Functionalized self-assembling peptide nanofiber hydrogels mimic stem cell niche to control human adipose stem cell behavior in vitro

Liu, Xi; Wang, Xiumei; Wang, Xiujuan; Ren, Hui; He, Jin; Lin, Qiao; Cui, Fuzhai

doi:10.1016/j.actbio.2013.01.027

Cited by 111 publications

(100 citation statements)

References 44 publications

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“…These limitations will be improved in subsequent studies. In addition, we plan to further examine the fate of stem cells with the use of an apoptosis probe [20] and to determine whether we can strengthen the actions of the stem cells by creating a better environment [21].…”

Section: Discussionmentioning

confidence: 99%

Dual-modular molecular imaging to trace transplanted bone mesenchymal stromal cells in an acute myocardial infarction model

et al. 2015

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Section: Discussionmentioning

confidence: 99%

Dual-modular molecular imaging to trace transplanted bone mesenchymal stromal cells in an acute myocardial infarction model

et al. 2015

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“…The peptide solutions should be neutralized before cell seeding or transplantation in vivo [20][21] , in which case a solid hydrogel has already formed.…”

Section: Introductionmentioning

confidence: 99%

Functional Self-Assembling Peptide Nanofiber Hydrogels Designed for Nerve Degeneration

Sun

et al. 2016

ACS Appl. Mater. Interfaces

189

160

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Self-assembling peptide (SAP) RADA16-I (Ac-(RADA)4-CONH2) has been suffering from a main drawback associated with low pH, which damages cells and host tissues upon direct exposure. In this study, we presented a strategy to prepare nanofiber hydrogels from two designer SAPs at neutral pH. RADA16-I was appended with functional motifs containing cell adhesion peptide RGD and neurite outgrowth peptide IKVAV. The two SAPs were specially designed to have opposite net charges at neutral pH, the combination of which created a nanofiber hydrogel (-IKVAV/-RGD) characterized by significantly higher G' than G″ in a viscoelasticity examination. Circular dichroism, Fourier transform infrared spectroscopy, and Raman measurements were performed to investigate the secondary structure of the designer SAPs, indicating that both the hydrophobic/hydrophilic properties and electrostatic interactions of the functional motifs play an important role in the self-assembling behavior of the designer SAPs. The neural progenitor cells (NPCs)/stem cells (NSCs) fully embedded in the 3D-IKVAV/-RGD nanofiber hydrogel survived, whereas those embedded within the RADA 16-I hydrogel hardly survived. Moreover, the -IKVAV/-RGD nanofiber hydrogel supported NPC/NSC neuron and astrocyte differentiation in a 3D environment without adding extra growth factors. Studies of three nerve injury models, including sciatic nerve defect, intracerebral hemorrhage, and spinal cord transection, indicated that the designer -IKVAV/-RGD nanofiber hydrogel provided a more permissive environment for nerve regeneration than the RADA 16-I hydrogel. Therefore, we reported a new mechanism that might be beneficial for the synthesis of SAPs for in vitro 3D cell culture and nerve regeneration.

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“…29 Various bioactive short peptide motifs that act as growth factors or ECM macromolecules have been incorporated into the C-terminus of RADA16 to promote cell migration, proliferation, and differentiation. [30][31][32] These functionalized self-assembling peptide nanofiber scaffolds have exhibited extensive potential in bone, vascular, and neural regeneration. [32][33][34][35] The bone morphogenetic protein-7 (BMP7) is an important member of the transforming growth factor-b superfamily.…”

Section: Introductionmentioning

confidence: 99%

Biological Evaluation of Human Degenerated Nucleus Pulposus Cells in Functionalized Self-Assembling Peptide Nanofiber Hydrogel Scaffold

Tao

Zhang

Wang

et al. 2014

Tissue Engineering Part A

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Nucleus pulposus (NP) tissue engineering has been proposed as a novel biological treatment for early-stage intervertebral disc degeneration. In this study, a novel functional self-assembling peptide PKP was first designed by linking the short functional motif of bone morphogenetic protein-7 (BMP7) to the C-terminal of RADA16-I, and another new functional self-assembling peptide was obtained by mixing RKP with RADA16-I. Then, the biocompatibilities and bioactivities of RKP and RAD-RKP for human degenerated nucleus pulposus cells (hNPCs) were studied in vitro. Atomic force microscopy and scanning electron microscopy (SEM) confirmed that both RKP and RAD-RKP could self-assemble into three-dimensional (3D) nanofiber hydrogel scaffolds in a culture medium at 37°C. After the hNPCs were cultured in 3D scaffolds, both RKP and RAD-RKP exhibited reliable attachment and extremely low cytotoxicities (<14%), which were verified by SEM and cytotoxity assays, respectively. Our results also showed that the functional-based scaffolds could increase the proliferation and migration of hNPCs after 7 days compared with culture plates and pure RADA16-I. Quantitative real-time polymerase chain reaction demonstrated that the expressions of collagen II α1, Sox-9, and aggrecan were upregulated, while collagen I α1 was downregulated by functional-based scaffolds after 28 days. Furthermore, we also confirmed that RAD-RKP exhibited a higher hNPC proliferation, migration, and expression of Sox-9 and aggrecan compared with pure RKP. Therefore, the results of this study indicated that the BMP7 short motif-designed functional self-assembling peptide nanofiber hydrogels could be used as excellent scaffolds in NP tissue engineering, and RAD-RKP might have further potential application in human mild degenerated NP tissue regeneration.

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Functionalized self-assembling peptide nanofiber hydrogels mimic stem cell niche to control human adipose stem cell behavior in vitro

Cited by 111 publications

References 44 publications

Dual-modular molecular imaging to trace transplanted bone mesenchymal stromal cells in an acute myocardial infarction model

Dual-modular molecular imaging to trace transplanted bone mesenchymal stromal cells in an acute myocardial infarction model

Functional Self-Assembling Peptide Nanofiber Hydrogels Designed for Nerve Degeneration

Biological Evaluation of Human Degenerated Nucleus Pulposus Cells in Functionalized Self-Assembling Peptide Nanofiber Hydrogel Scaffold

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