Combination Of Chondrocytes Research Articles

A comparative study on various cell sources for constructing tissue-engineered meniscus.

Injury to the meniscus is a common occurrence in the knee joint and its management remains a significant challenge in the clinic. Appropriate cell source is essential to cell-based tissue regeneration and cell therapy. Herein, three commonly used cell sources, namely, bone marrow mesenchymal stem cell (BMSC), adipose-derived stem cell (ADSC), and articular chondrocyte, were comparatively evaluated to determine their potential for engineered meniscus tissue in the absence of growth factor stimulus. Cells were seeded on electrospun nanofiber yarn scaffolds that share similar aligned fibrous configurations with native meniscus tissue for constructing meniscus tissue in vitro. Our results show that cells proliferated robustly along nanofiber yarns to form organized cell-scaffold constructs, which recapitulate the typical circumferential fiber bundles of native meniscus. Chondrocytes exhibited different proliferative characteristics and formed engineered tissues with distinct biochemical and biomechanical properties compared to BMSC and ADSC. Chondrocytes maintained good chondrogenesis gene expression profiles and produced significantly increased chondrogenic matrix and form mature cartilage-like tissue as revealed by typical cartilage lacunae. In contrast, stem cells underwent predominately fibroblastic differentiation and generated greater collagen, which contributes to improved tensile strengths of cell-scaffold constructs in comparison to the chondrocyte. ADSC showed greater proliferative activity and increased collagen production than BMSC. These findings indicate that chondrocytes are superior to stem cells for constructing chondrogenic tissues while the latter is feasible to form fibroblastic tissue. Combination of chondrocytes and stem cells might be a possible solution to construct fibrocartilage tissue and meniscus repair and regeneration.

Solid multifunctional granular bioink for constructing chondroid basing on stem cell spheroids and chondrocytes

Stem cell spheroids are advanced building blocks to produce chondroid. However, the multi-step operations including spheroids preparation, collection and transfer, the following 3D printing and shaping limit their application in 3D printing. The present study fabricates an ‘ALL-IN-ONE’ bioink based on granular hydrogel to not only produce adipose derived stem cell (ASC) spheroids, but also realize the further combination of chondrocytes and the subsequent 3D printing. Microgels (6–10 μm) grafted with β-cyclodextrin (β-CD) (MGβ-CD) were assembled and crosslinked by in-situ polymerized poly (N-isopropylacrylamide) (PNIPAm) to form bulk granular hydrogel. The host-guest action between β-CD of microgels and PNIPAm endows the hydrogel with stable, shear-thinning and self-healing properties. After creating caves, ASCs aggregate spontaneously to form numerous spheroids with diameter of 100–200 μm inside the hydrogel. The thermosensitive porous granular hydrogel exhibits volume change under different temperature, realizing further adsorbing chondrocytes. Then, the granular hydrogel carrying ASC spheroids and chondrocytes is extruded by 3D printer at room temperature to form a tube, which can shrink at cell culture temperature to enhance the resolution. The subsequent ASC spheroids/chondrocytes co-culture forms cartilage-like tissue at 21 d in vitro, which further matures subcutaneously in vivo, indicating the application potential of the fully synthetic granular hydrogel ink toward organoid culture.

Combination of chondrocytes and chondrons improves extracellular matrix production to promote the repairs of defective knee cartilage in rabbits.

BackgroundChondrons are composed of chondrocytes and the surrounding pericellular matrix (PCM) and function to enhance chondrocyte-mediated cartilage tissue engineering. This study aimed at investigating the potential effect of combined chondrocytes with chondrons on the production of proteoglycan and collagen-II (Col-2) and the repair of defective knee cartilage in rabbits.MethodsChondrocytes and chondrons were isolated from the knee cartilage of rabbits, and cultured alone or co-cultured for varying periods in vitro. Their morphology was characterized by histology. The levels of aggrecan (AGG), Col-2 and glycosaminoglycan (GAG) expression were quantified by qRT-PCR, Alcian blue-based precipitation and ELISA. The effect of combined chondrocytes with chondrons in alginate spheres on the repair of defective knee cartilage was examined in rabbits.ResultsThe isolated chondrocytes and chondrons displayed unique morphology and began to proliferate on day 3 and 6 post culture, respectively, accompanied by completely degenerated PCM on day 6 post culture. Evidently, chondrocytes had stronger proliferation capacity than chondrons. Longitudinal analyses indicated that culture of chondrons, but not chondrocytes, increased AGG mRNA transcripts and GAG levels with time and Col-2 mRNA transcripts only on day 3 post culture. Compared with chondrocytes or chondrons alone, co-culture of chondrocytes and chondrons significantly up-regulated AGG and Col-2 expression and GAG production, particularly at a ratio of 1:1. Implantation with chondrocytes and chondrons at 1:1 significantly promoted the repair of defective knee cartilage in rabbits, accompanied by reduced the Wakiteni scores with time.ConclusionCombined chondrons with chondrocytes promoted the production of extracellular matrix and the repair of defective knee cartilage in rabbits.The translational potential of this articleThis study explores that the combination of chondrons and chondrocytes may be new therapeutic strategy for cartilage tissue engineering and repair of defective cartilage.

Chitosan-hyaluronic acid hydrogel for cartilage repair

The current study investigates the potential of chitosan-hyaluronic acid dialdehyde hydrogels for in vivo cartilage regeneration following two different approaches: Gel alone for cartilage regeneration or combination of chondrocytes and gel for cartilage repair. Critical size osteochondral defects were created in knee joints of Newzealand White rabbits. Allogenic rabbit chondrocytes were encapsulated in hydrogels and gel or gel+cells were implanted in defects aseptically. The regenerated cartilage was analyzed after 12 weeks of implantation. The morphological scoring indicates that repair tissue was formed in all the animals by 12 weeks irrespective of whether they were sham, received gel, or gel with cells as implant. However the repair tissue formed in sham appeared fibrous and opaque, where as those that received gel had texture similar to the surrounding native cartilage and animals with gel+cells showed varied response. Histology staining, score distribution and immunostaining for collagen Type II showed animals that received gel alone as the implant had a mixture of hyaline and fibro cartilage. The animals with cell encapsulated gels had more fibrous cells with weak staining for collagen type II. There was no significant enhancement in the quality of regenerated cartilage in presence of encapsulated chondrocytes.

One-stage focal cartilage defect treatment with bone marrow mononuclear cells and chondrocytes leads to better macroscopic cartilage regeneration compared to microfracture in goats

The combination of chondrocytes and mononuclear fraction (MNF) cells might solve the expansion induced dedifferentiation problem of reimplanted cells in autologous chondrocytes implantation as sufficient cells would be available for direct, one-stage, implantation. Earlier invitro work already showed a positive stimulation of cartilage specific matrix production when chondrocytes and MNF cells were combined. Therefore, this study aimed to evaluate cartilage regeneration using a one-stage procedure combining MNF cells and primary chondrocytes for the treatment of focal cartilage lesions in goats compared to microfracture treatment. Freshly created focal cartilage defects were treated with either a combination of chondrocytes and MNF cells embedded in fibrin glue or microfracture treatment. After 6 months follow-up local regeneration as well as the general joint cartilage health were evaluated using validated scores and biochemical assays. Macroscopic (P=0.015) scores for the cartilage surface at the treated defect were, after 6 months, significantly higher for the chondrocyteMNF treatment compared to microfracture-treated defects, but microscopic scores were not (P=0.067). The articulating cartilage showed more (P=0.005) degeneration following microfracture treatment compared to chondrocyteMNF treatment. Biochemical glycosaminoglycans (GAG) evaluation did not reveal differences between the treatments. Both treatments had resulted in a slight to moderate cartilage degeneration at other locations in the joint. In conclusion, treatment of focal articular cartilage lesions in goats using a combination of MNF cells from bone marrow and unexpanded chondrocytes leads to better macroscopic regeneration compared to microfracture, however needs further fine-tuning to decrease the negative influence on other joint compartments.