due to these historical and clinical associations, CD34 expression is almost ubiquitously related to hematopoietic cells, and it is a common misconception that CD34-positive (CD34+) cells in nonhematopoietic samples represent hematopoietic contamination. The prevailing school of thought states that multipotent mesenchymal stromal cells (MSC) do not express CD34. However, strong evidence demonstrates CD34 is expressed not only by MSC but by a multitude of other nonhematopoietic cell types including muscle satellite cells, corneal keratocytes, interstitial cells, epithelial progenitors, and vascular endothelial progenitors. In many cases, the CD34+ cells represent a small proportion of the total cell population and also indicate a distinct subset of cells with enhanced progenitor activity. Herein, we explore common traits between cells that express CD34, including associated markers, morphology and differentiation potential. We endeavor to highlight key similarities between CD34+ cells, with a focus on progenitor activity. A common function of CD34 has yet to be elucidated, but by analyzing and understanding links between CD34+ cells, we hope to be able to offer an insight into the overlapping properties of cells that express CD34. Stem Cells 2014;32:1380–1389

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Section: Cd34 and Endothelial Cellsmentioning

confidence: 99%

Concise Review: Evidence for CD34 as a Common Marker for Diverse Progenitors

et al. 2014

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“…Therapeutic angiogenesis and stem cell therapies are newer treatments that may be appropriate for these difficult patients [2, 3]. However, defining optimal parameters for these gene and cell therapies is expensive to perform as clinical trials in human patients, and therefore may be more suitable in animal models [4, 5]. The murine hind limb ischemia model is a very useful model to use for testing some of these parameters and therapies [5, 6].…”

Section: Introductionmentioning

confidence: 99%

A Murine Model of Hind Limb Ischemia to Study Angiogenesis and Arteriogenesis

Dardik

2018

Methods in Molecular Biology

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Therapeutic angiogenesis offers promise as a novel treatment that is complementary to surgical or endovascular procedures for peripheral arterial diseases (PAD). Appropriate development and use of hind limb ischemia models is necessary for successful studies of therapeutic angiogenesis and/or arteriogenesis. In this chapter, we describe two commonly used murine unilateral hind limb ischemia models, the femoral artery transection model and the femoral/saphenous artery excision model.

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“…Last, we examined the effects of CCN1 and matrix culture on the properties of the CD34 + cell fraction within CACs. CD34 + cells are a highly proangiogenic subpopulation that has been used in both animal models and clinical trials to promote revascularization (5, 44). We observed that CD34 + cells from the matrix culture had increased ItgαVβ3 expression and responded to CCN1 with increased proliferation and angiogenic potential.…”

Section: Discussionmentioning

confidence: 99%

Collagen matrix‐induced expression of integrin αVβ3 in circulating angiogenic cells can be targeted by matricellular protein CCN1 to enhance their function

et al. 2014

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Circulating angiogenic cells (CACs) play an important role in vascular homeostasis and hold therapeutic promise for treating a variety of cardiovascular diseases. However, further improvements are needed because the effects of CAC therapy remain minimal or transient. The regenerative potential of these cells can be improved by culture on a collagen-based matrix through the up-regulation of key integrin proteins. We found that human CAC function was enhanced by using the matricellular protein CCN1 (CYR61/CTGF/NOV family member 1) to target integrin αV and β3, which are up-regulated on matrix. Compared to matrix-cultured CACs, CCN1-matrix CACs exhibited a 2.2-fold increase in cell proliferation, 1.8-fold greater migration toward VEGF, and 1.7-fold more incorporation into capillary-like structures in an angiogenesis assay. In vivo, intramuscular injection of CCN1-matrix-cultured CACs into ischemic hind limbs of CD-1 nude mice resulted in blood flow recovery to 80% of baseline, which was greater than matrix-cultured CACs (66%) and PBS (35%) treatment groups. Furthermore, transplanted CCN1-matrix CACs exhibited greater engraftment (11-fold) and stimulated the up-regulation of survival and angiogenic genes (>3-fold). These findings reveal the importance of cell-matrix interactions in regulating CAC function and also reveal a mechanism by which these may be exploited to enhance cell therapies for ischemic disease.

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Cell-based interventions for therapeutic angiogenesis: review of potential cell sources

Cited by 20 publications

References 85 publications

Concise Review: Evidence for CD34 as a Common Marker for Diverse Progenitors

Concise Review: Evidence for CD34 as a Common Marker for Diverse Progenitors

A Murine Model of Hind Limb Ischemia to Study Angiogenesis and Arteriogenesis

Collagen matrix‐induced expression of integrin αVβ3 in circulating angiogenic cells can be targeted by matricellular protein CCN1 to enhance their function

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