Are Stem Cells Derived from Synovium and Fat Pad Able to Treat Induced Knee Osteoarthritis in Rats?

Zare, Reza; Tanideh, Nader; Nikahval, Behrooz; Mirtalebi, Maryam Sadat; Ahmadi, Nasrollah; Zarea, Shahrokh; Hosseinabadi, Omid Koohi; Bhimani, Rohan; Ashkani-Esfahani, Soheil

doi:10.1155/2020/9610261

Cited by 10 publications

(12 citation statements)

References 36 publications

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“…Four mg collagenase II (clostridium histolithicum; Sigma-Aldrich, St. Louis, MO, USA) dissolved in sterile PBS, and afterward was injected in the knee intra-articular space. After 3 days, injection was repeated [ 32 ].…”

Section: Methodsmentioning

confidence: 99%

“…Three months after onset of treatment, rats were killed in a CO 2 chamber, and thereupon radiography was taken from the lateral aspect of knee joint using radiographic equipment (AxiomMultix M Radiographic Unit, SiemensTM, Germany). Osteoarthritis in terms of presence of osteophytes, joint space narrowing, and subchondral sclerosis as Radiological grading system was assessed by a blinded radiologist [ 32 , 33 ].…”

Section: Methodsmentioning

confidence: 99%

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Attenuation of osteoarthritis progression through intra-articular injection of a combination of synovial membrane-derived MSCs (SMMSCs), platelet-rich plasma (PRP) and conditioned medium (secretome)

et al. 2022

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Purpose Osteoarthritis (OA) as a progressive destructive disease of articular cartilage is the most common joint disease characterized by reduction of joint cartilage thickness, demolition of cartilage surface and new bone formation. To overcome these problems, the purpose of the current research was to evaluate and compare the in vivo effects of synovial membrane-derived mesenchymal stem cell (SMMSCs), platelet-rich plasma (PRP) and conditioned medium (secretome) on collagenase II-induced rat knee osteoarthritis (KOA) remedy. Methods For the first step, SMMSCs were isolated and characterized. Also, secretome was collected from SMMSCs culture. Furthermore, PRP was collect from the rat heart venous blood. Second, two injection of collagenase II with an interval of 3 days was performed in the knee intra-articular space to induce osteoarthritis. Two weeks later, animals were randomly divided into 6 groups. Control group without treatment, positive group: taken an intra-articular sodium hyaluronate injection (0.1 ml), treatment groups taken an intra-articular injection of; treatment 1: SMMSCs (5 × 106), treatment 2: SMMSCs (5 × 106)/secretome (50 µl), treatment 3: SMMSCs (5 × 106)/PRP (50 µl), and treatment 4: SMMSCs (5 × 106)/ secretome (50 µl)/ PRP (50 µl). Three months later, rats were killed and the following assessments were executed: radiography, histopathology, and immunohistochemistry. Results Our findings represented that a combination of the SMMSCs/secretome/PRP had a considerable effect on glycosaminoglycans (GAGs) and collagen II contents, articular cartilage preservation, compared with other groups. In addition, combination of the SMMSCs with PRP and secretome showed the lowest expression of mmp3, while SOX9 had the highest expression in comparison with other groups. Also, SMMSCs-injected groups demonstrated better results compared with positive and control groups. Conclusions Injecting a combination of the SMMSCs/secretome/PRP resulted in better efficacy in terms of joint space width, articular cartilage surface continuity and integrity, sub-chondral bone and ECM constituents such as collagen II. Indeed, transplantation of this combination could be considered as a preliminary therapy for clinical trial study in the future.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Attenuation of osteoarthritis progression through intra-articular injection of a combination of synovial membrane-derived MSCs (SMMSCs), platelet-rich plasma (PRP) and conditioned medium (secretome)

et al. 2022

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“…Synovium-derived mesenchymal stem cells (S-MSCs) have attracted considerable attention due to their high chondrogenic potential, and are recognized as a viable option to repair cartilage [ 124 , 125 ]. Zare et al conducted a research study on rats wherein animals treated with S-MSCs showed significantly better results in every pathological evaluated criterion compared to control, HA and ADSCs groups [ 126 ]. Furthermore, another research study reported the efficacy of S-MSCs in OA treatment, showing a significant reduction in serum inflammatory factors and cartilage protection thanks to the upregulation of chondrogenic gene expression in meniscus chondrocytes [ 127 ].…”

Section: Bioregenerative Therapies In Osteoarthritismentioning

confidence: 99%

Cell and Cell Free Therapies in Osteoarthritis

et al. 2021

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Osteoarthritis (OA) is the most common articular disease in adults and has a current prevalence of 12% in the population over 65 years old. This chronic disease causes damage to articular cartilage and synovial joints, causing pain and leading to a negative impact on patients’ function, decreasing quality of life. There are many limitations regarding OA conventional therapies—pharmacological therapy can cause gastrointestinal, renal, and cardiac adverse effects, and some of them could even be a threat to life. On the other hand, surgical options, such as microfracture, have been used for the last 20 years, but hyaline cartilage has a limited regeneration capacity. In recent years, the interest in new therapies, such as cell-based and cell-free therapies, has been considerably increasing. The purpose of this review is to describe and compare bioregenerative therapies’ efficacy for OA, with particular emphasis on the use of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP). In OA, these therapies might be an alternative and less invasive treatment than surgery, and a more effective option than conventional therapies.

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“…During the past decades, the existence of highly regenerative mesenchymal stem cells was et al 2020; Zare et al 2020) . Furthermore, the MSC numbers obtained from adipose tissue are much higher than from the bone marrow (Wolfstadt et al 2015).…”

Section: Articular Cartilage Degradationmentioning

confidence: 99%

“…Especially ASCs are of great interest, which have been shown to prevent OA development in rats (Zare et al 2020) and to reduce pain and regenerate cartilage in OA patients after intraarticular injection (Freitag et al 2020). In order to repair the damaged cartilage, the highly proliferative sASCs with greater chondrogenic capacity in producing ECM molecules would be advantageous compared with the limited proliferative and chondrogenic function of mature chondrocytes (McGonagle, Baboolal, and Jones 2017).…”

Section: Ne Influences the Regenerative Potential Of Sascsmentioning

confidence: 99%

Sympathetic influences on articular cartilage regeneration capacity and osteoarthritis manifestation

Bagdadi¹

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The pathogenesis of osteoarthritis (OA) involves articular cartilage, synovial tissue and subchondral bone and is therefore a disease of the whole joint. OA is characterized by progressive degradation of cartilage, synovial inflammation, osteophyte formation and subchondral bone sclerosis. Cartilage-surrounding tissues are innervated by tyrosine hydroxylase (TH)-positive sympathetic nerve fibers with the most important sympathetic neurotransmitter norepinephrine (NE) detected in the synovial fluid of OA patients. Furthermore, adrenergic receptors are expressed in different knee joint tissues. Most in vitro studies indicate a potential role of the β2-adrenergic receptor, which has been not investigated during OA pathogenesis in vivo. The role of the sympathetic nervous system (SNS) in OA progression has not yet been studied. Therefore, the objective of this study was to analyze how the SNS and NE influence the MSC dependent cartilage regeneration in vitro and the OA pathogenesis and manifestation in vivo. In the first part of this study, the effect of NE on the chondrogenesis of sASC, which are known to play an important role in cartilage regeneration was analyzed in vitro. In the second part of this study, the role of the SNS was studied in vivo in mice that were sympathectomized chemically followed by surgically induced OA. The specific focus was on the β2-adrenergic receptor effects on OA pathogenesis, which were analyzed in β2-adrenergic receptor-deficient mice. The in vitro experiments have shown that NE reduced the chondrogenic potential of sASCs by decreasing the expression of type II collagen and sGAG. NE mediated these effects mainly by the α2-AR signalling. Furthermore, NE treatment led to activation of the ERK1/2 signal pathway. These findings suggested that the sympathetic neurotransmitter NE might suppress the chondrogenic capacity of MSC and their dependent cartilage regeneration and may also play a role in OA progression and manifestation. The in vivo study has shown that sympathectomy reduced synovial TH-positive nerve fibers in the synovium and the NE concentration in the spleen significantly. In WT mice, DMM leads to increased NE concentrations in the spleen compared to sham mice indicating an increased SNS activity after mechanical stress or inflammation due to DMM. Sympathectomy leads to less pronounced cartilage degeneration (OARSI score) after DMM compared to DMM in WT mice. Furthermore, the release of the type II collagen degradation fragment CTX-II was abolished in Syx DMM mice compared to WT DMM mice, suggesting that less SNS activity due to sympathectomy reduced the cartilage degeneration during OA pathogenesis. Similarly, sympathectomy decreased the synovitis score significantly after DMM compared to DMM in WT mice. Synovitis in WT mice was accompanied by increased MMP-13 expression in the synovium after DMM, compared to Syx mice. Cartilage degeneration seemed to be driven mainly by the increased synovial inflammation accompanied by an increased MMP13 expression in synoviocytes and not in chondrocytes. The pathological changes in synovium and cartilage might also be linked to each other, as indicated by the moderate correlation between the synovial inflammation (synovitis score) and cartilage degeneration (OARSI score). Subchondral bone volume as well the thickness of the subchondral bone plate (SCBP) and calcified cartilage (CC) were increased in Syx mice compared to WT after DMM. The data on DMM induction in β2-AR deficient mice revealed that the β2-AR signaling is involved in cartilage degeneration and the aggravated subchondral bone changes as these mice had less pronounced cartilage degeneration compared to WT mice. While the cartilage degeneration was similar, the subchondral bone changes were more pronounced in β2-AR deficient mice compared to the Syx mice. Overall, the SNS had differential effects in cartilage, synovium and subchondral bone. A reduced SNS activity by sympathectomy attenuated cartilage degeneration and synovitis but aggravated the OA specific subchondral bone changes. These findings provide new insights into the development of novel therapeutic strategies for OA by targeting the SNS in a tissue- specific manner.

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Are Stem Cells Derived from Synovium and Fat Pad Able to Treat Induced Knee Osteoarthritis in Rats?

Cited by 10 publications

References 36 publications

Attenuation of osteoarthritis progression through intra-articular injection of a combination of synovial membrane-derived MSCs (SMMSCs), platelet-rich plasma (PRP) and conditioned medium (secretome)

Attenuation of osteoarthritis progression through intra-articular injection of a combination of synovial membrane-derived MSCs (SMMSCs), platelet-rich plasma (PRP) and conditioned medium (secretome)

Cell and Cell Free Therapies in Osteoarthritis

Sympathetic influences on articular cartilage regeneration capacity and osteoarthritis manifestation

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