scholarly journals Physioxia Expanded Bone Marrow Derived Mesenchymal Stem Cells Have Improved Cartilage Repair in an Early Osteoarthritic Focal Defect Model

Biology ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 230
Author(s):  
Girish Pattappa ◽  
Jonas Krueckel ◽  
Ruth Schewior ◽  
Dustin Franke ◽  
Alexander Mench ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cartilage Repair ◽  
Rabbit Model ◽  
Cartilage Regeneration ◽  
Cartilage Defects ◽  
Large Animal ◽  
Large Animal Models ◽  
Early Oa

Focal early osteoarthritis (OA) or degenerative lesions account for 60% of treated cartilage defects each year. The current cell-based regenerative treatments have an increased failure rate for treating degenerative lesions compared to traumatic defects. Mesenchymal stem cells (MSCs) are an alternative cell source for treating early OA defects, due to their greater chondrogenic potential, compared to early OA chondrocytes. Low oxygen tension or physioxia has been shown to enhance MSC chondrogenic matrix content and could improve functional outcomes of regenerative therapies. The present investigation sought to develop a focal early OA animal model to evaluate cartilage regeneration and hypothesized that physioxic MSCs improve in vivo cartilage repair in both, post-trauma and focal early OA defects. Using a rabbit model, a focal defect was created, that developed signs of focal early OA after six weeks. MSCs cultured under physioxia had significantly enhanced in vitro MSC chondrogenic GAG content under hyperoxia with or without the presence of interleukin-1β (IL-1β). In both post-traumatic and focal early OA defect models, physioxic MSC treatment demonstrated a significant improvement in cartilage repair score, compared to hyperoxic MSCs and respective control defects. Future investigations will seek to understand whether these results are replicated in large animal models and the underlying mechanisms involved in in vivo cartilage regeneration.

scholarly journals Xenogenic Implantation of Equine Synovial Fluid-Derived Mesenchymal Stem Cells Leads to Articular Cartilage Regeneration

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Mohammed Zayed ◽  
Steven Newby ◽  
Nabil Misk ◽  
Robert Donnell ◽  
Madhu Dhar
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Articular Cartilage ◽  
Synovial Fluid ◽  
Cartilage Repair ◽  
Cartilage Regeneration ◽  
Large Animal

Horses are widely used as large animal preclinical models for cartilage repair studies, and hence, there is an interest in using equine synovial fluid-derived mesenchymal stem cells (SFMSCs) in research and clinical applications. Since, we have previously reported that similar to bone marrow-derived MSCs (BMMSCs), SFMSCs may also exhibit donor-to-donor variations in their stem cell properties; the current study was carried out as a proof-of-concept study, to compare the in vivo potential of equine BMMSCs and SFMSCs in articular cartilage repair. MSCs from these two sources were isolated from the same equine donor. In vitro analyses confirmed a significant increase in COMP expression in SFMSCs at day 14. The cells were then encapsulated in neutral agarose scaffold constructs and were implanted into two mm diameter full-thickness articular cartilage defect in trochlear grooves of the rat femur. MSCs were fluorescently labeled, and one week after treatment, the knee joints were evaluated for the presence of MSCs to the injured site and at 12 weeks were evaluated macroscopically, histologically, and then by immunofluorescence for healing of the defect. The macroscopic and histological evaluations showed better healing of the articular cartilage in the MSCs’ treated knee than in the control. Interestingly, SFMSC-treated knees showed a significantly higher Col II expression, suggesting the presence of hyaline cartilage in the healed defect. Data suggests that equine SFMSCs may be a viable option for treating osteochondral defects; however, their stem cell properties require prior testing before application.

Repair of Osteochondral Defects With Predifferentiated Mesenchymal Stem Cells of Distinct Phenotypic Character Derived From a Nanotopographic Platform

2020 ◽  
Vol 48 (7) ◽  
pp. 1735-1747
Author(s):  
Yingnan Wu ◽  
Zheng Yang ◽  
Vinitha Denslin ◽  
XiaFei Ren ◽  
Chang Sheng Lee ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Cartilage Regeneration ◽  
Cartilage Tissue ◽  
Cartilage Defects ◽  
Defect Site

Background: Articular cartilage has a zonal architecture and biphasic mechanical properties. The recapitulation of surface lubrication properties with high compressibility of the deeper layers of articular cartilage during regeneration is essential in achieving long-term cartilage integrity. Current clinical approaches for cartilage repair, especially with the use of mesenchymal stem cells (MSCs), have yet to restore the hierarchically organized architecture of articular cartilage. Hypothesis: MSCs predifferentiated on surfaces with specific nanotopographic patterns can provide phenotypically stable and defined chondrogenic cells and, when delivered as a bilayered stratified construct at the cartilage defect site, will facilitate the formation of functionally superior cartilage tissue in vivo. Study Design: Controlled laboratory study. Methods: MSCs were subjected to chondrogenic differentiation on specific nanopatterned surfaces. The phenotype of the differentiated cells was assessed by the expression of cartilage markers. The ability of the 2-dimensional nanopattern-generated chondrogenic cells to retain their phenotypic characteristics after removal from the patterned surface was tested by subjecting the enzymatically harvested cells to 3-dimensional fibrin hydrogel culture. The in vivo efficacy in cartilage repair was demonstrated in an osteochondral rabbit defect model. Repair by bilayered construct with specific nanopattern predifferentiated cells was compared with implantation with cell-free fibrin hydrogel, undifferentiated MSCs, and mixed-phenotype nanopattern predifferentiated MSCs. Cartilage repair was evaluated at 12 weeks after implantation. Results: Three weeks of predifferentiation on 2-dimensional nanotopographic patterns was able to generate phenotypically stable chondrogenic cells. Implantation of nanopatterned differentiated MSCs as stratified bilayered hydrogel constructs improved the repair quality of cartilage defects, as indicated by histological scoring, mechanical properties, and polarized microscopy analysis. Conclusion: Our results indicate that with an appropriate period of differentiation, 2-dimensional nanotopographic patterns can be employed to generate phenotypically stable chondrogenic cells, which, when implanted as stratified bilayered hydrogel constructs, were able to form functionally superior cartilage tissue. Clinical Relevance: Our approach provides a relatively straightforward method of obtaining large quantities of zone-specific chondrocytes from MSCs to engineer a stratified cartilage construct that could recapitulate the zonal architecture of hyaline cartilage, and it represents a significant improvement in current MSC-based cartilage regeneration.

Combined Effects of Bone Marrow-Derived Mesenchymal Stem Cells and PLGA-PEG-PLGA Scaffolds on Repair of Articular Cartilage Defect

2013 ◽  
Vol 815 ◽  
pp. 345-349 ◽  
Author(s):  
Ching Wen Hsu ◽  
Ping Liu ◽  
Song Song Zhu ◽  
Feng Deng ◽  
Bi Zhang
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Growth Factor ◽  
Cartilage Defect ◽  
Cartilage Regeneration ◽  
Tissue Growth ◽  
Cartilage Defects

Here we reported a combined technique for articular cartilage repair, consisting of bone arrow mesenchymal stem cells (BMMSCs) and poly (dl-lactide-co-glycolide-b-ethylene glycol-b-dl-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymers carried with tissue growth factor (TGF-belat1). In the present study, BMMSCs seeded on PLGA-PEG-PLGA with were incubated in vitro, carried or not TGF-belta1, Then the effects of the composite on repair of cartilage defect were evaluated in rabbit knee joints in vivo. Full-thickness cartilage defects (diameter: 5 mm; depth: 3 mm) in the patellar groove were either left empty (n=18), implanted with BMMSCs/PLGA (n=18), TGF-belta1 modified BMMSCs/PLGA-PEG-PLGA. The defect area was examined grossly, histologically at 6, 24 weeks postoperatively. After implantation, the BMMSCs /PLGA-PEG-PLGA with TGF-belta1 group showed successful hyaline-like cartilage regeneration similar to normal cartilage, which was superior to the other groups using gross examination, qualitative and quantitative histology. These findings suggested that a combination of BMMSCs/PLGA-PEG-PLGA carried with tissue growth factor (TGF-belat1) may be an alternative treatment for large osteochondral defects in high loading sites.

scholarly journals Articular chondrocyte derived exosomes promote cartilage differentiation of human umbilical cord mesenchymal stem cells by activation of autophagy

2020 ◽  
Author(s):  
Ke Ma ◽  
Bo Zhu ◽  
Zetao Wang ◽  
Peian Cai ◽  
Mingwei He ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Cartilage Repair ◽  
Chondrogenic Differentiation ◽  
Phenotypic Expression ◽  
Cartilage Regeneration ◽  
Human Umbilical Cord ◽  
Articular Chondrocyte

Abstract Background Umbilical cord mesenchymal stem cells (HUCMSCs)-based therapies were previously predicated in cartilage regeneration due to the chondrogenic potential of MSCs. However, chondrogenic differentiation of HUMSCs is limited by administration of growth factors like TGF-β that may cause cartilage hypertrophy. It has been reported the exosomes could modulate phenotypic expression of stem cells. However, the role of human chondrogenic derived exosomes (C-EXO) in chondrogenic differentiation of HUCMSCs has not been reported. Results In this study, we successfully isolated chondrocyte-derived exosomes (C-EXO) from human multi-finger cartilage and found that C-EXO efficiently promoted the proliferation and chondrogenic differentiation of HUCMSCs, evidenced by highly expressed aggrecan (ACAN), COL2A and SOX-9. Also, the expression of the fibrotic marker, COL1A and hypertrophic marker, COL10, was significantly lower than that induced by TGF-β. In vivo, stimulation of C-EXO accelerated HUCMSCs-mediated cartilage repair in rabbit models. Furthermore, C-EXO led to increasing autophagosomes during the process of chondrogenic differentiation, indicating that C-EXO promoted cartilage regeneration might be through the activation of autophagy. Conclusions This study suggests that C-EXO has an essential role in fostering chondrogenic differentiation and proliferation of HUCMSCs, which may be a stable supply for articular cartilage repair.

scholarly journals Exosomes from Kartogenin-Pretreated Infrapatellar Fat Pad Mesenchymal Stem Cells Enhance Chondrocyte Anabolism and Articular Cartilage Regeneration

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jiahua Shao ◽  
Jun Zhu ◽  
Yi Chen ◽  
Qiwei Fu ◽  
Lexiang Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Cartilage Regeneration ◽  
Infrapatellar Fat Pad ◽  
Cartilage Defects ◽  
Control Group ◽  
Fat Pad ◽  
And Control

Objective. To evaluate the effect of Kartogenin-pretreated exosomes derived from infrapatellar fat pad mesenchymal stem cells on chondrocyte in vitro and articular cartilage regeneration in vivo. Methods. Infrapatellar fat pad mesenchymal stem cells (IPFP-MSCs) were isolated from rabbits to harvest exosomes. After identification of mesenchymal stem cells and exosomes, rabbit chondrocytes were divided into three groups for further treatment: the EXO group (chondrocytes treated with exosomes isolated from infrapatellar fat pad mesenchymal stem cells), KGN-EXO group (chondrocytes treated with exosomes isolated from infrapatellar fat pad mesenchymal stem cells pretreated with KGN), and control group. After processing and proliferation, phenotypic changes of chondrocytes were measured. In the in vivo study, 4 groups of rabbits with articular cartilage injury were treated with KGN-EXO, EXO, IPFP-MSCs, and control. Macroscopic evaluation and histological evaluation were made to figure out the different effects of the 4 groups on cartilage regeneration in vivo. Results. The proliferation rate of chondrocytes in the EXO or KGN-EXO group was significantly higher than that in the control group ( P < 0.05 ). The qRT-PCR results showed that the expression of Sox-9, Aggrecan, and Col II was the highest in the KGN-EXO group compared with the EXO group and the control group ( P < 0.05 ). The results of Western blot were consistent with the results of qRT-PCR. In vivo, the cartilage defects in the KGN-EXO group showed better gross appearance and improved histological score than those in IPFP-MSC groups, EXO groups, and control groups ( P < 0.05 ). At 12 weeks, the defect site in the KGN-EXO group was almost completely repaired with a flat and smooth surface, while a large amount of hyaline cartilage-like structures and no obvious cracks were observed. Conclusion. Our study demonstrates that the exosomes isolated from infrapatellar fat pad mesenchymal stem cells pretreated with KGN have potent ability to induce chondrogenic differentiation of stem cells, effectively promoting the proliferation and the expression of chondrogenic proteins and genes of chondrocytes. The KGN-EXO can also promote the repair of articular cartilage defects more effectively, which can be used as a potential therapeutic method in the future.

scholarly journals Heterogeneity of mesenchymal stem cells in cartilage regeneration: from characterization to application

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Kangkang Zha ◽  
Xu Li ◽  
Zhen Yang ◽  
Guangzhao Tian ◽  
Zhiqiang Sun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Cartilage Damage ◽  
Cartilage Regeneration ◽  
Great Promise ◽  
Traditional Treatment ◽  
Different Types ◽  
Selection Of

AbstractArticular cartilage is susceptible to damage but hard to self-repair due to its avascular nature. Traditional treatment methods are not able to produce satisfactory effects. Mesenchymal stem cells (MSCs) have shown great promise in cartilage repair. However, the therapeutic effect of MSCs is often unstable partly due to their heterogeneity. Understanding the heterogeneity of MSCs and the potential of different types of MSCs for cartilage regeneration will facilitate the selection of superior MSCs for treating cartilage damage. This review provides an overview of the heterogeneity of MSCs at the donor, tissue source and cell immunophenotype levels, including their cytological properties, such as their ability for proliferation, chondrogenic differentiation and immunoregulation, as well as their current applications in cartilage regeneration. This information will improve the precision of MSC-based therapeutic strategies, thus maximizing the efficiency of articular cartilage repair.

scholarly journals Mesenchymal Stem Cells Exhibit Both a Proinflammatory and Anti-Inflammatory Effect on Saccular Aneurysm Formation in a Rabbit Model

2019 ◽  
Vol 2019 ◽  
pp. 1-15
Author(s):  
Michael B. Avery ◽  
Brooke L. Belanger ◽  
Amy Bromley ◽  
Arindom Sen ◽  
Alim P. Mitha
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Rabbit Model ◽  
Potential Interaction ◽  
Allogenic Bone ◽  
Aneurysm Formation ◽  
Vehicle Injection ◽  
Anti Inflammatory

Several studies have demonstrated a potential interaction between mesenchymal stem cells (MSCs) and saccular aneurysms. In this study, we sought to determine whether allogenic bone marrow-derived MSCs had the ability to prevent aneurysm formation in a known rabbit elastase aneurysm model. MSCs were injected intravenously in experimental rabbits at the time of surgical creation and two weeks postcreation and compared with control rabbits receiving vehicle injection. Angiography was used to compare aneurysm measurements four weeks postcreation, and aneurysms were harvested for histological properties. Serum was collected longitudinally to evaluate cytokine alterations. Serum from control animals was also utilized to perform in vitro tests with MSCs to compare the effect of the serologic environment in animals with and without aneurysms on MSC proliferation and cytokine production. While aneurysm morphometric comparisons revealed no differences, significant cytokine alterations were observed in vitro and in vivo, suggesting both anti-inflammatory and proinflammatory processes were occurring in the presence of MSCs. Histological analyses suggested that tunica intima hyperplasia was inhibited in the presence of MSCs.

scholarly journals Adipose-Derived Mesenchymal Stem Cells for the Treatment of Articular Cartilage: A Systematic Review on Preclinical and Clinical Evidence

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Francesco Perdisa ◽  
Natalia Gostyńska ◽  
Alice Roffi ◽  
Giuseppe Filardo ◽  
Maurilio Marcacci ◽  
...  
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Clinical Evidence ◽  
Cartilage Regeneration ◽  
Therapeutic Approaches ◽  
Differentiated Cells ◽  
Cartilage Disease

Among the current therapeutic approaches for the regeneration of damaged articular cartilage, none has yet proven to offer results comparable to those of native hyaline cartilage. Recently, it has been claimed that the use of mesenchymal stem cells (MSCs) provides greater regenerative potential than differentiated cells, such as chondrocytes. Among the different kinds of MSCs available, adipose-derived mesenchymal stem cells (ADSCs) are emerging due to their abundancy and easiness to harvest. However, their mechanism of action and potential for cartilage regeneration are still under investigation, and many other aspects still need to be clarified. The aim of this systematic review is to give an overview ofin vivostudies dealing with ADSCs, by summarizing the main evidence for the treatment of cartilage disease of the knee.

scholarly journals Articular chondrocyte-derived extracellular vesicles promote cartilage differentiation of human umbilical cord mesenchymal stem cells by activation of autophagy

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Ke Ma ◽  
Bo Zhu ◽  
Zetao Wang ◽  
Peian Cai ◽  
Mingwei He ◽  
...  
Keyword(s):  
Stem Cells ◽  
Umbilical Cord ◽  
Extracellular Vesicles ◽  
Chondrogenic Differentiation ◽  
Phenotypic Expression ◽  
Rabbit Model ◽  
Cartilage Regeneration ◽  
Human Umbilical Cord ◽  
Articular Chondrocyte

Abstract Background Umbilical cord mesenchymal stem cell (HUCMSC)-based therapies were previously utilised for cartilage regeneration because of the chondrogenic potential of MSCs. However, chondrogenic differentiation of HUCMSCs is limited by the administration of growth factors like TGF-β that may cause cartilage hypertrophy. It has been reported that extracellular vesicles (EVs) could modulate the phenotypic expression of stem cells. However, the role of human chondrogenic-derived EVs (C-EVs) in chondrogenic differentiation of HUCMSCs has not been reported. Results We successfully isolated C-EVs from human multi-finger cartilage and found that C-EVs efficiently promoted the proliferation and chondrogenic differentiation of HUCMSCs, evidenced by highly expressed aggrecan (ACAN), COL2A, and SOX-9. Moreover, the expression of the fibrotic marker COL1A and hypertrophic marker COL10 was significantly lower than that induced by TGF-β. In vivo, C-EVs induced HUCMSCs accelerated the repair of the rabbit model of knee cartilage defect. Furthermore, C-EVs led to an increase in autophagosomes during the process of chondrogenic differentiation, indicating that C-EVs promote cartilage regeneration through the activation of autophagy. Conclusions C-EVs play an essential role in fostering chondrogenic differentiation and proliferation of HUCMSCs, which may be beneficial for articular cartilage repair.

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