Human umbilical cord mesenchymal stem cell derived exosomes encapsulated in functional peptide hydrogels promote cardiac repair

Han, Chaoshan; Zhou, Jin; Liang, Chun; Liu, Bin; Pan, Xiangbin; Zhang, Yu; Wang, Yanli; Yan, Bing; Xie, Wenping; Liu, Feng; Yu, Xiyong; Li, Yangxin

doi:10.1039/c9bm00101h

Cited by 191 publications

(142 citation statements)

References 51 publications

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“…[ 216 ] EV‐laden peptide hydrogels showed superior therapeutic performance compared to bolus EV injection in a rat MI model, in terms of increasing angiogenesis, and reducing fibrosis, apoptosis, and inflammation. [ 57 ] Similarly, intramyocardially injected EVs entrapped in an alginate hydrogel showed improved retention in the heart and enhanced reparative potency compared with bolus EV injections in a rat MI model. [ 202 ] Finally, in a rat model of hyperlipidemia, MSC‐EVs loaded onto a PCL vascular graft promoted vascular regeneration, likely by immunomodulation as M1 to M2 macrophage polarization was observed both in vitro and in vivo.…”

Section: Biomaterials Functionalized With Msc Secretomementioning

confidence: 99%

Biomaterials Functionalized with MSC Secreted Extracellular Vesicles and Soluble Factors for Tissue Regeneration

Brennan

Layrolle

Mooney

2020

Adv Funct Materials

216

174

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The therapeutic benefits of mesenchymal stromal cell (MSC) transplantation are attributed to their secreted factors, including extracellular vesicles (EVs) and soluble factors. The potential of employing the MSC secretome as an alternative acellular approach to cell therapy is being investigated in various tissue injury indications, but EVs administered via bolus injections are rapidly sequestered and cleared. However, biomaterials offer delivery platforms to enhance EV retention rates and healing efficacy. This review highlights the mechanisms underpinning the therapeutic effects of MSC‐EVs and soluble factors as effectors of immunomodulation and tissue regeneration, conferred primarily via their nucleic acid and protein contents. Discussed is how manipulating the cell culture microenvironment or genetic modification of MSCs can further augment the potency of their secretions. The most recent advances in the development of EV‐functionalized biomaterials that mediate enhanced angiogenesis and cell survival, while attenuating inflammation and fibrosis, are presented. Finally, some technical challenges to be considered for the clinical translation of biomaterials carrying MSC‐secreted bioactive cargo are discussed.

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Section: Biomaterials Functionalized With Msc Secretomementioning

confidence: 99%

Biomaterials Functionalized with MSC Secreted Extracellular Vesicles and Soluble Factors for Tissue Regeneration

Brennan

Layrolle

Mooney

2020

Adv Funct Materials

216

174

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“…RADA16‐I peptide modified with QHREDGS, an prosurvival peptide derived from angiopoeitin‐1, is a novel delivery system of exosome‐mediated miR‐21 for progenitor stem cell transplantation, [ 85 ] which reduce scar size and cell apoptosis and improve cardiac function. Due to the nonimmunogenic nature of designer peptide amphiphile, cardiac protective peptides (GHRPS) and matrix metalloprotease‐2 (MMP‐2) sequence (GTAGLIGQ) are incorporated into a designer C16 peptide to form the functionalized peptide hydrogels, [ 186 ] which maintain a stable and sustained release of exosomes. So, chemically synthetic designer peptide hydrogels can increase the stability of exosomes and effectively prevent from H 2 O 2 ‐induced oxidative stress.…”

Section: Instructive Cell Constructs In Tissue Engineering and Precismentioning

confidence: 99%

Designer Self‐Assembling Peptide Hydrogels to Engineer 3D Cell Microenvironments for Cell Constructs Formation and Precise Oncology Remodeling in Ovarian Cancer

Yang

Zhao

2020

Advanced Science

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mouse intestinal stem cells and primary colorectal cancer cells can be propagated in vitro long term, [1] there is an urgent need to develop more physiologically relevant, efficient, and robust precise oncology models that closely recapitulate the genetic and morphological heterogeneous composition and mimic the arrangement pattern of cancer cells in the original tumor. [2] To our knowledge in biomedical research, hydrogel is the best tool to reconstruct precise oncology models in vitro, especially tumor organoid, which not only recapitulates in vivo biology and microenvironmental factors, but also at large extent allows side-by-side comparison to evaluate the translational potential of 3D model systems to the patients. [2a,3] Generally, hydrogels are mainly composed of hydrophilic polymeric scaffolds that absorb large amounts of water, so the hydrogel matrix better mimics elastic and viscoelastic properties in ECM and microscale topographies of cell matrices, which controls proper cell morphology, directs viable cell behaviors, and drives in vivo fundamental cell-cell or cell-ECM interactions. [4] To recapitulate pathophysiological features of human tumors and imitate various aspects of human tumorigenesis in vivo, hydrogels can provide a realistic platform to establish a useful bridge between in vitro assays and in vivo cell microenvironments. In current biomedical applications, there are many kinds of hydrogels to be developed to mimic the biological properties of ECM, such Designer self-assembling peptides form the entangled nanofiber networks in hydrogels by ionic-complementary self-assembly. This type of hydrogel has realistic biological and physiochemical properties to serve as biomimetic extracellular matrix (ECM) for biomedical applications. The advantages and benefits are distinct from natural hydrogels and other synthetic or semisynthetic hydrogels. Designer peptides provide diverse alternatives of main building blocks to form various functional nanostructures. The entangled nanofiber networks permit essential compositional complexity and heterogeneity of engineering cell microenvironments in comparison with other hydrogels, which may reconstruct the tumor microenvironments (TMEs) in 3D cell cultures and tissue-specific modeling in vitro. Either ovarian cancer progression or recurrence and relapse are involved in the multifaceted TMEs in addition to mesothelial cells, fibroblasts, endothelial cells, pericytes, immune cells, adipocytes, and the ECM. Based on the progress in common hydrogel products, this work focuses on the diverse designer self-assembling peptide hydrogels for instructive cell constructs in tissue-specific modeling and the precise oncology remodeling for ovarian cancer, which are issued by several research aspects in a 3D context. The advantages and significance of designer peptide hydrogels are discussed, and some common approaches and coming challenges are also addressed in current complex tumor diseases.

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“…Exosomes, extracellular vesicles derived from endosomes and the vital mediators of intercellular communication (Ibrahim and Marbán, 2016), are released by major cardiac cells, including cardiomyocytes, fibroblasts and endothelial cells (Barile et al, 2017), to regulate cellular function (Poe and Knowlton, 2018). Direct use of paracrine factors is an attractive strategy that play a role in therapy via cytokine regulatory pathway, taking cell implantation or survival rate out of considered (Han C. S. et al, 2019). The development of injectable hydrogel nanocomposites for composite exosomes has raise researchers' attention since hydrogels are appropriate carrier materials.…”

Section: Cell Active Factormentioning

confidence: 99%

Injectable Hydrogel-Based Nanocomposites for Cardiovascular Diseases

Liao

Yang

Deng

et al. 2020

Front. Bioeng. Biotechnol.

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Cardiovascular diseases (CVDs), including a series of pathological disorders, severely affect millions of people all over the world. To address this issue, several potential therapies have been developed for treating CVDs, including injectable hydrogels as a minimally invasive method. However, the utilization of injectable hydrogel is a bit restricted recently owing to some limitations, such as transporting the therapeutic agent more accurately to the target site and prolonging their retention locally. This review focuses on the advances in injectable hydrogels for CVD, detailing the types of injectable hydrogels (natural or synthetic), especially that complexed with stem cells, cytokines, nano-chemical particles, exosomes, genetic material including DNA or RNA, etc. Moreover, we summarized the mainly prominent mechanism, based on which injectable hydrogel present excellent treating effect of cardiovascular repair. All in all, it is hopefully that injectable hydrogel-based nanocomposites would be a potential candidate through cardiac repair in CVDs treatment.

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Human umbilical cord mesenchymal stem cell derived exosomes encapsulated in functional peptide hydrogels promote cardiac repair

Abstract: Stem cell-derived exosomes have been recognized as a potential therapy for cardiovascular disease.

Cited by 191 publications

References 51 publications

Biomaterials Functionalized with MSC Secreted Extracellular Vesicles and Soluble Factors for Tissue Regeneration

Biomaterials Functionalized with MSC Secreted Extracellular Vesicles and Soluble Factors for Tissue Regeneration

Designer Self‐Assembling Peptide Hydrogels to Engineer 3D Cell Microenvironments for Cell Constructs Formation and Precise Oncology Remodeling in Ovarian Cancer

Injectable Hydrogel-Based Nanocomposites for Cardiovascular Diseases

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