Integrated Bioactive Scaffold with Polydeoxyribonucleotide and Stem-Cell-Derived Extracellular Vesicles for Kidney Regeneration

Ko, Kyoung-Won; Park, So‐Yeon; Lee, Eun Hye; Yoo, Yong-In; Kim, Da-Seul; Kim, Jun Yong; Kwon, Tae Gyun; Han, Dong Keun

doi:10.1021/acsnano.1c01098

Cited by 56 publications

(56 citation statements)

References 50 publications

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“…Many studies have raised the possibility of being used as an alternative to cell-based therapy because exosomes represented the characteristics of the cell of origin [19,20]. In particular, MSCs-derived exosomes have emerged as promising therapeutic agents for regenerative medicine, including angiogenesis and wound repair [21,22], kidney regeneration [23], cardiac repair [24], neurodegeneration treatment [25], and osteochondral regeneration [26]. The therapeutic effect of exosome is influenced by the differences in the molecular components (e.g.…”

Section: Introductionmentioning

confidence: 99%

Comparative Analysis of MSC-Derived Exosomes Depending on Cell Culture Media for Regenerative Bioactivity

Kim

Rhim

Seo

et al. 2021

Tissue Eng Regen Med

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BACKGROUND: In order to produce and isolate the exosome derived from the cell of interests, a serum free environment (starvation) has been essential for excluding the unknown effect from serum-derived exosomes. Recently, serum-free culture media have been developed as a substitute for serum supplemented media so that MSC proliferates with maintaining the original characteristics of the cells in a serum free condition. Due to the different properties of the exosomes representing the states and characteristics of the origin cells, a study is needed to compare the properties of the cell-derived exosomes according to the cell culture media. METHODS: To compare the cell culture condition on exosomes, human umbilical cord mesenchymal stem cells (UCMSCs) were cultured with two different media, serum containing media, 10% FBS supplemented DMEM (NM) and serum-free chemically defined media, CellCor TM CD MSC (CDM). To remove FBS-derived exosomes from UCMSC cultured with NM, the medium was replaced with FBS-free DMEM for starvation during exosome isolation. The production yield and expression levels of angiogenic and pro-inflammatory factors were compared. And, the subpopulations of exosome were classified depending on the surface properties and loaded cytokines. Finally, the wound healing and angiogenic effects have been evaluated using in vitro assays. RESULTS: The UCMSC-derived exosomes under two different cell culture media could be classified into subpopulations according to the surface composition and loaded cytokines. Especially, exosome derived from UCMSC cultured with CDM showed higher expression levels of cytokines related to regenerative bioactivities which resulted in enhanced wound healing and angiogenesis. CONCLUSION: CDM has the advantages to maintain cell proliferation even during the period of exosome isolations and eliminate unknown side effects caused by serumderived exosomes. Additionally, exosomes derived from UCMSC cultured with CDM show better wound healing and angiogenic effects due to a lot of regeneration-related cytokines and less pro-inflammatory cytokines compared to with NM.

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Section: Introductionmentioning

confidence: 99%

Comparative Analysis of MSC-Derived Exosomes Depending on Cell Culture Media for Regenerative Bioactivity

Kim

Rhim

Seo

et al. 2021

Tissue Eng Regen Med

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“…Nevertheless, scaffolds from synthetic polymers lack natural biomolecular signals which cells benefit from to modulate their functions. These signals can be provided by either adding bioactive agents like proteins into the polymer through blending or coating to recapitulate natural tissue [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Electrospinning Fabrication Methods to Incorporate Laminin in Polycaprolactone for Kidney Tissue Engineering

Baskapan

Callanan

2021

Tissue Eng Regen Med

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BACKGROUND: Today’s treatment options for renal diseases fall behind the need, as the number of patients has increased considerably over the last few decades. Tissue engineering (TE) is one avenue which may provide a new approach for renal disease treatment. This involves creating a niche where seeded cells can function in an intended way. One approach to TE is combining natural extracellular matrix proteins with synthetic polymers, which has been shown to have many positives, yet a little is understood in kidney. Herein, we investigate the incorporation of laminin into polycaprolactone electrospun scaffolds. METHOD: The scaffolds were enriched with laminin via either direct blending with polymer solution or in a form of emulsion with a surfactant. Renal epithelial cells (RC-124) were cultured on scaffolds up to 21 days. RESULTS: Mechanical characterization demonstrated that the addition of the protein changed Young’s modulus of polymeric fibres. Cell viability and DNA quantification tests revealed the capability of the scaffolds to maintain cell survival up to 3 weeks in culture. Gene expression analysis indicated healthy cells via three key markers. CONCLUSION: Our results show the importance of hybrid scaffolds for kidney tissue engineering.

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“…However, it has been reported that its degradation byproducts, lactic acid and glycolic acid cause an acidic microenvironment at implanting site [ 4 , 5 ]. In previous studies, magnesium hydroxide (MH) performed outstanding pH neutralization ability for diverse tissue regeneration [ 6 , 7 , 8 , 9 , 10 , 11 ], in particular, bone repair [ 12 , 13 , 14 ]. However, MH as a hydrophilic inorganic molecule is difficult to disperse evenly in the hydrophobic polymer-based scaffold.…”

Section: Introductionmentioning

confidence: 99%

Promotion of Bone Regeneration Using Bioinspired PLGA/MH/ECM Scaffold Combined with Bioactive PDRN

et al. 2021

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Current approaches of biomaterials for the repair of critical-sized bone defects still require immense effort to overcome numerous obstacles. The biodegradable polymer-based scaffolds have been required to expand further function for bone tissue engineering. Poly(lactic-co-glycolic) acid (PLGA) is one of the most common biopolymers owing to its biodegradability for tissue regenerations. However, there are major clinical challenges that the byproducts of the PLGA cause an acidic environment of implanting site. The critical processes in bone repair are osteogenesis, angiogenesis, and inhibition of excessive osteoclastogenesis. In this study, the porous PLGA (P) scaffold was combined with magnesium hydroxide (MH, M) and bone-extracellular matrix (bECM, E) to improve anti-inflammatory ability and osteoconductivity. Additionally, the bioactive polydeoxyribonucleotide (PDRN, P) was additionally incorporated in the existing PME scaffold. The prepared PMEP scaffold has pro-osteogenic and pro-angiogenic effects and inhibition of osteoclast due to the PDRN, which interacts with the adenosine A2A receptor agonist that up-regulates expression of vascular endothelial growth factor (VEGF) and down-regulates inflammatory cytokines. The PMEP scaffold has superior biological properties for human bone-marrow mesenchymal stem cells (hBMSCs) adhesion, proliferation, and osteogenic differentiation in vitro. Moreover, the gene expressions related to osteogenesis and angiogenesis of hBMSCs increased and the inflammatory factors decreased on the PMEP scaffold. In conclusion, it provides a promising strategy and clinical potential candidate for bone tissue regeneration and repairing bone defects.

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Integrated Bioactive Scaffold with Polydeoxyribonucleotide and Stem-Cell-Derived Extracellular Vesicles for Kidney Regeneration

Cited by 56 publications

References 50 publications

Comparative Analysis of MSC-Derived Exosomes Depending on Cell Culture Media for Regenerative Bioactivity

Comparative Analysis of MSC-Derived Exosomes Depending on Cell Culture Media for Regenerative Bioactivity

Electrospinning Fabrication Methods to Incorporate Laminin in Polycaprolactone for Kidney Tissue Engineering

Promotion of Bone Regeneration Using Bioinspired PLGA/MH/ECM Scaffold Combined with Bioactive PDRN

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