Sustained release of endothelial progenitor cell-derived extracellular vesicles from shear-thinning hydrogels improves angiogenesis and promotes function after myocardial infarction

Chen, Carol W.; Wang, Leo; Zaman, Samir; Gordon, John H.; Arisi, Maria F.; Venkataraman, Chantel M.; Chung, Jennifer J.; Hung, George; Gaffey, Ann C.; Spruce, Lynn A.; Fazelinia, Hossein; Gorman, Robert C.; Seeholzer, Steven H.; Burdick, Jason A.; Atluri, Pavan

doi:10.1093/cvr/cvy067

Cited by 169 publications

(131 citation statements)

References 47 publications

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“…For applications such as bone tissue where much higher moduli are required, dECM bioinks can be combined with 3D printed porous PCL scaffolds, which can reach compressive moduli in the MPa range . In addition, there have also been efforts to develop shear‐thinning hydrogels that can flow through the needle and retain their shape after they have been printed . Such approaches may be translated into the printing of dECM to improve its printability.…”

Section: Postdecellularization Processing Methodsmentioning

confidence: 99%

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Applications of decellularized extracellular matrix in bone and cartilage tissue engineering

Kim

Majid

Melchiorri

et al. 2018

Bioengineering & Transla Med

254

175

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Regenerative therapies for bone and cartilage injuries are currently unable to replicate the complex microenvironment of native tissue. There are many tissue engineering approaches attempting to address this issue through the use of synthetic materials. Although synthetic materials can be modified to simulate the mechanical and biochemical properties of the cell microenvironment, they do not mimic in full the multitude of interactions that take place within tissue. Decellularized extracellular matrix (dECM) has been established as a biomaterial that preserves a tissue's native environment, promotes cell proliferation, and provides cues for cell differentiation. The potential of dECM as a therapeutic agent is rising, but there are many limitations of dECM restricting its use. This review discusses the recent progress in the utilization of bone and cartilage dECM through applications as scaffolds, particles, and supplementary factors in bone and cartilage tissue engineering.

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Section: Postdecellularization Processing Methodsmentioning

confidence: 99%

“…107 In addition, there have also been efforts to develop shear-thinning hydrogels that can flow through the needle and retain their shape after they have been printed. [108][109][110] Such approaches may be translated into the printing of dECM to improve its printability.…”

Section: Bioinkmentioning

confidence: 99%

Applications of decellularized extracellular matrix in bone and cartilage tissue engineering

Kim

Majid

Melchiorri

et al. 2018

Bioengineering & Transla Med

254

175

View full text Add to dashboard Cite

show abstract

“…Indeed, stimulation of cardiomyocytes undergoing Angiotensin II-induced hypertrophy and apoptosis with EPC-derived microvesicles resulted in improved survival as mediated by RNA-driven modulation of PI3K/Akt/eNOS pathway [177]. More recently, EPC-EVs have been administered to a rat model of MI within a shear-thinning hydrogel for their precise delivery and steady release, thus sustaining cardiac function and enhancing vessel density [178]. Notably, interleukin-10 deficiency within EPC-EVs has been recently shown to significantly affect their therapeutic influence for myocardial repair as altering their protein cargo and upregulating integrin-linked kinase-mediated activation of NF-κB in recipient cells; thus, modulation of the inflammatory priming of secreting EPC can impact on their EV profile and cardiovascular paracrine potential [179].…”

Section: Contribution Of Exogenous Stem/progenitor Cell-evsmentioning

confidence: 99%

Message in a Bottle: Upgrading Cardiac Repair into Rejuvenation

Balbi

Costa

Barile

2020

Cells

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Ischaemic cardiac disease is associated with a loss of cardiomyocytes and an intrinsic lack of myocardial renewal. Recent work has shown that the heart retains limited cardiomyocyte proliferation, which remains inefficient when facing pathological conditions. While broadly active in the neonatal mammalian heart, this mechanism becomes quiescent soon after birth, suggesting loss of regenerative potential with maturation into adulthood. A key question is whether this temporary regenerative window can be enhanced via appropriate stimulation and further extended. Recently the search for novel therapeutic approaches for heart disease has centred on stem cell biology. The "paracrine effect" has been proposed as a promising strategy to boost endogenous reparative and regenerative mechanisms from within the cardiac tissue by exploiting the modulatory potential of soluble stem cell-secreted factors. As such, growing interest has been specifically addressed towards stem/progenitor cell-secreted extracellular vesicles (EVs), which can be easily isolated in vitro from cell-conditioned medium. This review will provide a comprehensive overview of the current paradigm on cardiac repair and regeneration, with a specific focus on the role and mechanism(s) of paracrine action of EVs from cardiac stromal progenitors as compared to exogenous stem cells in order to discuss the optimal choice for future therapy. In addition, the challenges to overcoming translational EV biology from bench to bedside for future cardiac regenerative medicine will be discussed.

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“…Many studies have concluded that the therapeutic effects of MSCs were mainly achieved through paracrine effects and the expression of proangiogenic cytokines after transplantation. Chen et al [32] found that endothelial progenitor cell-derived extracellular vesicles injected into ischemic myocardium through injection of hydrogel could enhance the angiogenesis and myocardial hemodynamics in the infarcted rat model. Angiogenic growth factor VEGF is thought to activate every step of proangiogenic endothelial cell behavior, such as endothelial cell invasion, migration, and attachment [33].…”

Section: Discussionmentioning

confidence: 99%

IGF-1C domain–modified hydrogel enhanced the efficacy of stem cells in the treatment of AMI

et al. 2020

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Background: Due to the low survival rate of cell transplantation, stem cell has not been widely used in clinical treatment of acute myocardial infarction (AMI). In this study, we immobilized the C domain peptide of insulin-like growth factor-1 on chitosan (CS-IGF-1C) to obtain bioactive hydrogel. The purpose was to investigate whether CS-IGF-1C hydrogel incorporated with human placenta-derived mesenchymal stem cells (hP-MSCs) can boost the survival of hP-MSCs and enhance their therapeutic effects. Methods: hP-MSCs, which continuously expressed green fluorescent protein (GFP) and firefly luciferase (Fluc), were transplanted with CS-IGF-1C hydrogel into a mouse myocardial infarction model. Cell survival was detected by bioluminescence imaging (BLI), and cardiac function was measured by echocardiogram. Real-time PCR and histological analysis were used to explore the therapeutic mechanism of CS-IGF-1C hydrogel. Results: CS-IGF-1C hydrogel could induce the proliferation of hP-MSCs and exert anti-apoptotic effects in vitro. The Calcine-AM/PI staining results showed that hP-MSCs seeded on CS-IGF-1C hydrogel could protect neonatal mouse ventricular cardiomyocytes (NMVCs) against oxidative stress. It was observed by BLI that CS-IGF-1C hydrogel injected into ischemic myocardium could improve the survival rate of hP-MSCs. Histology analysis indicated that cotransplantation of the CS-IGF-1C hydrogel and hP-MSCs could increase angiogenesis, reduce collagen deposition, ameliorate left ventricular expanded, and further promote the recovery of cardiac function. Besides, we found that the inflammatory response was inhibited and the expression of apoptosis-related genes was downregulated by CS-IGF-1C hydrogel. Conclusions: CS-IGF-1C hydrogel provides a conducive microenvironment for cells and significantly boosts the survival of hP-MSCs in mouse myocardial infarction model, which suggest that it may be a potential candidate for prolonging the therapeutic effect of hP-MSCs during AMI.

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Sustained release of endothelial progenitor cell-derived extracellular vesicles from shear-thinning hydrogels improves angiogenesis and promotes function after myocardial infarction

Abstract: EPC-derived EVs delivered into ischaemic myocardium via an injectable hydrogel enhanced peri-infarct angiogenesis and myocardial haemodynamics in a rat model of MI. The STG greatly increased therapeutic efficiency and efficacy of EV-mediated myocardial preservation.

Cited by 169 publications

References 47 publications

Applications of decellularized extracellular matrix in bone and cartilage tissue engineering

Applications of decellularized extracellular matrix in bone and cartilage tissue engineering

Message in a Bottle: Upgrading Cardiac Repair into Rejuvenation

IGF-1C domain–modified hydrogel enhanced the efficacy of stem cells in the treatment of AMI

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