scholarly journals Investigation of a functionalized self-assembling nanopeptide hydrogel loaded with adipose-derived mesenchymal stem cells to promote vascular regeneration

2020 ◽  
Author(s):  
Zhanao Liu ◽  
Ailing Tian ◽  
Xin Yi ◽  
Lufeng Fan ◽  
Wenchong Shao ◽  
...  

Abstract Objectives: To investigate the transplantation of a functionalized self-assembling nanopeptide hydrogel loaded with adipose-derived mesenchymal stem cells (AD-MSCs) into a rabbit hindlimb ischemia model and to evaluate its effect in promoting vascular regeneration in ischemic tissues.Methods: Functionalized self-assembling nanopeptide hydrogels were synthesized, and the physical and chemical properties of the hydrogels were observed by electron microscopy. Primary AD-MSCs were isolated, cultured, immunophenotyped, induced to differentiate, and verified. The self-assembling nanopeptide hydrogel was combined with mesenchymal stem cells for the three-dimensional culture of AD-MSCs, and the growth characteristics were investigated. Animal models were injected with AD-MSC-loaded self-assembled peptide hydrogel, and the therapeutic effects on arterial ischemia were analyzed.Results: The pore size of the functionalized self-assembling nanopeptide hydrogel was suitable for cell growth. Stem cells had a tendency for migration, differentiation, and angiogenesis in three-dimensional culture. The experimental results of transplantation into the rabbit hindlimb ischemia model showed that the functionalized self-assembling nanopeptide hydrogel loaded with AD-MSCs had better efficacy than AD-MSC transplantation alone.Conclusion: Functionalized self-assembling nanopeptide hydrogels can be used as scaffold materials for three-dimensional culture of AD-MSCs. Functionalized self-assembling peptide hydrogels combined with AD-MSCs have better therapeutic effects than traditional stem cell therapies and can promote vascular regeneration.

2020 ◽  
Author(s):  
Zhanao Liu ◽  
Ailing Tian ◽  
Xin Yi ◽  
Lufeng Fan ◽  
Wenchong Shao ◽  
...  

Abstract Background: To investigate the transplantation of a functionalized self-assembling nanopeptide hydrogel loaded with adipose-derived mesenchymal stem cells (AD-MSCs) into a rabbit hindlimb ischemia model and to evaluate its effect in promoting vascular regeneration in ischemic tissues.Methods: Functionalized self-assembling nanopeptide hydrogels were synthesized, and the physical and chemical properties of the hydrogels were observed by electron microscopy. Primary AD-MSCs were isolated, cultured, immunophenotyped, induced to differentiate, and verified. The self-assembling nanopeptide hydrogel was combined with mesenchymal stem cells for the three-dimensional culture of AD-MSCs, and the growth characteristics were investigated. Animal models were injected with AD-MSC-loaded self-assembled peptide hydrogel, and the therapeutic effects on arterial ischemia were analyzed.Results: The pore size of the functionalized self-assembling nanopeptide hydrogel was suitable for cell growth. Stem cells had a tendency for migration, differentiation, and angiogenesis in three-dimensional culture. The experimental results of transplantation into the rabbit hindlimb ischemia model showed that the functionalized self-assembling nanopeptide hydrogel loaded with AD-MSCs had better efficacy than AD-MSC transplantation alone.Conclusion: Functionalized self-assembling nanopeptide hydrogels can be used as scaffold materials for three-dimensional culture of AD-MSCs. Functionalized self-assembling peptide hydrogels combined with AD-MSCs have better therapeutic effects than traditional stem cell therapies and can promote vascular regeneration.


2021 ◽  
Vol 10 (1) ◽  
pp. 547-554
Author(s):  
Jianmin Ling ◽  
Ailing Tian ◽  
Xin Yi ◽  
Nianfeng Sun

Abstract To research the paracrine role of adipose tissue-derived mesenchymal stem cells (ADMSCs) in promoting angiogenesis under the three-dimensional culture conditions consisting of a functionalized self-assembling peptide nanofiber hydrogel. ADMSCs were isolated, extracted, and then identified. Three kinds of peptides (RADAI-16, RGD, and KLT) were prepared, and a functionalized self-assembling peptide nanofiber hydrogel was produced by mixing RADAI-16, RGD, and KLT in a volume ratio 2:1:1. AFM was used to observe RADAI-16, RGD, KLT, and the functionalized self-assembling peptide nanofiber hydrogel. Then, ADMSCs were cultured under three-dimensional conditions consisting of the peptide nanofiber hydrogel, and AFM was used to observe cell migration. The ADMSCs in the common culture group (37°C, 5% CO2 cell culture box) and hypoxic culture group (37°C, 10% CO2, and 1% O2 hypoxic culture box) acted as controls. ADMSCs were three-dimensionally cultured in situ for 1 day, and then the concentrations of HGF and VEGF in the supernatant were determined by ELISA. Cells were extracted from the peptide nanofiber hydrogel, and HO-1 expression was detected by western blotting. ADMSCs have high expression levels of CD29, CD90, and CDl05 and low expression levels of CD34 and CD45. In addition, they can differentiate into adipocytes and osteocytes. The diameters of the fibers of RADAI-16, RGD, KLT, and the functionalized self-assembling peptide hydrogel are 17.34 ± 1.82, 15.50 ± 1.41, 13.77 ± 1.18, and 20.26 ± 1.25 nm, respectively. AFM indicated that cells in the functionalized self-assembling peptide nanofiber hydrogel migrated farther than those in RADAI-16. The concentrations of HGF under common, hypoxic, and three-dimensional culture conditions were 47.31 ± 6.75, 247.86 ± 17.59, and 297.25 ± 17.95 pg/mL, respectively, while the concentrations of VEGF were 218.30 ± 3.03, 267.13 ± 4.27, and 289.14 ± 3.11 pg/mL, respectively. Both HGF and VEGF were expressed more in the presence of the functionalized self-assembling peptide nanofiber hydrogel than in its absence (P < 0.05). Using western blotting, ADMSCs cultured under hypoxic and three-dimensional conditions were found to have high expression levels of HO-1. Culturing ADMSCs under three-dimensional conditions consisting of functionalized self-assembling peptide nanofiber hydrogels can promote their paracrine role in angiogenesis, such as HGF and VEGF, and hypoxia is one of the important elements.


PLoS ONE ◽  
2018 ◽  
Vol 13 (11) ◽  
pp. e0206811 ◽  
Author(s):  
Jing Li ◽  
Tong Chen ◽  
Xiahe Huang ◽  
Yunshan Zhao ◽  
Bin Wang ◽  
...  

2011 ◽  
Vol 469 (10) ◽  
pp. 2744-2753 ◽  
Author(s):  
Isaac E. Erickson ◽  
Steven C. van Veen ◽  
Swarnali Sengupta ◽  
Sydney R. Kestle ◽  
Robert L. Mauck

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Xiaozhi Zhao ◽  
Xuefeng Qiu ◽  
Yanting Zhang ◽  
Shiwei Zhang ◽  
Xiaoping Gu ◽  
...  

It has been shown that administration of adipose derived mesenchymal stem cells (AdMSCs) enhanced structural and functional recovery of renal ischemia-reperfusion (IR) injury. Low engraftment of stem cells, however, limits the therapeutic effects of AdMSCs. The present study was designed to enhance the therapeutic effects of AdMSCs by delivering AdMSCs in a three-dimensional (3D) aggregates form. Microwell was used to produce 3D AdMSCs aggregates. In vitro data indicated that AdMSCs in 3D aggregates were less susceptible to oxidative and hypoxia stress induced by 200 μM peroxide and hypoxia/reoxygenation, respectively, compared with those cultured in two-dimensional (2D) monolayer. Furthermore, AdMSCs in 3D aggregates secreted more proangiogenic factors than those cultured in 2D monolayer. 2D AdMSCs or 3D AdMSCs aggregates were injected into renal cortex immediately after induction of renal IR injury. In vivo data revealed that 3D aggregates enhanced the effects of AdMSCs in recovering function and structure after renal IR injury. Improved grafted AdMSCs were observed in kidney injected with 3D aggregates compared with AdMSCs cultured in 2D monolayer. Our results demonstrated that 3D AdMSCs aggregated produced by microwell enhanced the retention and therapeutic effects of AdMSCs for renal IR injury.


2020 ◽  
Author(s):  
Kyungmin Koh ◽  
Mira Park ◽  
Eun Soo Bae ◽  
Van-An Duong ◽  
Jong-Moon Park ◽  
...  

Abstract Background: Stem cell transplantation has been proposed as an alternative treatment for intractable optic nerve disorders characterized by irrecoverable loss of cells. Mesenchymal stem cells, with varying tissue regeneration and recovery capabilities, are being considered for potential cell therapies. To overcome the limitations of cell therapy, we isolated exosomes from human placenta–derived mesenchymal stem cells (hPMSCs), and investigated their therapeutic effects in R28 cells (retinal precursor cells) exposed to CoCl2. Method: After nine hours of exposure to CoCl2, the hypoxic damaged R28 cells were divided into non treatment group (CoCl2+R28 cells) and treatment group (CoCl2+R28 cells treated with exosome). Immunoblot analysis was performed for Pcna, Hif-1α, Vegf, Vimentin, Thy-1, Gap43, Ermn, Neuroflament, Wnt3a, β-catenin, phospo-GSK3β, Lef-1, UBA2, Skp1, βTrcp, and ubiquitin. The proteomes of each group were analyzed by liquid chromatography/tandem mass (LC-MS/MS) spectrometry. Differentially expressed proteins (DEPs) were detected by label-free quantification and the interactions of the proteins were examined through signal transduction pathway and gene ontology analysis. Result: We observed that Exosome could significantly recover proliferation damaged by CoCl2 treatment. In addition, treatment group presented the decreased expression of Hif-1α protein (P < 0.05) and increased expression of proliferation marker, Pcna, and nerve regeneration–related factors such as Vimentin, Thy-1 and Neuroflament (P < 0.05) compared with non-treatment group. In total, 200 DEPs were identified in non-treatment group and treatment group (fold change ≥ 2, p < 0.05). Catenin and ubiquitin systems (UBA2, UBE2E3, UBE2I) were found in both the DEP lists of downregulated proteins from non-treatment group and upregulated proteins from treatment group. The mRNA expressions of ubiquitin systems were significantly decreased under hypoxic condition. Moreover, UBA2 and Wnt/β-catenin protein were associated with rescue of the hypoxic damaged R28 cells. Using a siRNA system, we could find it out that hPMSC exosoms could not repair altered expressions of target proteins by CoCl2 in lacking UBA2 R28 cells. Conclusion: This study reported that hypoxic damaged expression of regeneration markers in R28 cells were significantly recovered by hPMSC exosomes. We could also demonstrate that UBA2 played a key role in activating the Wnt/β-catenin signaling pathway during protection of hypoxic damaged R28 cells, induced by hPMSC exosomes.


Pancreatology ◽  
2017 ◽  
Vol 17 (3) ◽  
pp. S40
Author(s):  
Orsolya Hegedűs ◽  
Dávid Juriga ◽  
Krisztina Nagy ◽  
Angéla Jedlovszky-Hajdú ◽  
Miklós Zrínyi ◽  
...  

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