scholarly journals Human Suprapatellar Fat Pad-Derived Mesenchymal Stem Cells Induce Chondrogenesis and Cartilage Repair in a Model of Severe Osteoarthritis

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Ignacio Muñoz-Criado ◽  
Jose Meseguer-Ripolles ◽  
Maravillas Mellado-López ◽  
Ana Alastrue-Agudo ◽  
Richard J Griffeth ◽  
...  
Keyword(s):  
Cartilage Regeneration ◽  
Cartilage Degeneration ◽  
Population Doubling ◽  
Control Group ◽  
Fat Pad ◽  
Joint Implant ◽  
Adipose Derived Stem Cell ◽  
And Cartilage ◽  
Fat Pads

Cartilage degeneration is associated with degenerative bone and joint processes in severe osteoarthritis (OA). Spontaneous cartilage regeneration is extremely limited. Often the treatment consists of a partial or complete joint implant. Adipose-derived stem cell (ASC) transplantation has been shown to restore degenerated cartilage; however, regenerative differences of ASC would depend on the source of adipose tissue. The infra- and suprapatellar fat pads surrounding the knee offer a potential autologous source of ASC for patients after complete joint substitution. When infrapatellar- and suprapatellar-derived stromal vascular fractions (SVF) were compared, a significantly higher CD105 (+) population was found in the suprapatellar fat. In addition, the suprapatellar SVF exhibited increased numbers of colony formation units and a higher population doubling in culture compared to the infrapatellar fraction. Both the suprapatellar- and infrapatellar-derived ASC were differentiated in vitro into mature adipocytes, osteocytes, and chondrocytes. However, the suprapatellar-derived ASC showed higher osteogenic and chondrogenic efficiency. Suprapatellar-derived ASC transplantation in a severe OA mouse model significantly diminished the OA-associated knee inflammation and cartilage degenerative grade, significantly increasing the production of glycosaminoglycan and inducing endogenous chondrogenesis in comparison with the control group. Overall, suprapatellar-derived ASC offer a potential autologous regenerative treatment for patients with multiple degenerative OA.

Culture Expanded Canine Mesenchymal Stem Cells Possess Osteochondrogenic Potential in Vivo and in Vitro

1997 ◽  
Vol 6 (2) ◽  
pp. 125-134 ◽  
Author(s):  
S. Kadiyala ◽  
R. G. Young ◽  
M. A. Thiede ◽  
S. P. Bruder
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Morphological Characteristics ◽  
Cartilage Regeneration ◽  
Population Doubling ◽  
Population Doubling Time ◽  
Human Mscs ◽  
And Cartilage

Mesenchymal Stem Cells (MSCs) possessing the capacity to differentiate into various cell types such as osteoblasts, chondrocytes, myoblasts, and adipocytes have been previously isolated from the marrow and periosteum of human, murine, lapine, and avian species. This study documents the existence of similar multipotential stem cells in canine marrow. The cells were isolated from marrow aspirates using a modification of techniques previously established for human MSCs (hMSCs), and found to possess similar growth and morphological characteristics, as well as osteochondrogenic potential in vivo and in vitro. On the basis of these results, the multipotential cells that were isolated and culture expanded are considered to be canine MSCs (cMSCs). The occurrence of cMSCs in the marrow was determined to be one per 2.5 × 104 nucleated cells. After enrichment of the cMSCs by centrifugation on a Per-coll cushion, the cells were cultivated in selected lots of serum. Like the hMSCs, cMSCs grew as colonies in primary culture and on replating, grew as a monolayer culture with very uniform spindle morphology. The population doubling time for these cMSCs was approximately 2 days. The morphology and the growth kinetics of the cMSCs were retained following repeated passaging. The osteogenic phenotype could be induced in the cMSC cultures by the addition of a synthetic glucocorticoid, dexamethasone. In these osteogenic cultures, alkaline phosphatase activity was elevated up to 10-fold, and mineralized matrix production was evident. When cMSCs were loaded onto porous ceramics and implanted in autologous canine or athymic murine hosts, copious amounts of bone and cartilage were formed in the pores of the implants. The MSC-mediated osteogenesis obtained by the implantation of the various MSC-loaded matrix combinations is the first evidence of osteogenesis in a canine model by implantation of culture expanded autologous stem cells. The identification and isolation of cMSCs now makes it feasible to pursue preclinical models of bone and cartilage regeneration in canine hosts.

Kartogenin mediates cartilage regeneration via stimulating the IL-6/Stat3-dependent proliferation of cartilage stem/progenitor cells

2020 ◽  
Author(s):  
Tao Liu ◽  
Xiaolin Li ◽  
Ting Wang ◽  
Shuai Zhang ◽  
Yanxia Zhu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Progenitor Cells ◽  
Cartilage Regeneration ◽  
Cartilage Degeneration ◽  
Control Group ◽  
Joint Injury ◽  
M Phase ◽  
Knee Joint Injury

Abstract Background: Declination of endogenous stem cells in cartilage is regarded as the cause of cartilage degeneration. Kartogenin (KGN) is well known to play an important role in chondrogenesis of mesenchymal stem cells (MSC).Methods: Using MSCs isolated from rat cartilages, we analyzed the changing of transcriptomics after the treatment of KGN in vitro. DMM animal models were then applied to identified the effect of MSCs proliferation in vivo after KGN capsule injection. Furthermore, we explored the potential mechanisms how KGN mediates cartilage regeneration and proliferation of cartilage progenitor cells.Results: In this study, we demonstrate that KGN can promote the proliferation of MSC from cartilage, respectively. The percentage of G2-M phase cells in culture reached over 10%, nearly twice as the control group with KGN treatment. Transcriptomic profiling of rat cartilage stem/progenitor cells (CSPC) revealed that the expression of at least 20 cell cycle related genes was significantly changed in response to the KGN treatment. IL-6 and its co-receptor Gp130 gene expression level are much higher than the untreated control. The phosphorylation of the IL-6-downstreamt molecular Stat-3 was enhanced upon the KGN stimulation. The knee joint injury animal model further showed the increased articular cartilage thickness after KGN treatment. Interestingly, the IHC staining also demonstrated the up-regulated level of Stat-3 phosphorylation and enhanced distribution of CD44+/CD105+ cells in the KGN-treated cartilage.Conclusion: Taken together, our data suggest that KGN promotes cartilage regeneration at least partially by stimulating the IL-6/Stat3-dependent proliferation of stem cells resident in the cartilage.

scholarly journals Early patellofemoral articular cartilage degeneration in a rat model of patellar instability is associated with activation of the NF-κB signaling pathway

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Wei Lin ◽  
Huijun Kang ◽  
Yike Dai ◽  
Yingzhen Niu ◽  
Guangmin Yang ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Signaling Pathway ◽  
Subchondral Bone ◽  
Patellofemoral Joint ◽  
Patellar Instability ◽  
Cartilage Degeneration ◽  
Control Group ◽  
And Control ◽  
Articular Cartilage Degeneration ◽  
And Cartilage

Abstract Background Patellar instability (PI) often increases the possibility of lateral patellar dislocation and early osteoarthritis. The molecular mechanism of early articular cartilage degeneration during patellofemoral osteoarthritis (PFOA) still requires further investigation. However, it is known that the NF-κB signaling pathway plays an important role in articular cartilage degeneration. The aim of this study was to investigate the relationship between the NF-κB signaling pathway and patellofemoral joint cartilage degeneration. Methods We established a rat model of PI-induced PFOA. Female 4-week-old Sprague-Dawley rats (n = 120) were randomly divided into two groups: the PI (n = 60) and control group (n = 60). The distal femurs of the PI and control group were isolated and compared 4, 8, and 12 weeks after surgery. The morphological structure of the trochlear cartilage and subchondral bone were evaluated by micro-computed tomography and histology. The expression of NF-κB, matrix metalloproteinase (MMP)-13, collagen X, and TNF-ɑ were evaluated by immunohistochemistry and quantitative polymerase chain reaction. Results In the PI group, subchondral bone loss and cartilage degeneration were found 4 weeks after surgery. Compared with the control group, the protein and mRNA expression of NF-κB and TNF-ɑ were significantly increased 4, 8, and 12 weeks after surgery in the PI group. In addition, the markers of cartilage degeneration MMP-13 and collagen X were more highly expressed in the PI group compared with the control group at different time points after surgery. Conclusions This study has demonstrated that early patellofemoral joint cartilage degeneration can be caused by PI in growing rats, accompanied by significant subchondral bone loss and cartilage degeneration. In addition, the degeneration of articular cartilage may be associated with the activation of the NF-κB signaling pathway and can deteriorate with time as a result of PI.

scholarly journals Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuzhao Huang ◽  
Yuchen He ◽  
Meagan J. Makarcyzk ◽  
Hang Lin
Keyword(s):  
Untreated Control ◽  
Cell Number ◽  
Cartilage Tissue ◽  
Population Doubling ◽  
Control Group ◽  
Chondrocyte Implantation ◽  
Cartilage Injuries ◽  
Pre Treatment ◽  
Articular Cartilage Injuries

Autologous chondrocyte implantation (ACI) is a procedure used to treat articular cartilage injuries and prevent the onset of post-traumatic osteoarthritis. In vitro expansion of chondrocytes, a necessary step in ACI, results in the generation of senescent cells that adversely affect the quality and quantity of newly formed cartilage. Recently, a senolytic peptide, fork head box O transcription factor 4-D-Retro-Inverso (FOXO4-DRI), was reported to selectively kill the senescent fibroblasts. In this study, we hypothesized that FOXO4-DRI treatment could remove the senescent cells in the expanded chondrocytes, thus enhancing their potential in generating high-quality cartilage. To simulate the in vitro expansion for ACI, chondrocytes isolated from healthy donors were expanded to population doubling level (PDL) 9, representing chondrocytes ready for implantation. Cells at PDL3 were also used to serve as the minimally expanded control. Results showed that the treatment of FOXO4-DRI removed more than half of the cells in PDL9 but did not significantly affect the cell number of PDL3 chondrocytes. Compared to the untreated control, the senescence level in FOXO4-DRI treated PDL9 chondrocytes was significantly reduced. Based on the result from standard pellet culture, FOXO4-DRI pre-treatment did not enhance the chondrogenic potential of PDL9 chondrocytes. However, the cartilage tissue generated from FOXO4-DRI pretreated PDL9 cells displayed lower expression of senescence-relevant secretory factors than that from the untreated control group. Taken together, FOXO4-DRI is able to remove the senescent cells in PDL9 chondrocytes, but its utility in promoting cartilage formation from the in vitro expanded chondrocytes needs further investigation.

scholarly journals Progress and Applications of Polyphosphate in Bone and Cartilage Regeneration

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Yan Wang ◽  
Min Li ◽  
Pei Li ◽  
Haijun Teng ◽  
Dehong Fan ◽  
...  
Keyword(s):  
Cartilage Regeneration ◽  
High Energy ◽  
Cartilage Defects ◽  
Artificial Bone ◽  
Cellular Mechanisms ◽  
Inorganic Polyphosphate ◽  
Morphogenetic Effects ◽  
And Cartilage

Patients with bone and cartilage defects due to infection, tumors, and trauma are quite common. Repairing bone and cartilage defects is thus a major problem for clinicians. Autologous and artificial bone transplantations are associated with many challenges, such as limited materials and immune rejection. Bone and cartilage regeneration has become a popular research topic. Inorganic polyphosphate (polyP) is a widely occurring biopolymer with high-energy phosphoanhydride bonds that exists in organisms from bacteria to mammals. Much data indicate that polyP acts as a regulator of gene expression in bone and cartilage tissues and exerts morphogenetic effects on cells involved in bone and cartilage formation. Exposure of these cells to polyP leads to the increase of cytokines that promote the differentiation of mesenchymal stem cells into osteoblasts, accelerates the osteoblast mineralization process, and inhibits the differentiation of osteoclast precursors to functionally active osteoclasts. PolyP-based materials have been widely reported in in vivo and in vitro studies. This paper reviews the current cellular mechanisms and material applications of polyP in bone and cartilage regeneration.

Dexamethasone induces apoptosis in proliferative canine tendon cells and chondrocytes

2008 ◽  
Vol 21 (04) ◽  
pp. 337-342 ◽  
Author(s):  
M. A. Hossain ◽  
J. Park ◽  
S. H. Choi ◽  
G. Kim
Keyword(s):  
Cell Proliferation ◽  
Cartilage Degeneration ◽  
Dependent Manner ◽  
Tendon Cells ◽  
Cartilage Cells ◽  
In Vitro Effects ◽  
Nuclear Apoptosis ◽  
And Cartilage

SummaryDexamethasone (Dexa) has been commonly used in humans and domestic animals, particularly in the treatment of tendon injuries and cartilage degeneration. However, it is often associated with tendon rupture and impaired tendon and cartilage healing. In the present study, we investigated Dexa’s in vitro effects on the growth of cell proliferation and the induction of apoptosis in canine Achilles tendon cells and chondrocytes. Cell proliferation after treatment with Dexa for two to six days was quantified by a 2,3-bis{2-methoxy- 4-nitro-5-sulfophenyl}-2H-tetrazolium-5-carboxyanilide inner salt assay (XTT). The results showed that Dexa could inhibit the proliferation of tendon cells and chondrocytes at increasing concentrations (0.1–50 μg/ml) compared with untreated cells. Cell apoptosis was induced by Dexa, as evidenced by the typical nuclear apoptosis using Hoechst 33258 staining. Dexa increased the apoptosis of canine tendon cells and chondrocytes in a time-dependent manner. In canine tendon cells and chondrocytes that were treated with 25 and 50 μg/ml concentration of Dexa, the number of condensed apoptotic nuclei was significantly increased. In addition, culturing with Dexa and the glucocorticoid receptor blocker, mifepristone, significantly arrested apoptosis of tendon cells and chondrocytes. Based on our in vitro data, we hypothesized that in vivo treatment with glucocorticoids may diminish the proliferation of tendon and cartilage cells by increasing apoptosis and suppressing the proliferation. Our findings suggest that Dexa could be used with caution in dogs with articular or tendon problems.

Arg-Gly-Asp Peptide-Functionalized Superparamagnetic γ-Fe2O3 Nanoparticles Enhance Osteoblast Migration In Vitro

2020 ◽  
Vol 20 (10) ◽  
pp. 6173-6179
Author(s):  
Xue Liu ◽  
Xiao-Ling Yang ◽  
Qiao Hu ◽  
Mao-Shi Liu ◽  
Tao Peng ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Cell Therapy ◽  
Bone Repair ◽  
Cartilage Regeneration ◽  
Uniform Size ◽  
Low Cytotoxicity ◽  
The Magnetic Field ◽  
And Cartilage ◽  
Osteoblast Migration

Making osteoblast migration manageably target to injury sites has been the key challenging in cell therapy for bone and cartilage regeneration. Superparamagnetic materials, the magnetic guide for cell migration, have been applied to increase cell retention. However, additional targeting modifications are still needed to accelerate the low uptake efficiency and moving speed. Arg-Gly-Asp peptide (RGD)-functionalized magnetic nanoparticles showed cutting-edge competence in cell differentiation control and targeted drug delivery. However, more evidence was required to corroborate its role in osteoblast migration in bone repair. In the present study, RGD-modified γ-Fe2O3 nanoparticles (RGD-Fe2O3 NPs) were prefabricated with the grafting ratio of 33.3–37.4%. The RGD-Fe2O3 NPs unveiled excellent water dispersibility with uniform size distribution at 5–6 nm and negligibly low cytotoxicity. As a result, MC3T3-E1 osteoblasts treated with RGD-Fe2O3 NPs boosted its migration speed in a magnetic field compared with those incubated with unmodified Fe2O3 NPs. Furthermore, osteoblasts treated with RGD-Fe2O3 NPs exhibited more Fe uptake. The results exposed the fact that RGD-mediated specific cellular uptake presented higher efficiency than the non-RGD-mediated one, resulting from a stronger superparamagnetic force between the labeled cells and the magnetic field. These findings indicate that the RGD-functionalized Fe2O3 NPs can promote osteoblast migration in the magnetic field, providing a promising strategy in magnet-guided cell therapy for bone and cartilage regeneration.

scholarly journals Platelet Microparticles Accelerate Proliferation and Growth of Mesenchymal Stem Cells through Longevity-Related Genes

2021 ◽  
Vol 24 (8) ◽  
pp. 607-614
Author(s):  
Maryam Samareh Salavati Pour ◽  
Fatemeh Hoseinpour Kasgari ◽  
Alireza Farsinejad ◽  
Ahmad Fatemi ◽  
Gholamhossein Hassanshahi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Real Time ◽  
Real Time Pcr ◽  
Treated Group ◽  
Population Doubling ◽  
Control Group ◽  
Population Doubling Time ◽  
Longevity Genes

Background: Due to their self-renewal and differentiation ability, the mesenchymal stem cells (MSCs) have been studied extensively. However, the MSCs lifespan is restricted; they undergo several divisions in vitro that cause several alternations in cellular features and relatively lessens their application. Thus, this study was aimed to assess the effect of platelet-derived microparticles (PMPs), a valuable source of proteins, microRNAs (miRNAs), and growth factors, on the expression of hTERT, c-MYC, p16, p53, and p21 as the most important aging and cell longevity genes alongside with population doubling time (PDT) of PMP-treated cells in comparison to a control group. Methods: Umbilical cord MSCs (UC-MSCs) were used in this study, whereby they reached a confluency of 30%. MSCs were treated by PMPs (50 µg/mL), and then, PDT was determined for both groups. Quantitative expression of hTERT, c-MYC, p16, p53, and p21 was examined through quantitative real-time PCR at various intervals (i.e. after five and thirty days as well as freezing-thawing process). Results: Our results demonstrated that the treated group had a shorter PDT in comparison to the control group (P<0.050). The real-Time PCR data also indicated that PMPs were able to remarkably up-regulate hTERT and c-MYC genes expression while down-regulating the expression of p16, p21, and p53 genes (P<0.050), especially following five days of treatment. Conclusion: According to these data, it appears that PMPs are a safe and effective candidate for prolonging the lifespan of UC-MSCs; however, further investigations are needed to corroborate this finding.

A Quantitative Assessment of the Subchondral Changes in Osteoarthritis and its Association to the Cartilage Degeneration

1993 ◽  
Vol 06 (04) ◽  
pp. 198-201 ◽  
Author(s):  
E. Svalastoga ◽  
H. Strøm
Keyword(s):  
Trabecular Bone ◽  
Weight Bearing ◽  
Cartilage Degeneration ◽  
Control Group ◽  
Grading System ◽  
Cartilage Lesions ◽  
Femoral Heads ◽  
Percentage Volume ◽  
Trabecular Bone Area ◽  
And Cartilage

SummaryIn order to quantify the alterations in subchrondral bone and to compare the changes with the severity of the cartilage lesions, a quantitative histological analysis of articular cartilage and subchrondral bone from osteoarthritic and normal femoral heads was performed.The analyses were based on 12 femoral heads, seven which were osteoarthritic and five controls. Coronal sections were made and divided into four separate sites to include two weight-bearing and two non-weight-bearing. For each area the percentage volume of trabecular bone was determined by histomorphometry and the degree of cartilage degeneration was evaluated according to a histologicalhistochemical grading system.The data obtained showed wide variations from site to site, in osteoarthritic femoral heads, with consistently more pronounced alterations in cartilage and subchrondral bone in the weight-bearing areas. Bone thickening and cartilage degeneration were distinctly increased in osteoarthritic joints, in contrast to the control group. By comparing the bony changes with the severity of the cartilage lesions, a correlation of moderate significance was found between the degeneration of the cartilage and sclerosis of the subchrondral bone.Sections from osteoarthritic and normal canine femoral heads were obtained and divided into weight-bearing and non-weight-bearing areas. The trabecular bone area (%) and the severity of cartilage degeneration were determined by bone histo-morphology and a cartilage histological-histochemical grading system.Bone thickening and cartilage degeneration were increased in osteoarthritic joints, when compared to normal controls with consistently more pronounced alterations in weight-bearing areas. The severity of the cartilage lesions were found to corre-late with subchrondral bone sclerosis.

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