Self-assembled GFFYK peptide hydrogel enhances the therapeutic efficacy of mesenchymal stem cells in a mouse hindlimb ischemia model

Huang, Anan; Liu, Danni; Qi, Xin; Yue, Zhiwei; Cao, Hongmei; Zhang, Kaiyue; Lei, Xudan; Wang, Youzhi; Kong, Deling; Gao, Jie; Li, Zongjin; Liu, Na; Wang, Yuebing

doi:10.1016/j.actbio.2018.12.015

Cited by 39 publications

(41 citation statements)

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“…A significant portion of tissue engineering research focuses on the ability to derive native biological structures as biomaterials for regenerative purposes [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. Biomimetic structures, in particular, strive to recreate naturally regenerative microenvironments to promote desired cell behavior and mitigate inflammatory responses [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Micropatterning Decellularized ECM as a Bioactive Surface to Guide Cell Alignment, Proliferation, and Migration

et al. 2020

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Bioactive surfaces and materials have displayed great potential in a variety of tissue engineering applications but often struggle to completely emulate complex bodily systems. The extracellular matrix (ECM) is a crucial, bioactive component in all tissues and has recently been identified as a potential solution to be utilized in combination with biomaterials. In tissue engineering, the ECM can be utilized in a variety of applications by employing the biochemical and biomechanical cues that are crucial to regenerative processes. However, viable solutions for maintaining the dimensionality, spatial orientation, and protein composition of a naturally cell-secreted ECM remain challenging in tissue engineering. Therefore, this work used soft lithography to create micropatterned polydimethylsiloxane (PDMS) substrates of a three-dimensional nature to control cell adhesion and alignment. Cells aligned on the micropatterned PDMS, secreted and assembled an ECM, and were decellularized to produce an aligned matrix biomaterial. The cells seeded onto the decellularized, patterned ECM showed a high degree of alignment and migration along the patterns compared to controls. This work begins to lay the groundwork for elucidating the immense potential of a natural, cell-secreted ECM for directing cell function and offers further guidance for the incorporation of natural, bioactive components for emerging tissue engineering technologies.

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Section: Introductionmentioning

confidence: 99%

Micropatterning Decellularized ECM as a Bioactive Surface to Guide Cell Alignment, Proliferation, and Migration

et al. 2020

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“…MSCs, located within the stroma of the bone marrow, placenta, umbilical cord, and adipose tissue, are adult stem cells with self-renewal and multi-directional differentiation potentials [34,35]. It has been proposed that the therapeutic effects of MSCs after transplantation are mainly caused by a paracrine manner and initiate repair by immunomodulation, proliferation and anti-apoptosis, and stimulation of neovascularization [36,37].…”

Section: Discussionmentioning

confidence: 99%

Enhanced therapeutic effects of MSC-derived extracellular vesicles with an injectable collagen matrix for experimental acute kidney injury treatment

et al. 2020

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Background: Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have been shown to have therapeutic potential for ischemic diseases and are considered an alternative to cell therapy. However, the low retention and poor stability of EVs post-transplantation in vivo remain obstacle prior to the clinical application of EVs. Methods: This study was designed to investigate whether collagen matrix could increase the retention and stability of EVs and further improve the therapeutic effects in murine acute kidney injury (AKI) model. EVs were isolated from human placental MSCs (hP-MSC-EVs) and encapsulated in a collagen matrix. Then, we investigated whether collagen matrix can prolong the retention of EVs in vivo, further enhancing the therapeutic efficiency of EVs in AKI. Results: Our results indicated that collagen matrix could effectively encapsulate EVs, significantly increase the stability of EVs, and promote the sustained release of EVs. Collagen matrix has improved the retention of EVs in the AKI model, which was proved by Gaussia luciferase (Gluc) imaging. The application of collagen matrix remarkably facilitated the proliferation of renal tubular epithelial cells in AKI compared with EVs alone. Moreover, collagen matrix could further augment the therapeutic effects of hP-MSC-EVs as revealed by angiogenesis, fibrosis and apoptosis, and functional analysis. Finally, we found that EVs play a therapeutic role by inhibiting endoplasmic reticulum (ER) stress. Conclusions: Collagen matrix markedly enhanced the retention of EVs and further augmented the therapeutic effects of EVs for AKI. This strategy for improving the efficacy of EVs therapy provides a new direction for cell-free therapy.

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“…[ 77a,94 ] Consequently, MSCs have been encapsulated in different biomaterials for CLTI management. [ 85,87,88,90–93,95,96 ] A construct of autologous bone marrow stem cells (BMSCs), seeded in a collagen solution forming a porous scaffold, was able to induce the formation of mature vessels and oxygen saturation in a preclinical model. Collagen acted not only as a cellular delivery system but also as an angiogenic inducer by itself, showing a better effect than BMSCs alone.…”

Section: Biomaterials Application For Cltimentioning

confidence: 99%

“…The synthetic peptide hydrogel performed as a favorable niche to promote cell survival, as well as promoting the secretion of pro‐angiogenic factor. [ 88 ] The new system was able to induce revascularization, angiogenesis, and cause a decrease in inflammatory cell infiltration and collagen deposition. [ 88 ] Furthermore, a hybrid construct made of C‐domain of insulin‐like growth factor‐1 (IGF‐1C)‐chitosan was used to deliver MSCs in a mouse model of CLTI, showing improved revascularization due to the activation of the receptors for VEGFRs pathway.…”

Section: Biomaterials Application For Cltimentioning

confidence: 99%

“…[ 88 ] The new system was able to induce revascularization, angiogenesis, and cause a decrease in inflammatory cell infiltration and collagen deposition. [ 88 ] Furthermore, a hybrid construct made of C‐domain of insulin‐like growth factor‐1 (IGF‐1C)‐chitosan was used to deliver MSCs in a mouse model of CLTI, showing improved revascularization due to the activation of the receptors for VEGFRs pathway. [ 87 ] Another example of an ECM‐based system is a novel fibrinogen‐rich platelet lysate recently developed to deliver MSCs.…”

Section: Biomaterials Application For Cltimentioning

confidence: 99%

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Therapeutic Biomaterial Approaches to Alleviate Chronic Limb Threatening Ischemia

2021

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Chronic limb threatening ischemia (CLTI) is a severe condition defined by the blockage of arteries in the lower extremities that leads to the degeneration of blood vessels and is characterized by the formation of non‐healing ulcers and necrosis. The gold standard therapies such as bypass and endovascular surgery aim at the removal of the blockage. These therapies are not suitable for the so‐called “no option patients” which present multiple artery occlusions with a likelihood of significant limb amputation. Therefore, CLTI represents a significant clinical challenge, and the efforts of developing new treatments have been focused on stimulating angiogenesis in the ischemic muscle. The delivery of pro‐angiogenic nucleic acid, protein, and stem cell‐based interventions have limited efficacy due to their short survival. Engineered biomaterials have emerged as a promising method to improve the effectiveness of these latter strategies. Several synthetic and natural biomaterials are tested in different formulations aiming to incorporate nucleic acid, proteins, stem cells, macrophages, or endothelial cells in supportive matrices. In this review, an overview of the biomaterials used alone and in combination with growth factors, nucleic acid, and cells in preclinical models is provided and their potential to induce revascularization and regeneration for CLTI applications is discussed.

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Self-assembled GFFYK peptide hydrogel enhances the therapeutic efficacy of mesenchymal stem cells in a mouse hindlimb ischemia model

Cited by 39 publications

References 39 publications

Micropatterning Decellularized ECM as a Bioactive Surface to Guide Cell Alignment, Proliferation, and Migration

Micropatterning Decellularized ECM as a Bioactive Surface to Guide Cell Alignment, Proliferation, and Migration

Enhanced therapeutic effects of MSC-derived extracellular vesicles with an injectable collagen matrix for experimental acute kidney injury treatment

Therapeutic Biomaterial Approaches to Alleviate Chronic Limb Threatening Ischemia

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