Ex vivo generation of a highly potent population of circulating angiogenic cells using a collagen matrix

Kuraitis, Drew; Hou, Chenchen; Zhang, Yan; Vulesevic, Branka; Sofrenovic, Tanja; McKee, Daniel; Sharif, Zahra; Ruel, Marc; Suuronen, Erik J.

doi:10.1016/j.yjmcc.2011.04.011

Cited by 43 publications

(31 citation statements)

References 44 publications

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“…14 We also previously showed that CACs exposed to the matrix demonstrated higher levels of phosphorylated Akt (PI3K/Akt pathway) and increased survival under hypoxia. 15 Based on the ability of the collagen matrix to modulate the therapeutic phenotype and function of CACs, it may have induced similar effects in the pig model of this study. The increased retention and viability of cells within the matrix may also have provided more prolonged paracrine effects because transplanted cells secrete proangiogenic factors 37 and upregulate host-derived cytokine secretion.…”

Section: Discussionmentioning

confidence: 84%

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Preclinical Evaluation of Biopolymer-Delivered Circulating Angiogenic Cells in a Swine Model of Hibernating Myocardium

Giordano

Thorn

Renaud

et al. 2013

Circ: Cardiovascular Imaging

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M yocardial hibernation is a common clinical condition affecting patients with advanced coronary artery disease, 1 for whom cell-based therapies are targeted. In hibernation, repetitive episodes of ischemia and reperfusion lead to metabolic and functional changes in cardiomyocytes, ultimately impairing left ventricular (LV) function. Current therapies such as coronary artery bypass grafting or percutaneous coronary intervention are well established but not suitable for all patients; in previous clinical research from our group, more than one third of patients referred for revascularization did not undergo intervention because of unsuitable vessel anatomy, comorbidities, or other reasons.1 These patients are at high risk of cardiac events, and novel approaches such as cell-based vasculogenic therapy could provide them with an alternative form of therapy. Clinical Perspective on p 991Circulating angiogenic cells (CACs) constitute a heterogeneous population of peripheral blood-derived fibronectincultured cells. Although what defines their phenotype is still debated, 2 they were shown to uptake acetylated low-density lipoprotein, bind Ulex europaeus agglutinin-1 lectin, and express the pan-leukocyte marker CD45. They can also stain positive for monocyte/macrophage (CD14, CD11b/Mac-1, and CD11c) and endothelial (vascular endothelial growth factor receptor 2, von Willebrand factor, vascular endothelialcadherin, and CD31) markers. [3][4][5] Transplanted cells likely contribute to neovascularization through a paracrine mechanism by secreting and recruiting cardioprotective or proangiogenic growth factors. 6,7 The revascularization potential of Background-Vasculogenic cell-based therapy combined with tissue engineering is a promising revascularization approach targeted at patients with advanced coronary artery disease, many of whom exhibit myocardial hibernation. However, to date, no experimental data have been available in this context; we therefore examined the biopolymer-supported delivery of circulating angiogenic cells using a clinically relevant swine model of hibernating myocardium. Methods and Results-Twenty-five swine underwent placement of an ameroid constrictor on the left circumflex artery.After 2 weeks, animals underwent echocardiography, rest and stress ammonia-positron emission tomography perfusion, and fluorodeoxyglucose positron emission tomography viability scans. The following week, swine were randomized to receive intramyocardial injections of PBS control (n=10), circulating angiogenic cells (n=8), or circulating angiogenic cells+collagen-based matrix (n=7). The imaging protocol was repeated after 7 weeks. Baseline positron emission tomography myocardial blood flow and myocardial flow reserve were reduced in the left circumflex artery territory (both P<0.001), and hibernation (mismatch) was observed. At follow-up, stress myocardial blood flow had increased (P≤0.01) and hibernation decreased (P<0.01) in the cells+matrix group only. Microsphere-measured myocardial blood flow validated the perfusion resu...

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Section: Discussionmentioning

confidence: 84%

“…15 Briefly, components were mixed on ice and cross-linked with glutaraldehyde (1.5%). Residual aldehyde groups were inactivated by the addition of glycine (20%).…”

Section: Collagen Matrix Preparationmentioning

confidence: 99%

Preclinical Evaluation of Biopolymer-Delivered Circulating Angiogenic Cells in a Swine Model of Hibernating Myocardium

Giordano

Thorn

Renaud

et al. 2013

Circ: Cardiovascular Imaging

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“…Indeed, in the development of new biomaterials by combining different molecular components at tailored concentrations and geometries, a wide range of tissue-unique structural requirements can be met [276]. Along with recent advances in ECM science and developmental biology, concentrated efforts on the exploration of human-derived biomaterials for therapeutics have now moved from the direct use of autogenic tissue grafts, allogenic tissues/organs from donors and a wide variety of allografts from cadavers toward the recreation of human-derived extracellular influences in simplified forms, the decellularization of tissues and organs for scaffolding use and the incorporation of short functional domains derived from human tissue into ECM-mimicking biomaterials to manipulate cell fate commitment [52,289,290]. …”

Section: Human Tissue Ecm-based Biomaterialsmentioning

confidence: 99%

Advancing biomaterials of human origin for tissue engineering

Chen

Liu

2016

Progress in Polymer Science

921

513

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Biomaterials have played an increasingly prominent role in the success of biomedical devices and in the development of tissue engineering, which seeks to unlock the regenerative potential innate to human tissues/organs in a state of deterioration and to restore or reestablish normal bodily function. Advances in our understanding of regenerative biomaterials and their roles in new tissue formation can potentially open a new frontier in the fast-growing field of regenerative medicine. Taking inspiration from the role and multi-component construction of native extracellular matrices (ECMs) for cell accommodation, the synthetic biomaterials produced today routinely incorporate biologically active components to define an artificial in vivo milieu with complex and dynamic interactions that foster and regulate stem cells, similar to the events occurring in a natural cellular microenvironment. The range and degree of biomaterial sophistication have also dramatically increased as more knowledge has accumulated through materials science, matrix biology and tissue engineering. However, achieving clinical translation and commercial success requires regenerative biomaterials to be not only efficacious and safe but also cost-effective and convenient for use and production. Utilizing biomaterials of human origin as building blocks for therapeutic purposes has provided a facilitated approach that closely mimics the critical aspects of natural tissue with regard to its physical and chemical properties for the orchestration of wound healing and tissue regeneration. In addition to directly using tissue transfers and transplants for repair, new applications of human-derived biomaterials are now focusing on the use of naturally occurring biomacromolecules, decellularized ECM scaffolds and autologous preparations rich in growth factors/non-expanded stem cells to either target acceleration/magnification of the body's own repair capacity or use nature's paradigms to create new tissues for restoration. In particular, there is increasing interest in separating ECMs into simplified functional domains and/or biopolymeric assemblies so that these components/constituents can be discretely exploited and manipulated for the production of bioscaffolds and new biomimetic biomaterials. Here, following an overview of tissue auto-/allo-transplantation, we discuss the recent trends and advances as well as the challenges and future directions in the evolution and application of human-derived biomaterials for reconstructive surgery and tissue engineering. In particular, we focus on an exploration of the structural, mechanical, biochemical and biological information present in native human tissue for bioengineering applications and to provide inspiration for the design of future biomaterials.

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“…Animals receiving FGF-2 treatment demonstrated higher levels of therapeutic cell-mobilizing cytokines G-CSF, MCP-1 and VEGF. Other studies have correlated enhanced angiogenesis in animal models with increased levels of G-CSF [30], MCP-1 [19,31] and VEGF [30]. Based on the serum cytokine profile observed, it may prove to be that another effect of our FGF-2 delivery system is to induce a systemic environment that is supportive of angiogenesis.…”

Section: Fig (5)mentioning

confidence: 81%

Tertiary Biomaterial Encapsulation Controls the Release of FGF-2 without Impacting Bioactivity

Kuraitis¹

2012

TOTERMJ

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Diseases that restrict the flow of blood to muscles in the peripheral limbs or the heart remain prevalent causes of reduced quality of life and death in developed countries. Signaling molecules that play a role in the regenerative responses are currently being exploited as potential therapies to restore blood flow and tissue function. Fibroblast growth factor-2 (FGF-2) is a potent stimulator of neovascularization. It is believed that a controlled release of a delivered cytokine is superior to a bolus administration for achieving the desired regenerative effect. Therefore, we incorporated FGF-2-containing microspheres into a hydrogel and further encased this hydrogel into a collagen capsule for implantation. Cytokine release was controlled and constant over a month-long study period, and FGF-2 released from this tertiary encapsulation system maintained its bioactivity, as measured by its proliferative effects on endothelium. In a subcutaneous mouse model, FGF-2 treatment induced a systemic response that included increased stem cell chemoattractant cytokines, the mobilization of a potent CXCR4 + angiogenic population, and also an increase in the density of small diameter blood vessels. These observations were accompanied by no changes in the systemic levels of inflammatory cytokines. Overall, tertiary encapsulation of FGF-2 retards its release and allows for a more controlled and constant delivery of FGF-2, while maintaining its bioactive effects on endothelial cells and systemic responses in vivo.

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Ex vivo generation of a highly potent population of circulating angiogenic cells using a collagen matrix

Cited by 43 publications

References 44 publications

Preclinical Evaluation of Biopolymer-Delivered Circulating Angiogenic Cells in a Swine Model of Hibernating Myocardium

Preclinical Evaluation of Biopolymer-Delivered Circulating Angiogenic Cells in a Swine Model of Hibernating Myocardium

Advancing biomaterials of human origin for tissue engineering

Tertiary Biomaterial Encapsulation Controls the Release of FGF-2 without Impacting Bioactivity

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