scholarly journals Hyaline cartilage differentiation of fibroblasts in regeneration and regenerative medicine

Development ◽  
2022 ◽  
Author(s):  
Ling Yu ◽  
Yu-Lieh Lin ◽  
Mingquan Yan ◽  
Tao Li ◽  
Emily Y. Wu ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Regenerative Medicine ◽  
Hyaline Cartilage ◽  
Fibroblast Cell ◽  
Similar Response ◽  
Articular Chondrocyte ◽  
Joint Injury ◽  
A Cell ◽  
Culture Strategy

Amputation injuries in mammals are typically non-regenerative, however joint regeneration is stimulated by BMP9 treatment (Yu et al., 2019) indicating the presence of latent articular chondrocyte progenitor cells. BMP9 induces a battery of chondrogenic genes in vivo, and a similar response is observed in cultures of amputation wound cells. Extended cultures of BMP9 treated cells results in differentiation of hyaline cartilage and single cell RNAseq analysis identified wound fibroblasts as BMP9 responsive. This culture model was used to identify a BMP9 responsive adult fibroblast cell line and a culture strategy was developed to engineer hyaline cartilage for engraftment into an acutely damaged joint. Transplanted hyaline cartilage survived engraftment and maintained a hyaline cartilage phenotype but did not form mature articular cartilage. In addition, individual hypertrophic chondrocytes were identified in some samples indicating that the acute joint injury site can promote osteogenic progression of engrafted hyaline cartilage. The findings identify fibroblasts as a cell source for engineering articular cartilage and establishes a novel experimental strategy that bridges the gap between regeneration biology and regenerative medicine.

scholarly journals The Importance of Physioxia in Mesenchymal Stem Cell Chondrogenesis and the Mechanisms Controlling Its Response

2019 ◽  
Vol 20 (3) ◽  
pp. 484 ◽  
Author(s):  
Girish Pattappa ◽  
Brian Johnstone ◽  
Johannes Zellner ◽  
Denitsa Docheva ◽  
Peter Angele
Keyword(s):  
Articular Cartilage ◽  
Adult Population ◽  
Tissue Formation ◽  
Joint Movement ◽  
Articular Chondrocyte ◽  
Low Oxygen ◽  
Joint Injury ◽  
Chondrocyte Phenotype

Articular cartilage covers the surface of synovial joints and enables joint movement. However, it is susceptible to progressive degeneration with age that can be accelerated by either previous joint injury or meniscectomy. This degenerative disease is known as osteoarthritis (OA) and it greatly affects the adult population. Cell-based tissue engineering provides a possible solution for treating OA at its earliest stages, particularly focal cartilage lesions. A candidate cell type for treating these focal defects are Mesenchymal Stem Cells (MSCs). However, present methods for differentiating these cells towards the chondrogenic lineage lead to hypertrophic chondrocytes and bone formation in vivo. Environmental stimuli that can stabilise the articular chondrocyte phenotype without compromising tissue formation have been extensively investigated. One factor that has generated intensive investigation in MSC chondrogenesis is low oxygen tension or physioxia (2–5% oxygen). In vivo articular cartilage resides at oxygen tensions between 1–4%, and in vitro results suggest that these conditions are beneficial for MSC expansion and chondrogenesis, particularly in suppressing the cartilage hypertrophy. This review will summarise the current literature regarding the effects of physioxia on MSC chondrogenesis with an emphasis on the pathways that control tissue formation and cartilage hypertrophy.

Compartmentalization of the matrix formed by nucleus pulposus and annulus fibrosus cells in alginate gel

2002 ◽  
Vol 30 (6) ◽  
pp. 874-878 ◽  
Author(s):  
E. Thonar ◽  
H. An ◽  
K. Masuda
Keyword(s):  
Nucleus Pulposus ◽  
Annulus Fibrosus ◽  
Articular Chondrocyte ◽  
Alginate Gel ◽  
Age Related ◽  
The Matrix ◽  
Disc Cells ◽  
A Cell ◽  
Associated Matrix

Intervertebral disc cells cultured in alginate gel are capable of reforming in alginate, a matrix that consists of two compartments: a rim of metabolically active cell-associated matrix and a more abundant, but metabolically less active, further removed matrix. At any one age and in most species, the cell-associated matrix formed by a nucleus pulposus or annulus fibrosus cell cultured in this way is less abundant than that formed by an articular chondrocyte. In both the cell-associated matrix and further removed matrix, the ratio of aggrecan to collagen is significantly higher in the case of nucleus pulposus than of annulus fibrosus, a feature that also distinguishes the matrices of the nucleus pulposus and annulus fibrosus in vivo. Nucleus pulposus and annulus fibrosus cells from older donors show a decreased ability to reform a cell-associated matrix rich in aggrecan. There is, however, some evidence that gene therapy and/or exposure of the cells to defined stimulatory factors can help overcome some of these age-related limitations. This contention is supported by recent evidence that nucleus pulposus and annulus fibrosus cells from adult donors can be manipulated to form, using the recently developed alginate-recovered chondrocyte system, a resilient tissue that bears many of the characteristics of the tissue in which these cells reside in vivo.

Cartilage-specific deletion of mTOR upregulates autophagy and protects mice from osteoarthritis

2014 ◽  
Vol 74 (7) ◽  
pp. 1432-1440 ◽  
Author(s):  
Yue Zhang ◽  
Faezeh Vasheghani ◽  
Ying-hua Li ◽  
Meryem Blati ◽  
Kayla Simeone ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Protein Kinase ◽  
Mammalian Target Of Rapamycin ◽  
Adenosine Monophosphate ◽  
Cartilage Degradation ◽  
Chondrocyte Apoptosis ◽  
A Cell ◽  
Mtor Signalling

ObjectivesMammalian target of rapamycin (mTOR) (a serine/threonine protein kinase) is a major repressor of autophagy, a cell survival mechanism. The specific in vivo mechanism of mTOR signalling in OA pathophysiology is not fully characterised. We determined the expression of mTOR and known autophagy genes in human OA cartilage as well as mouse and dog models of experimental OA. We created cartilage-specific mTOR knockout (KO) mice to determine the specific role of mTOR in OA pathophysiology and autophagy signalling in vivo.MethodsInducible cartilage-specific mTOR KO mice were generated and subjected to mouse model of OA. Human OA chondrocytes were treated with rapamycin and transfected with Unc-51–like kinase 1 (ULK1) siRNA to determine mTOR signalling.ResultsmTOR is overexpressed in human OA cartilage as well as mouse and dog experimental OA. Upregulation of mTOR expression co-relates with increased chondrocyte apoptosis and reduced expression of key autophagy genes during OA. Subsequently, we show for the first time that cartilage-specific ablation of mTOR results in increased autophagy signalling and a significant protection from destabilisation of medial meniscus (DMM)-induced OA associated with a significant reduction in the articular cartilage degradation, apoptosis and synovial fibrosis. Furthermore, we show that regulation of ULK1/adenosine monophosphate-activated protein kinase (AMPK) signalling pathway by mTOR may in part be responsible for regulating autophagy signalling and the balance between catabolic and anabolic factors in the articular cartilage.ConclusionsThis study provides a direct evidence of the role of mTOR and its downstream modulation of autophagy in articular cartilage homeostasis.

In vivo multimodal imaging of inflammation in articular cartilage after joint injury

2021 ◽  
Vol 29 ◽  
pp. S346-S347
Author(s):  
A. Ruiz ◽  
A. Duarte ◽  
D. Bravo ◽  
E. Ramos ◽  
C. Zhang ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Multimodal Imaging ◽  
Joint Injury

scholarly journals Mesenchymal Stem Cells in Oriented PLGA/ACECM Composite Scaffolds Enhance Structure-Specific Regeneration of Hyaline Cartilage in a Rabbit Model

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Weimin Guo ◽  
Xifu Zheng ◽  
Weiguo Zhang ◽  
Mingxue Chen ◽  
Zhenyong Wang ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Hyaline Cartilage ◽  
Rabbit Model ◽  
Cartilage Regeneration ◽  
Cartilage Defects ◽  
Composite Scaffolds ◽  
Human Cartilage ◽  
Native Cartilage

Articular cartilage lacks a blood supply and nerves. Hence, articular cartilage regeneration remains a major challenge in orthopedics. Decellularized extracellular matrix- (ECM-) based strategies have recently received particular attention. The structure of native cartilage exhibits complex zonal heterogeneity. Specifically, the development of a tissue-engineered scaffold mimicking the aligned structure of native cartilage would be of great utility in terms of cartilage regeneration. Previously, we fabricated oriented PLGA/ACECM (natural, nanofibrous, articular cartilage ECM) composite scaffolds. In vitro, we found that the scaffolds not only guided seeded cells to proliferate in an aligned manner but also exhibited high biomechanical strength. To detect whether oriented cartilage regeneration was possible in vivo, we used mesenchymal stem cell (MSC)/scaffold constructs to repair cartilage defects. The results showed that cartilage defects could be completely regenerated. Histologically, these became filled with hyaline cartilage and subchondral bone. Moreover, the aligned structure of cartilage was regenerated and was similar to that of native tissue. In conclusion, the MSC/scaffold constructs enhanced the structure-specific regeneration of hyaline cartilage in a rabbit model and may be a promising treatment strategy for the repair of human cartilage defects.

Hyaline Characteristics of Mechanically Induced Cartilaginous Tissues

2007 ◽  
Author(s):  
Kristy T. S. Palomares ◽  
Thomas A. Einhorn ◽  
Louis C. Gerstenfeld ◽  
Elise F. Morgan
Keyword(s):  
Articular Cartilage ◽  
Mrna Expression ◽  
Mechanical Loading ◽  
Biochemical Composition ◽  
Hyaline Cartilage ◽  
Cartilage Explants ◽  
Tissue Structure ◽  
In Vivo Model ◽  
Extracellular Matrix Components

The mechanical properties of hyaline cartilage depend heavily on tissue structure and biochemical composition. Glycosaminoglycans (GAGs) and collagen fibrils are the key extracellular matrix components of hyaline cartilage that bestow compressive and tensile stiffness, respectively.[1–2] In articular cartilage, a decline in GAG content and collagen organization with injury or with diseases such as osteoarthritis is intimately linked with a decline in mechanical function.[3] In tissue-engineered cartilage and articular cartilage explants, mechanical loading in vitro results in increased aggrecan mRNA expression, GAG content, and increased stiffness.[4–6] These findings suggest that mechanical loading could be applied in vivo to promote cartilage repair via modulation of gene expression, tissue structure, and tissue composition. We have previously developed an in vivo model of skeletal repair in which application of a controlled bending motion to a healing osteotomy gap results in formation of cartilage within the gap.[6] Using this model, we sought to characterize the biochemical composition and collagen structure of the mechanically induced cartilaginous tissue. The objectives of this study were: 1) to quantify the total GAG content and aggrecan mRNA expression; and 2) to characterize the collagen fiber orientation.

Ultrastructure of melanocyte-keratinocyte interactions and pigment transfer in vitro

1978 ◽  
Vol 36 (2) ◽  
pp. 650-651
Author(s):  
Raul I. Garcia ◽  
Evelyn A. Flynn ◽  
George Szabo
Keyword(s):  
Direct Injection ◽  
Skin Pigmentation ◽  
Freeze Fracture ◽  
Pigment Granule ◽  
Time Lapse ◽  
Ultrastructural Level ◽  
Lanthanum Tracer ◽  
A Cell

Skin pigmentation in mammals involves the interaction of epidermal melanocytes and keratinocytes in the structural and functional unit known as the Epidermal Melanin Unit. Melanocytes(M) synthesize melanin within specialized membrane-bound organelles, the melanosome or pigment granule. These are subsequently transferred by way of M dendrites to keratinocytes(K) by a mechanism still to be clearly defined. Three different, though not necessarily mutually exclusive, mechanisms of melanosome transfer have been proposed: cytophagocytosis by K of M dendrite tips containing melanosomes, direct injection of melanosomes into the K cytoplasm through a cell-to-cell pore or communicating channel formed by localized fusion of M and K cell membranes, release of melanosomes into the extracellular space(ECS) by exocytosis followed by K uptake using conventional phagocytosis. Variability in methods of transfer has been noted both in vivo and in vitro and there is evidence in support of each transfer mechanism. We Have previously studied M-K interactions in vitro using time-lapse cinemicrography and in vivo at the ultrastructural level using lanthanum tracer and freeze-fracture.

Analysis of the Dynamics of the Electric Capacitance of a Cell Monolayer at the Late Stages of Caco-2 cell Differentiation

2019 ◽  
Vol 35 (6) ◽  
pp. 87-90
Author(s):  
S.V. Nikulin ◽  
V.A. Petrov ◽  
D.A. Sakharov
Keyword(s):  
Impedance Spectroscopy ◽  
Cell Monolayer ◽  
Microfluidic Chips ◽  
Russian Science ◽  
Electric Capacitance ◽  
A Cell ◽  
Static Conditions ◽  
Late Stages

The real-time monitoring of electric capacitance (impedance spectroscopy) allowed obtaining evidence that structures which look like intestinal villi can be formed during the cultivation under static conditions as well as during the cultivation in microfluidic chips. It was shown in this work via transcriptome analysis that the Hh signaling pathway is involved in the formation of villus-like structures in vitro, which was previously shown for their formation in vivo. impedance spectroscopy, intestine, villi, electric capacitance, Hh The study was funded by the Russian Science Foundation (Project 16-19-10597).

scholarly journals In vivo targeting of lentiviral vectors pseudotyped with the Tupaia paramyxovirus H glycoprotein bearing a cell-specific ligand

2021 ◽  
Author(s):  
Takele Argaw ◽  
Michael P. Marino ◽  
Andrew Timmons ◽  
Lindsey Eldridge ◽  
Kazuyo Takeda ◽  
...  
Keyword(s):  
Lentiviral Vectors ◽  
A Cell ◽  
Specific Ligand
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