scholarly journals Attenuation of Trauma-induced Osteoarthritis by Repetitive Intra-articular Administration of Peripheral Blood Derived Mesenchymal Stem Cells

2021 ◽  
Author(s):  
Weiping Lin ◽  
Zhengmeng Yang ◽  
Liu Shi ◽  
Haixing Wang ◽  
Qi Pan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Subchondral Bone ◽  
Peripheral Blood ◽  
Cartilage Degradation ◽  
Cartilage Tissue ◽  
Synovial Joint ◽  
Post Surgery ◽  
Sham Surgery

Abstract Background: Osteoarthritis (OA) is a chronic joint disease, characterized by articular cartilage degradation, subchondral bone hardening, and inflammation of the whole synovial joint. There is no pharmacological treatment in slowing down OA progression, leading to costly surgical interventions eventually. Cell therapy using chondrocytes or progenitor cells from different sources has been reported in clinical trials for OA management with some success, but outcomes are varied. Peripheral blood derived mesenchymal stem cells (PB-MSCs) are promising cells owing to their easy collection, superior migration, and differentiation potentials. In the current study, we evaluated the effect of intra-articular administration of PB-MSCs on the progression of OA in mice.Methods: C57BL/6J mice (8-10 weeks old male) were subjected to destabilization of the medial meniscus surgeries (DMM) on their right joints following protocols as previously reported. The mice after DMM were randomly treated with saline (vehicle control), PB-MSCs, or adipose tissue derived MSCs (AD-MSCs) (n = 7 per group). The mice treated with sham surgery were regarded as sham controls (n = 7). PB-MSCs and AD-MSCs were harvested and cultured according to previous published protocols, and pre-labeled with BrdU for 48 h before use. PB-MSCs or AD-MSCs (5 × 105 cells/mouse; passage 3~5) were injected into the right knee joints thrice post-surgery (except sham surgery group). The mice were euthanized at 8 weeks post-surgery and knee joint samples were collected for micro-CT and histological examinations.Results: PB-MSCs administration significantly reduced hardening of subchondral bone comparing to vehicle controls. Safranin O staining showed that PB-MSCs treatment ameliorated degeneration of articular cartilage, which is comparable to AD-MSCs treatment. The expression of catabolic marker MMP13 was significantly reduced in articular cartilage of PB-MSCs-treated groups comparing to vehicle controls. Co-expression of BrdU and Sox9 were detected, indicating injected PB-MSCs differentiated towards chondrocytes in situ. Reduced level of IL-6 in the peripheral sera of PB-MSCs- and AD-MSCs-treated mice was also determined. Conclusions: Repetitive administration of PB-MSCs or AD-MSCs halted OA progression through inhibiting cartilage degradation and inflammation. PB-MSCs may become a promising cell source for cartilage tissue repair and alleviation of OA progression.

Microfluidic Encapsulation of Human Mesenchymal Stem Cells for Articular Cartilage Tissue Regeneration

2017 ◽  
Vol 9 (10) ◽  
pp. 8589-8601 ◽  
Author(s):  
Fanyi Li ◽  
Vinh X. Truong ◽  
Helmut Thissen ◽  
Jessica E. Frith ◽  
John S. Forsythe
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Tissue Regeneration ◽  
Human Mesenchymal Stem Cells ◽  
Cartilage Tissue

scholarly journals Transferring Mesenchymal Stem Cells to the Osteoarthritic Cartilage: Translating Science to Medicine

2020 ◽  
pp. 1-4
Author(s):  
J Agilinko ◽  
J Agilinko ◽  
A Yoong ◽  
Bertrand Agilinko ◽  
Mohammad Hasan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Biological Activities ◽  
Cell Types ◽  
Biomechanical Properties ◽  
Cartilage Tissue ◽  
Rational Approach ◽  
Synovial Joint ◽  
Osteoarthritic Cartilage ◽  
Current Therapies

Osteoarthritis (OA) is associated with loss of the phenotypic stability of affected joints. Due to its avascular nature, biomechanical properties of the cartilage tissue in a synovial joint are particularly compromised as the disease progresses. Current therapies for OA merely buy time until arthrodesis or arthroplasty, the ‘end game’, is ultimately reached. Over the last two decades, promising experimental data has started to emerge on mesenchymal stem cells (MSCs) as candidate cell types for cell and/ or tissue-based cartilage tissue repair. The principal attraction of MSCs lies in their consistent chondrogenic differentiation and proliferative propensities. Practically, they offer ease of isolation and culture-expansion. Targeted gene therapy can further enhance their delivery into osteoarthritic joints. Henceforth, understanding the biological activities and mechanisms of action of MSCs is crucial for a rational approach to their clinical application in osteoarthritic joints.

scholarly journals Characterization of OA development between sexes in the rat medial meniscal transection model

2019 ◽  
Author(s):  
Krishna A. Pucha ◽  
Jay M. McKinney ◽  
Julia M. Fuller ◽  
Nick J. Willett
Keyword(s):  
Articular Cartilage ◽  
Subchondral Bone ◽  
Bone Structure ◽  
Meniscal Tear ◽  
Cartilage Degradation ◽  
Mineral Density ◽  
Male And Female ◽  
Post Surgery ◽  
Medial Meniscal Tear

AbstractObjectiveOsteoarthritis (OA) is a chronic degenerative disease of the joints characterized by articular cartilage degradation. While there are clear sex differences in OA development in humans, most pre-clinical research has been conducted solely in male animals thus limiting the ability of these findings to be generalized to both sexes in the context of this disease. The objective of this study was to determine if sex impacts the progression and severity of OA in the rat medial meniscal tear (MMT) preclinical animal model used to surgically induce OA. It was hypothesized that differences would be observed between males and females following MMT surgery.DesignA MMT model was employed in male and female Lewis rats to induce OA. Animals were euthanized 3 weeks post-surgery and EPIC-μCT was used to quantitatively evaluate articular cartilage structure and composition, osteophyte volumes and subchondral bone structure.ResultsQuantitative analysis of the medial 1/3 articular cartilage via EPIC-μCT showed increased cartilage thickness and proteoglycan loss in the MMT of both sexes, when compared to sham. Additionally, both male and female animals in the MMT group had increased subchondral bone mineral density and larger total osteophyte volumes due to MMT.ConclusionThese data demonstrate that OA can be induced in both sexes using the rat MMT model. Moving forward, adding sex as a factor in preclinical OA studies should be standard practice in pre-clinical studies in order to elucidate more inclusive and translatable results into the clinic.

Overexpressing Runx2 of BMSCs Improves the Repairment of knee Cartilage Defects

2020 ◽  
Vol 20 (5) ◽  
pp. 395-404
Author(s):  
Jing Hu ◽  
Wen-Zhong Zou ◽  
Ling Li ◽  
Zheng-shuai Shi ◽  
Xiang-Zhong Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Joint Fluid ◽  
Cartilage Tissue ◽  
Cell Group ◽  
Knee Cartilage ◽  
Marrow Mesenchymal Stem Cells

Background: Recruitment of gene modifying bone marrow mesenchymal stem cells (BMSCs) has been considered an alternative to single-cell injection in articular cartilage repair. Purpose: This study aimed to investigate whether the effect of runt-related transcription factor 2(Runx2) overexpression bone marrow mesenchymal stem cells in vivo could improve the quality of repaired tissue of a knee cartilage defect in a rabbit model. Methods: Thirty-two New Zealand rabbits were randomly divided into four groups. The blank group (Con) did not receive anything, the model group (Mo) was administered saline, the simple stem cell group (MSCs) received MSCs injection, and the Runx2 transfection group (R-MSCs) received Runx2 overexpression MSCs injection. After adapting to the environment for a week, a 5 mm diameter cylindrical osteochondral defect was created in the center of the medial femoral condyle. Cell and saline injections were performed in the first and third weeks after surgery. The cartilage repair was evaluated by macroscopically and microscopically at 4 and 8 weeks. Results: Macroscopically, defects were filled and surfaces were smoother in the MSCs groups than in the Mo group at 4th week. Microscopically, the R-MSCs group showed coloration similar to surrounding normal articular cartilage tissue at 8 weeks in masson trichrome staining. The COL-II, SOX9, and Aggrecan mRNA expressions of MSCs were enhanced at 4 weeks compared with R-MSCs, then the expression reduced at 8 weeks, but was still higher than Mo group level (P<0.05). The western blot examination revealed that the COL-IIand SOX9 expression of MSCs was higher than R-MSCs at 4 weeks, then the expression reduced at 8 weeks, but was still higher than the Mo level (P<0.05). The IL-1β content in the joint fluid also revealed that cartilage repair with R-MSCs was better than that with MSCs at 8 weeks (P<0.05). Conclusions: The R-MSCs group showed cellular morphology and arrangement similar to surrounding normal articular cartilage tissue, and Runx2 overexpression of MSCs resulted in overall superior cartilage repair as compared with MSCs at 8 weeks.

scholarly journals Osteochondral Regeneration Using Adipose Tissue-Derived Mesenchymal Stem Cells

2020 ◽  
Vol 21 (10) ◽  
pp. 3589 ◽  
Author(s):  
Daiki Murata ◽  
Ryota Fujimoto ◽  
Koichi Nakayama
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Articular Cartilage ◽  
Subchondral Bone ◽  
Three Dimensional ◽  
Cartilage Regeneration ◽  
Joint Disease ◽  
And Function ◽  
Osteochondral Regeneration

Osteoarthritis (OA) is a major joint disease that promotes locomotor deficiency during the middle- to old-age, with the associated disability potentially decreasing quality of life. Recently, surgical strategies to reconstruct both articular cartilage and subchondral bone for OA have been diligently investigated for restoring joint structure and function. Adipose tissue-derived mesenchymal stem cells (AT-MSCs), which maintain pluripotency and self-proliferation ability, have recently received attention as a useful tool to regenerate osteocartilage for OA. In this review, several studies were described related to AT-MSC spheroids, with scaffold and scaffold-free three-dimensional (3D) constructs produced using “mold” or “Kenzan” methods for osteochondral regeneration. First, several examples of articular cartilage regeneration using AT-MSCs were introduced. Second, studies of osteochondral regeneration (not only cartilage but also subchondral bone) using AT-MSCs were described. Third, examples were presented wherein spheroids were produced using AT-MSCs for cartilage regeneration. Fourth, osteochondral regeneration following autologous implantation of AT-MSC scaffold-free 3D constructs, fabricated using the “mold” or “Kenzan” method, was considered. Finally, prospects of osteochondral regeneration by scaffold-free 3D constructs using AT-MSC spheroids were discussed.

scholarly journals Intra-articular injection of human umbilical cord mesenchymal stem cells ameliorates monosodium iodoacetate-induced osteoarthritis in rats by inhibiting cartilage degradation and inflammation

2021 ◽  
Vol 10 (3) ◽  
pp. 226-236
Author(s):  
Quan Zhang ◽  
E. Xiang ◽  
Wei Rao ◽  
Ya Qi Zhang ◽  
Cui Hong Xiao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Umbilical Cord ◽  
Cartilage Degradation ◽  
Human Umbilical Cord ◽  
Differentiation Potential ◽  
Tnf Α ◽  
Monosodium Iodoacetate ◽  
Safranin O

Aims This study aimed to investigate whether human umbilical cord mesenchymal stem cells (UC-MSCs) can prevent articular cartilage degradation and explore the underlying mechanisms in a rat osteoarthritis (OA) model induced by monosodium iodoacetate (MIA). Methods Human UC-MSCs were characterized by their phenotype and multilineage differentiation potential. Two weeks after MIA induction in rats, human UC-MSCs were intra-articularly injected once a week for three weeks. The therapeutic effect of human UC-MSCs was evaluated by haematoxylin and eosin, toluidine blue, Safranin-O/Fast green staining, and Mankin scores. Markers of joint cartilage injury and pro- and anti-inflammatory markers were detected by immunohistochemistry. Results Histopathological analysis showed that intra-articular injection of human UC-MSCs significantly inhibited the progression of OA, as demonstrated by reduced cartilage degradation, increased Safranin-O staining, and lower Mankin scores. Immunohistochemistry showed that human UC-MSC treatment down-regulated the expression of matrix metalloproteinase-13 (MMP13) and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), and enhanced the expression of type II collagen and ki67 in the articular cartilage. Furthermore, human UC-MSCs significantly decreased the expression of interleukin (IL)-1β and tumour necrosis factor-α (TNF-α), while increasing TNF-α-induced protein 6 and IL-1 receptor antagonist. Conclusion Our results demonstrated that human UC-MSCs ameliorate MIA-induced OA by preventing cartilage degradation, restoring the proliferation of chondrocytes, and inhibiting the inflammatory response, which implies that human UC-MSCs may be a promising strategy for the treatment of OA. Cite this article: Bone Joint Res 2021;10(3):226–236.

scholarly journals Joint Distraction Combined with Mesenchymal Stem Cell Intra-articular Injection Attenuates Osteoarthritis

2020 ◽  
Author(s):  
Yuanfeng Chen ◽  
Chuanwei Sun ◽  
Wenping Liu ◽  
Yuxin Sun ◽  
Sien Lin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Knee Joint ◽  
Subchondral Bone ◽  
Rat Model ◽  
Symptom Relief ◽  
External Fixators ◽  
Micro Ct ◽  
Joint Distraction

Abstract Background: Conservative treatments of osteoarthritis (OA) are limited to symptom relief and novel methods to attenuate OA progression are lacking.Objective: In this study, we investigated the effectiveness of knee joint distraction (KJD) combined with mesenchymal stem cells (MSCs) intra-articular injection (KJD+MSCs) in OA rat model.Methods: OA rat model was established by anterior cruciate ligament transection plus medial meniscus resection in right knee in SD rat. The KJD+MSCs treatment started 3 weeks after the OA surgery. There were two other groups as knee joint distraction only (KJD) and no treat (OA). Three weeks after the treatment, distraction external fixators were removed and rats were kept for further 3 weeks. The rats were then terminated, samples were subject to micro-CT and histology examinations to evaluate the changes of the articular cartilage tissues, subchondral bone and the secondary inflammation.Results: Safranin-O/fast green staining showed that articular cartilage injury was most obvious in the OA group than that in the KJD group and the least in the KJD+MSCs group. Immunohistochemistry examinations showed that the KJD+MSCs group had the lowest percentage of MMP13 or ColX positive chondrocytes comparing to other groups. Micro-CT data indicated that the abnormal change in the subchondral region of the tibia in the KJD+MSCs group was significantly less than that in the KJD group or OA group. Finally, immunohistochemistry result showed that the knee joint in the KJD+MSCs group had the least number of CD68-positive cells among all the groups.Conclusions: Joint distraction combined with mesenchymal stem cells injection alleviated cartilage degradation, reduced irregular ossification of subchondral bone and secondary inflammation, suggesting it could be a new method to halt the OA progression.

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.

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