Parathyroid hormone (1-34) promotes the effects of 3D printed scaffold-seeded bone marrow mesenchymal stem cells on meniscus regeneration

Wen Zhao,Tong Zou,Xia Zhang,Chenmei Ruan,Dengke Gao,Hao Cui,Yihua Zhang,Yangou Lv

doi:10.1186/s13287-020-01845-x

Wen Zhao, Tong Zou + Show 6 more

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https://doi.org/10.1186/s13287-020-01845-x

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Abstract

BackgroundCell-based tissue engineering represents a promising management for meniscus repair and regeneration. The present study aimed to investigate whether the injection of parathyroid hormone (PTH) (1-34) could promote the regeneration and chondroprotection of 3D printed scaffold seeded with bone marrow mesenchymal stem cells (BMSCs) in a canine total meniscal meniscectomy model.Methods3D printed poly(e-caprolactone) scaffold seeded with BMSCs was cultured in vitro, and the effects of in vitro culture time on cell growth and matrix synthesis of the BMSCs–scaffold construct were evaluated by microscopic observation and cartilage matrix content detection at 7, 14, 21, and 28 days. After that, the tissue-engineered meniscus based on BMSCs–scaffold cultured for the appropriate culture time was selected for in vivo implantation. Sixteen dogs were randomly divided into four groups: PTH + BMSCs–scaffold, BMSCs–scaffold, total meniscectomy, and sham operation. The regeneration of the implanted tissue and the degeneration of articular cartilage were assessed by gross, histological, and immunohistochemical analysis at 12 weeks postoperatively.ResultsIn vitro study showed that the glycosaminoglycan (GAG)/DNA ratio and the expression of collagen type II (Col2) were significantly higher on day 21 as compared to the other time points. In vivo study showed that, compared with the BMSCs–scaffold group, the PTH + BMSCs–scaffold group showed better regeneration of the implanted tissue and greater similarity to native meniscus concerning gross appearance, cell composition, and cartilage extracellular matrix deposition. This group also showed less expression of terminal differentiation markers of BMSC chondrogenesis as well as lower cartilage degeneration with less damage on the knee cartilage surface, higher expression of Col2, and lower expression of degeneration markers.ConclusionsOur results demonstrated that PTH (1-34) promotes the regenerative and chondroprotective effects of the BMSCs–3D printed meniscal scaffold in a canine model, and thus, their combination could be a promising strategy for meniscus tissue engineering.

Highlights

Cell-based tissue engineering represents a promising management for meniscus repair and regeneration
The main steps involved in meniscus tissue engineering are preparing a scaffold and seeding cells and regulating the cell–scaffold construct through cytokines, mechanical stimulation, and other methods to synthesize the extracellular matrix (ECM) in vitro, followed by its transplantation in vivo for meniscus regeneration and function [4]. 3D printing technology can fabricate scaffolds with complete control of size, shape, and porosity; it has been used in many previous studies to prepare tissue-engineered meniscus scaffolds [5,6,7,8]
The purpose of this study was to optimize the 3D printed PCL meniscus scaffolds seeded with bone marrow mesenchymal stem cells (BMSCs) and cultured in vitro and to investigate the effect of parathyroid hormone (PTH) (134) on the repairing of the tissue-engineered meniscus in vivo after implantation in the total meniscectomy canine model

Summary

Introduction

Cell-based tissue engineering represents a promising management for meniscus repair and regeneration. The main steps involved in meniscus tissue engineering are preparing a scaffold and seeding cells and regulating the cell–scaffold construct through cytokines, mechanical stimulation, and other methods to synthesize the extracellular matrix (ECM) in vitro, followed by its transplantation in vivo for meniscus regeneration and function [4]. Bone marrow mesenchymal stem cells (BMSCs) are easy to isolate and proliferate, have low immunogenicity, and have the potential to differentiate into cartilage; they have become ideal seed cell for meniscus tissue engineering [9, 10]. The influence of the in vitro culture time on the growth and differentiation of seed cells in meniscus tissue engineering has not been determined. Tissueengineered meniscus transplantation can promote the recovery of knee joint function, it causes different degrees of damage to knee cartilage and subchondral bone [14, 15]

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