CHITOSAN-BASED SCAFFOLD COUNTERACTS HYPERTROPHYC AND FIBROTIC MARKERS IN CHONDROGENIC DIFFERENTIATED MESENCHYMAL STROMAL CELLS

Cristina Manferdini, Elena Gabusi, Luciana Sartore, Kamol Dey, Silvia Agnelli, Camillo Almici, Andrea Bianchetti, Nicoletta Zini, Domenico Russo, Federica Re, Erminia Mariani, Gina Lisignoli

Research output: Contribution to journalArticle

Abstract

Cartilage tissue engineering remains problematic since no systems are able to induce signals that contribute to native cartilage structure formation. Therefore, we tested the potentiality of gelatin-polyethylene glycol scaffolds containing three different concentrations of chitosan (CH) (0%, 8% and 16%) on chondrogenic differentiation of human platelet lysate (HPL)-expanded human bone marrow mesenchymal stromal cells (hBM-MSCs). Typical chondrogenic (SOX9, collagen type 2 and aggrecan), hypertrophic (collagen type 10) and fibrotic (collagen type 1) markers were evaluated at gene and protein level at day 1, 28 and 48. We demonstrated that 16% CH scaffold had the highest percentage of relaxation with the fastest relaxation rate. In particular, 16% CH scaffold, combined with chondrogenic factor TGFβ3, was more efficient in inducing hBM-MSCs chondrogenic differentiation compared to 0% or 8% scaffolds. Collagen type 2, SOX9 and aggrecan showed the same expression in all scaffolds, while collagen type 10 and collagen type 1 markers were efficiently down-modulated only in 16% CH. We demonstrated that using HPL chronically during hBM-MSCs chondrogenic differentiation, the chondrogenic, hypertrophic and fibrotic markers were significantly decreased. Our data demonstrate that only a high concentration of CH, combined with TGFβ3, creates an environment capable of guiding in vitro hBM-MSCs towards a phenotypically stable chondrogenesis.

Original languageEnglish
JournalJournal of Tissue Engineering and Regenerative Medicine
DOIs
Publication statusE-pub ahead of print - Jul 26 2019

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Collagen Type X
Chitosan
Mesenchymal Stromal Cells
Collagen
Scaffolds
Bone
Aggrecans
Collagen Type II
Cartilage
Collagen Type I
Platelets
Scaffolds (biology)
Cell Differentiation
Gelatin
Blood Platelets
Tissue engineering
Chondrogenesis
Polyethylene glycols
Tissue Engineering
Genes

Keywords

  • chitosan scaffold
  • chondrogenic differentiation
  • fibrotic markers
  • human platelet lysate
  • hypertrophic markers
  • mesenchymal stromal cells
  • stress relaxation

Cite this

CHITOSAN-BASED SCAFFOLD COUNTERACTS HYPERTROPHYC AND FIBROTIC MARKERS IN CHONDROGENIC DIFFERENTIATED MESENCHYMAL STROMAL CELLS. / Manferdini, Cristina; Gabusi, Elena; Sartore, Luciana; Dey, Kamol; Agnelli, Silvia; Almici, Camillo; Bianchetti, Andrea; Zini, Nicoletta; Russo, Domenico; Re, Federica; Mariani, Erminia; Lisignoli, Gina.

In: Journal of Tissue Engineering and Regenerative Medicine, 26.07.2019.

Research output: Contribution to journalArticle

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abstract = "Cartilage tissue engineering remains problematic since no systems are able to induce signals that contribute to native cartilage structure formation. Therefore, we tested the potentiality of gelatin-polyethylene glycol scaffolds containing three different concentrations of chitosan (CH) (0{\%}, 8{\%} and 16{\%}) on chondrogenic differentiation of human platelet lysate (HPL)-expanded human bone marrow mesenchymal stromal cells (hBM-MSCs). Typical chondrogenic (SOX9, collagen type 2 and aggrecan), hypertrophic (collagen type 10) and fibrotic (collagen type 1) markers were evaluated at gene and protein level at day 1, 28 and 48. We demonstrated that 16{\%} CH scaffold had the highest percentage of relaxation with the fastest relaxation rate. In particular, 16{\%} CH scaffold, combined with chondrogenic factor TGFβ3, was more efficient in inducing hBM-MSCs chondrogenic differentiation compared to 0{\%} or 8{\%} scaffolds. Collagen type 2, SOX9 and aggrecan showed the same expression in all scaffolds, while collagen type 10 and collagen type 1 markers were efficiently down-modulated only in 16{\%} CH. We demonstrated that using HPL chronically during hBM-MSCs chondrogenic differentiation, the chondrogenic, hypertrophic and fibrotic markers were significantly decreased. Our data demonstrate that only a high concentration of CH, combined with TGFβ3, creates an environment capable of guiding in vitro hBM-MSCs towards a phenotypically stable chondrogenesis.",
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AU - Manferdini, Cristina

AU - Gabusi, Elena

AU - Sartore, Luciana

AU - Dey, Kamol

AU - Agnelli, Silvia

AU - Almici, Camillo

AU - Bianchetti, Andrea

AU - Zini, Nicoletta

AU - Russo, Domenico

AU - Re, Federica

AU - Mariani, Erminia

AU - Lisignoli, Gina

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PY - 2019/7/26

Y1 - 2019/7/26

N2 - Cartilage tissue engineering remains problematic since no systems are able to induce signals that contribute to native cartilage structure formation. Therefore, we tested the potentiality of gelatin-polyethylene glycol scaffolds containing three different concentrations of chitosan (CH) (0%, 8% and 16%) on chondrogenic differentiation of human platelet lysate (HPL)-expanded human bone marrow mesenchymal stromal cells (hBM-MSCs). Typical chondrogenic (SOX9, collagen type 2 and aggrecan), hypertrophic (collagen type 10) and fibrotic (collagen type 1) markers were evaluated at gene and protein level at day 1, 28 and 48. We demonstrated that 16% CH scaffold had the highest percentage of relaxation with the fastest relaxation rate. In particular, 16% CH scaffold, combined with chondrogenic factor TGFβ3, was more efficient in inducing hBM-MSCs chondrogenic differentiation compared to 0% or 8% scaffolds. Collagen type 2, SOX9 and aggrecan showed the same expression in all scaffolds, while collagen type 10 and collagen type 1 markers were efficiently down-modulated only in 16% CH. We demonstrated that using HPL chronically during hBM-MSCs chondrogenic differentiation, the chondrogenic, hypertrophic and fibrotic markers were significantly decreased. Our data demonstrate that only a high concentration of CH, combined with TGFβ3, creates an environment capable of guiding in vitro hBM-MSCs towards a phenotypically stable chondrogenesis.

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KW - fibrotic markers

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