scholarly journals Click chemistry-based pre-targeting cell delivery for cartilage regeneration

2021 ◽  
Vol 8 (3) ◽  
Author(s):  
Cynthia M Co ◽  
Samira Izuagbe ◽  
Jun Zhou ◽  
Ning Zhou ◽  
Xiankai Sun ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Click Chemistry ◽  
Ex Vivo ◽  
Cartilage Regeneration ◽  
Cartilage Injury ◽  
Cell Delivery ◽  
Polymer Carrier ◽  
Human Cartilage ◽  
Joint Injury ◽  
Cell Based Therapy

Abstract A fraction of the OA patient population is affected by post-traumatic osteoarthritis (PTOA) following acute joint injuries. Stopping or reversing the progression of PTOA following joint injury could improve long-term functional outcomes, reduced disability, and medical costs. To more effectively treat articular cartilage injury, we have developed a novel cell-based therapy that involves the pre-targeting of apoptotic chondrocytes and the delivery of healthy, metabolically active chondrocytes using click chemistry. Specifically, a pre-targeting agent was prepared via conjugating apoptotic binding peptide (ApoPep-1) and trans-cyclooctene (TCO) onto polyethylene glycol (PEG) polymer carrier. The pre-targeting agent would be introduced to injured areas of articular cartilage, leading to the accumulation of TCO groups on the injured areas from actively binding to apoptotic chondrocytes. Subsequently, methyltetrazine (Tz)-bearing chondrocytes would be immobilized on the surface of TCO-coated injured cartilage via Tz-TCO click chemistry reaction. Using an ex vivo human cartilage explant PTOA model, the effectiveness of this new approach was evaluated. Our studies show that this novel approach (Tz-TCO click chemistry) significantly enhanced the immobilization of healthy and metabolically active chondrocytes to the areas of apoptotic chondrocytes. Histological analyses demonstrated that this treatment regimen would significantly reduce the area of cartilage degeneration and enhance ECM regeneration. The results support that Tz-TCO click chemistry-mediated cell delivery approach has great potential in clinical applications for targeting and treatment of cartilage injury.

Influence of Permeability on the Compressive Property of Articular Cartilage: A Scaffold-Free, Stem Cell-Based Therapy for Cartilage Repair

2011 ◽  
Author(s):  
Tomoya Susa ◽  
Ryosuke Nansai ◽  
Norimasa Nakamura ◽  
Hiromichi Fujie
Keyword(s):  
Articular Cartilage ◽  
Superficial Layer ◽  
Cell Delivery ◽  
Compressive Property ◽  
Chondral Defect ◽  
Element Analysis ◽  
Normal Cartilage ◽  
Cell Based Therapy ◽  
Immunological Effects

Since the healing capacity of articular cartilage is limited, it is important to develop cell-based therapies for the repair of cartilage. Although synthetic or animal-derived scaffolds are frequently used for effective cell delivery long-term safety and efficiency of such scaffolds still remain unclear. We have been studying on a scaffold-free tissue engineered construct (TEC) bio-synthesized from synovium-derived mesenchymal stem cells (MSCs) [1]. As the TEC specimen is composed of cells with their native extracellular matrix, we believe that it is free from concern regarding long term immunological effects. our previous studies indicated that a porcine partial thickness chondral defect was successfully repaired with TEC but that the compressive property of the TEC-treated cartilage-like repaired tissue was different from normal cartilage in both immature and mature animals. Imura et al. found that the permeability of the immature porcine cartilage-like tissues repaired with TEC recovered to normal level for 6 months except the superficial layer [2]. Therefore, the present study was performed to determine the depth-dependent permeability of mature porcine cartilage-like tissue repaired with TEC. Moreover, we investigated the effect of difference of permeability on the compressive property of articular cartilage using a finite element analysis (FEM).

scholarly journals Optical Biomarkers for the Diagnosis of Osteoarthritis through Raman Spectroscopy: Radiological and Biochemical Validation Using Ex Vivo Human Cartilage Samples

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 546
Author(s):  
Paula Casal-Beiroa ◽  
Vanesa Balboa-Barreiro ◽  
Natividad Oreiro ◽  
Sonia Pértega-Díaz ◽  
Francisco J. Blanco ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Articular Cartilage ◽  
Ex Vivo ◽  
Cartilage Degradation ◽  
Calcium Pyrophosphate ◽  
Calcium Pyrophosphate Dihydrate ◽  
Label Free ◽  
Molecular Fingerprint ◽  
Human Cartilage ◽  
Biochemical Validation

Osteoarthritis (OA) is the most common rheumatic disease, characterized by progressive articular cartilage degradation. Raman spectroscopy (RS) has been recently proposed as a label-free tool to detect molecular changes in musculoskeletal tissues. We used cartilage samples derived from human femoral heads to perform an ex vivo study of different Raman signals and ratios, related to major and minor molecular components of articular cartilage, hereby proposed as candidate optical biomarkers for OA. Validation was performed against the radiological Kellgren–Lawrence (K-L) grading system, as a gold standard, and cross-validated against sulfated glycosaminoglycans (sGAGs) and total collagens (Hyp) biochemical contents. Our results showed a significant decrease in sGAGs (SGAGs, A1063 cm−1/A1004 cm−1) and proteoglycans (PGs, A1375 cm−1/A1004 cm−1) and a significant increase in collagen disorganization (ColD/F, A1245 cm−1/A1270 cm−1), with OA severity. These were correlated with sGAGs or Hyp contents, respectively. Moreover, the SGAGs/HA ratio (A1063 cm−1/A960 cm−1), representing a functional matrix, rich in proteoglycans, to a mineralized matrix-hydroxyapatite (HA), was significantly lower in OA cartilage (K-L I vs. III–IV, p < 0.05), whilst the mineralized to collagenous matrix ratio (HA/Col, A960 cm−1/A920 cm−1) increased, being correlated with K-L. OA samples showed signs of tissue mineralization, supported by the presence of calcium crystals-related signals, such as phosphate, carbonate, and calcium pyrophosphate dihydrate (MGP, A960 cm−1/A1004 cm−1, MGC, A1070 cm−1/A1004 cm−1 and A1050 cm−1/A1004 cm−1). Finally, we observed an increase in lipids ratio (IL, A1450 cm−1/A1670 cm−1) with OA severity. As a conclusion, we have described the molecular fingerprint of hip cartilage, validating a panel of optical biomarkers and the potential of RS as a complementary diagnostic tool for OA.

scholarly journals New Therapeutic Strategies for Osteoarthritis by Targeting Sialic Acid Receptors

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 637 ◽  
Author(s):  
Paula Carpintero-Fernandez ◽  
Marta Varela-Eirin ◽  
Alessandra Lacetera ◽  
Raquel Gago-Fuentes ◽  
Eduardo Fonseca ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Ex Vivo ◽  
Molecular Model ◽  
Cartilage Degradation ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Novel Therapy ◽  
Human Cartilage ◽  
Sialic Acid Receptors ◽  
Cartilage Breakdown

Osteoarthritis (OA) is the most common degenerative joint disease characterized by articular cartilage degradation and joint degeneration. The articular cartilage is mainly formed by chondrocytes and a collagen-proteoglycan extracellular matrix that contains high levels of glycosylated proteins. It was reported that the shift from glycoproteins containing α-2,6-linked sialic acids to those that contain α-2,3 was associated with the onset of common types of arthritis. However, the pathophysiology of α-2,3-sialylation in cartilage has not been yet elucidated. We show that cartilage from osteoarthritic patients expresses high levels of the α-2,3-sialylated transmembrane mucin receptor, known as podoplanin (PDPN). Additionally, the Maackia amurensis seed lectin (MASL), that can be utilized to target PDPN, attenuates the inflammatory response mediated by NF-kB activation in primary chondrocytes and protects human cartilage breakdown ex vivo and in an animal model of arthritis. These findings reveal that specific lectins targeting α-2,3-sialylated receptors on chondrocytes might effectively inhibit cartilage breakdown. We also present a computational 3D molecular model for this interaction. These findings provide mechanistic information on how a specific lectin could be used as a novel therapy to treat degenerative joint diseases such as osteoarthritis.

scholarly journals Stromal-Vascular Fraction and Adipose-derived Stem Cell Therapies Improve Cartilage Regeneration in Osteoarthritis-induced Rats

2021 ◽  
Author(s):  
Wan-Ting Yang ◽  
Chun-Yen Ke ◽  
Kuang-Ting Yeh ◽  
Shyh-Geng Huang ◽  
Zi-Yang Lin ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Knee Joint ◽  
Stromal Vascular Fraction ◽  
Cartilage Regeneration ◽  
Left Knee ◽  
Cartilage Injury ◽  
Cell Therapies ◽  
Cell Counts ◽  
White Blood Cell Counts ◽  
Adipose Derived Stem Cell

Abstract BackgroundThis study evaluated the effects of the stromal vascular fraction (SVF) and adipose-derived stem cells (ADSCs) on cartilage injury in an osteoarthritis (OA) rat model. MethodsSodium iodoacetate (3 mg/50 μL) was used to induce OA in the left knee joint of rats. On day 14 after OA induction, 50 μL of SVF (5 × 106 cells), ADSCs (1 × 106 cells), or 0.9% normal saline (NS) was injected into the left knee-joint cavity of each group. ResultsA macroscopic view of the articular cartilage revealed a damaged, concave, and inflamed appearance in the NS group. Histological sections revealed that the cartilage in the NS group was uneven and thin and had hyperchromatic cell infiltration. Notably, the conditions of articular cartilages improved on day 7 after the SVF and ADSC treatments. Furthermore, the cartilage surface had recovered to nearly normal and appeared smooth and bright on day 14 in the SVF and ADSC groups, and a thick cartilage layer was observed on histology. Additionally, the white blood cell counts in the SVF and ADSC groups were higher than those in the NS group on day 14. Plasma IL-1β levels on days 7 and 14 were reduced in the SVF and ADSC groups. ConclusionThese results indicated that both SVF and ADSC treatments may assist in articular cartilage regeneration after cartilage injury. Cell therapy may benefit patients with OA. However, clinical trials with humans are required before the application of SVF and ADSC treatments in patients with OA.

scholarly journals Mesenchymal Stem Cells: Current Concepts in the Management of Inflammation in Osteoarthritis

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 785
Author(s):  
Asma Abdullah Nurul ◽  
Maryam Azlan ◽  
Muhammad Rajaei Ahmad Mohd Zain ◽  
Alphy Alphonsa Sebastian ◽  
Ying Zhen Fan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Current Knowledge ◽  
Cartilage Regeneration ◽  
Joint Inflammation ◽  
Symptomatic Treatment ◽  
Cell Based Therapy ◽  
Ability To Regenerate ◽  
Primary Focus

Osteoarthritis (OA) has traditionally been known as a “wear and tear” disease, which is mainly characterized by the degradation of articular cartilage and changes in the subchondral bone. Despite the fact that OA is often thought of as a degenerative disease, the catabolic products of the cartilage matrix often promote inflammation by activating immune cells. Current OA treatment focuses on symptomatic treatment, with a primary focus on pain management, which does not promote cartilage regeneration or attenuate joint inflammation. Since articular cartilage have no ability to regenerate, thus regeneration of the tissue is one of the key targets of modern treatments for OA. Cell-based therapies are among the new therapeutic strategies for OA. Mesenchymal stem cells (MSCs) have been extensively researched as potential therapeutic agents in cell-based therapy of OA due to their ability to differentiate into chondrocytes and their immunomodulatory properties that can facilitate cartilage repair and regeneration. In this review, we emphasized current knowledge and future perspectives on the use of MSCs by targeting their regeneration potential and immunomodulatory effects in the treatment of OA.

scholarly journals Ex Vivo Systems to Study Chondrogenic Differentiation and Cartilage Integration

2021 ◽  
Vol 6 (1) ◽  
pp. 6
Author(s):  
Graziana Monaco ◽  
Alicia J. El Haj ◽  
Mauro Alini ◽  
Martin J. Stoddart
Keyword(s):  
Articular Cartilage ◽  
Chondrogenic Differentiation ◽  
Ex Vivo ◽  
Cartilage Regeneration ◽  
Therapeutic Interventions ◽  
Surrounding Tissue ◽  
Self Healing ◽  
Culture Models ◽  
Articular Cartilage Injury ◽  
Cartilage Integration

Articular cartilage injury and repair is an issue of growing importance. Although common, defects of articular cartilage present a unique clinical challenge due to its poor self-healing capacity, which is largely due to its avascular nature. There is a critical need to better study and understand cellular healing mechanisms to achieve more effective therapies for cartilage regeneration. This article aims to describe the key features of cartilage which is being modelled using tissue engineered cartilage constructs and ex vivo systems. These models have been used to investigate chondrogenic differentiation and to study the mechanisms of cartilage integration into the surrounding tissue. The review highlights the key regeneration principles of articular cartilage repair in healthy and diseased joints. Using co-culture models and novel bioreactor designs, the basis of regeneration is aligned with recent efforts for optimal therapeutic interventions.

scholarly journals Stromal-Vascular Fraction and Adipose-Derived Stem Cell Therapies Improve Cartilage Regeneration in Osteoarthritis-Induced Rats

2021 ◽  
Author(s):  
Wan-Ting Yang ◽  
Chun-Yen Ke ◽  
Kuang-Ting Yeh ◽  
Shyh-Geng Huang ◽  
Zi-Yang Lin ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Knee Joint ◽  
Stromal Vascular Fraction ◽  
Cartilage Regeneration ◽  
Left Knee ◽  
Cartilage Injury ◽  
Cell Therapies ◽  
Cell Counts ◽  
White Blood Cell Counts ◽  
Adipose Derived Stem Cell

Abstract This study aimed to evaluated the effects of the stromal vascular fraction (SVF) and adipose-derived stem cells (ADSCs) on cartilage injury in an osteoarthritis (OA) rat model. Sodium iodoacetate (3mg/50µL) was used to induce OA in the left knee joint of rats. On day 14 after OA induction, 50µL of SVF(5×106cells), ADSCs(1×106cells), or 0.9% normal saline (NS) was injected into the left knee-joint cavity of each group. The macroscopic view and histological sections revealed that the articular cartilage in the NS group were damaged, inflamed, uneven and thin, and had hyperchromatic cell infiltration. Notably, the cartilage surface had recovered to nearly normal and appeared smooth and bright on day 14 in the SVF and ADSC groups. Additionally, the white blood cell counts in the SVF and ADSC groups were higher than those in the NS group on day 14. Plasma IL-1β levels on days 7 and 14 were reduced in the SVF and ADSC groups. These results indicated that both SVF and ADSC treatments may assist in articular cartilage regeneration after cartilage injury. Cell therapy may benefit patients with OA. However, clinical trials with humans are required before the application of SVF and ADSC treatments in patients with OA.

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.

Targeted cell delivery for articular cartilage regeneration and osteoarthritis treatment

2019 ◽  
Vol 24 (11) ◽  
pp. 2212-2224 ◽  
Author(s):  
Nahid Nasiri ◽  
Samaneh Hosseini ◽  
Mauro Alini ◽  
Ali Khademhosseini ◽  
Mohamadreza Baghaban Eslaminejad
Keyword(s):  
Articular Cartilage ◽  
Cartilage Regeneration ◽  
Cell Delivery ◽  
Osteoarthritis Treatment ◽  
Articular Cartilage Regeneration

Progenitor Cells in Healthy and Osteoarthritic Human Cartilage Have Extensive Culture Expansion Capacity while Retaining Chondrogenic Properties

Cartilage ◽  
2021 ◽  
pp. 194760352110596
Author(s):  
M. Rikkers ◽  
J.V. Korpershoek ◽  
R. Levato ◽  
J. Malda ◽  
L.A. Vonk
Keyword(s):  
Articular Cartilage ◽  
Progenitor Cells ◽  
Cartilage Regeneration ◽  
Surface Marker ◽  
Type I ◽  
Human Articular Cartilage ◽  
Human Cartilage ◽  
Promising Alternative ◽  
Surface Marker Expression ◽  
Marker Expression

Objective Articular cartilage-derived progenitor cells (ACPCs) are a potential new cell source for cartilage repair. This study aims to characterize endogenous ACPCs from healthy and osteoarthritic (OA) cartilage, evaluate their potential for cartilage regeneration, and compare this to cartilage formation by chondrocytes. Design ACPCs were isolated from full-thickness healthy and OA human cartilage and separated from the total cell population by clonal growth after differential adhesion to fibronectin. ACPCs were characterized by growth kinetics, multilineage differentiation, and surface marker expression. Chondrogenic redifferentiation of ACPCs was compared with chondrocytes in pellet cultures. Pellets were assessed for cartilage-like matrix production by (immuno)histochemistry, quantitative analyses for glycosaminoglycans and DNA content, and expression of chondrogenic and hypertrophic genes. Results Healthy and OA ACPCs were successfully differentiated toward the adipogenic and chondrogenic lineage, but failed to produce calcified matrix when exposed to osteogenic induction media. Both ACPC populations met the criteria for cell surface marker expression of mesenchymal stromal cells (MSCs). Healthy ACPCs cultured in pellets deposited extracellular matrix containing proteoglycans and type II collagen, devoid of type I collagen. Gene expression of hypertrophic marker type X collagen was lower in healthy ACPC pellets compared with OA pellets. Conclusions This study provides further insight into the ACPC population in healthy and OA human articular cartilage. ACPCs show similarities to MSCs, yet do not produce calcified matrix under well-established osteogenic culture conditions. Due to extensive proliferative potential and chondrogenic capacity, ACPCs show potential for cartilage regeneration and possibly for clinical application, as a promising alternative to MSCs or chondrocytes.

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