A stromal cell-derived factor-1 releasing matrix enhances the progenitor cell response and blood vessel growth in ischaemic skeletal muscle

Kuraitis, Drew; Zhang, P; Zhang, Y; Padavan, Donna T.; McEwan, Kimberly; Sofrenovic, Tanja; McKee, Daniel; Zhang, J; Griffith, May; Cao, Xudong; Musarò, Antonio; Ruel, Marc; Suuronen, Erik J.

doi:10.22203/ecm.v022a09

Cited by 62 publications

(39 citation statements)

References 53 publications

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“…A similar model has also shown this effect of reduced burst release effect, but using stromal cellderived factor-1-containing alginate microparticles and an injectable collagen-chondroitin sulfate hydrogel [20]. Notably, in the current study, tertiary encapsulation into a Fig.…”

Section: Discussionsupporting

confidence: 63%

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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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Section: Discussionsupporting

confidence: 63%

“…As previously described [20], blood samples (50-100μl) were procured from the saphenous veins prior-to surgery and after 1 and 2 weeks. Peripheral blood mononuclear cells were isolated using density-gradient centrifugation.…”

Section: Flow Cytometrymentioning

confidence: 99%

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

Kuraitis¹

2012

TOTERMJ

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“…PLGA microspheres in alginate hydrogels have been utilized to deliver vascular endothelial growth factor (VEGF) (Lee et al, 2010), and alginate hydrogels have been explored for delivery of hepatocyte growth factor (HGF) (Ruvinov et al, 2010), VEGF (Silva and Mooney, 2007), and pDNA encoding for VEGF (Kong et al, 2008). Alginate microspheres within an injectable collagen matrix have also been used to deliver stromal cell-derived factor-1 (SDF-1) (Kuraitis et al, 2011), while VEGF-loaded alginate microparticles in a collagen-fibronectin scaffold were used to deliver endothelial cells (Jay et al, 2008). Gelatin hydrogels have been employed to deliver basic fibroblast growth factor (bFGF) (Doi et al, 2007;Layman et al, 2007), and fibrin scaffolds were utilized to deliver bFGF and granulocyte-colony stimulating factor (G-CSF) along with bone marrow cells.…”

Section: Discussionmentioning

confidence: 99%

“…Biomaterials have also been used for delivery of growth factors or their mimics in animal models of PAD and CLI (Kawamoto et al, 2009;Layman et al, 2011;Ruvinov et al, 2010;Webber et al, 2011). However, these scaffolds are composed of fibrin (Layman et al, 2011), collagen-based matrix (Kuraitis et al, 2011), gelatin (Layman et al, 2007), self-assembling peptide amphiphiles (Webber et al, 2011) or alginate (Ruvinov et al, 2010), which may not provide the proper biomimetic environment for the ischemic skeletal muscle in these conditions. Moreover, no potential therapies employing only a biomaterial have been explored to date.…”

Section: Introductionmentioning

confidence: 99%

Injectable skeletal muscle matrix hydrogel promotes neovascularization and muscle cell infiltration in a hindlimb ischemia model

DeQuach

Lin²,

Cam³

et al. 2012

eCM

141

159

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Peripheral artery disease (PAD) currently affects approximately 27 million patients in Europe and North America, and if untreated, may progress to the stage of critical limb ischemia (CLI), which has implications for amputation and potential mortality. Unfortunately, few therapies exist for treating the ischemic skeletal muscle in these conditions. Biomaterials have been used to increase cell transplant survival as well as deliver growth factors to treat limb ischemia; however, existing materials do not mimic the native skeletal muscle microenvironment they are intended to treat. Furthermore, no therapies involving biomaterials alone have been examined. The goal of this study was to develop a clinically relevant injectable hydrogel derived from decellularized skeletal muscle extracellular matrix and examine its potential for treating PAD as a stand-alone therapy by studying the material in a rat hindlimb ischemia model. We tested the mitogenic activity of the scaffold's degradation products using an in vitro assay and measured increased proliferation rates of smooth muscle cells and skeletal myoblasts compared to collagen. In a rat hindlimb ischemia model, the femoral artery was ligated and resected, followed by injection of 150 µL of skeletal muscle matrix or collagen 1 week postinjury. We demonstrate that the skeletal muscle matrix increased arteriole and capillary density, as well as recruited more desmin-positive and MyoD-positive cells compared to collagen. Our results indicate that this tissue-specific injectable hydrogel may be a potential therapy for treating ischemia related to PAD, as well as have potential beneficial effects on restoring muscle mass that is typically lost in CLI.

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“…Another strategy to improve vascularization of implants is the inclusion of growth factors that promote angiogenesis, such as vascular endothelial growth factor [16][17][18][19] and C-X-C motif ligand 12/stromal cell-derived factor-1a (CXCL12/ SDF-1a) [20][21][22]. SDF-1a is known to be active as a potent cell-homing factor [23][24][25] through binding to its CXCR4 receptor [26] and has been proven to induce tubule formation by ECs in vitro [20,21] as well as angiogenesis in tissueengineered grafts in vivo [20,23,27].…”

Section: Introductionmentioning

confidence: 99%

CXCL12/Stromal-Cell-Derived Factor-1 Effectively Replaces Endothelial Progenitor Cells to Induce Vascularized Ectopic Bone

Eman

Hoorntje

Öner

et al. 2014

Stem Cells and Development

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Bone defect healing is highly dependent on the simultaneous stimulation of osteogenesis and vascularization. In bone regenerative strategies, combined seeding of multipotent stromal cells (MSCs) and endothelial progenitor cells (EPCs) proves their mutual stimulatory effects. Here, we investigated whether stromal-cell-derived factor1a (SDF-1a) stimulates vascularization by EPCs and whether SDF-1a could replace seeded cells in ectopic bone formation. Late EPCs of goat origin were characterized for their endothelial phenotype and showed to be responsive to SDF-1a in in vitro migration assays. Subsequently, subcutaneous implantation of Matrigel plugs that contained both EPCs and SDF-1a showed more tubule formation than constructs containing either EPCs or SDF-1a. Addition of either EPCs or SDF-1a to MSC-based constructs showed even more elaborate vascular networks after 1 week in vivo, with SDF-1a/MSC-laden groups showing more prominent interconnected networks than EPC/MSC-laden groups. The presence of abundant mouse-specific CD31/PECAM expression in these constructs confirmed ingrowth of murine vessels and discriminated between angiogenesis and vessel networks formed by seeded goat cells. Importantly, implantation of EPC/MSC or SDF-1a/MSC constructs resulted in indistinguishable ectopic bone formation. In both groups, bone onset was apparent at week 3 of implantation. Taken together, we demonstrated that SDF-1a stimulated the migration of EPCs in vitro and vascularization in vivo. Further, SDF-1a addition was as effective as EPCs in inducing the formation of vascularized ectopic bone based on MSC-seeded constructs, suggesting a cell-replacement role for SDF-1a. These results hold promise for the design of larger centimeter-scale, cell-free vascular bone grafts.

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A stromal cell-derived factor-1 releasing matrix enhances the progenitor cell response and blood vessel growth in ischaemic skeletal muscle

Cited by 62 publications

References 53 publications

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

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

Injectable skeletal muscle matrix hydrogel promotes neovascularization and muscle cell infiltration in a hindlimb ischemia model

CXCL12/Stromal-Cell-Derived Factor-1 Effectively Replaces Endothelial Progenitor Cells to Induce Vascularized Ectopic Bone

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