Abstract:Mesenchymal stem cells (MSCs) can be effective in alleviating the progression of osteoarthritis (OA). However, low MSC retention and survival at the injection site frequently require high doses of cells and/or repeated injections, which are not economically viable and create additional risks of complications. In this study, we produced MSC-laden microcarriers in spinner flask culture as cell delivery vehicles. These microcarriers containing a low initial dose of MSCs administered through a single injection in … Show more
“…Along with this cell-based therapy, cell-free therapy using the secretome of MSCs is regarded as a promising therapeutic approach for OA [ 51 ]. Many researchers have co-cultured MSCs and chondrocyte cells in order to study the secretome of MSCs and their effect on OA [ 38 , 52 , 53 ]. They discovered that upon co-culturing with MSCs, the proliferation of chondrocyte cells increased, while the apoptosis decreased.…”
Co-culture system, in which two or more distinct cell types are cultured together, is advantageous in that it can mimic the environment of the in vivo niche of the cells. In this study, we presented a strategy to analyze the secretome of a specific cell type under the co-culture condition in serum-supplemented media. For the cell-specific secretome analysis, we expressed the mouse mutant methionyl-tRNA synthetase for the incorporation of the non-canonical amino acid, azidonorleucine into the newly synthesized proteins in cells of which the secretome is targeted. The azidonorleucine-tagged secretome could be enriched, based on click chemistry, and distinguished from any other contaminating proteins, either from the cell culture media or the other cells co-cultured with the cells of interest. In order to have more reliable true-positive identifications of cell-specific secretory bodies, we established criteria to exclude any identified human peptide matched to bovine proteins. As a result, we identified a maximum of 719 secreted proteins in the secretome analysis under this co-culture condition. Last, we applied this platform to profile the secretome of mesenchymal stem cells and predicted its therapeutic potential on osteoarthritis based on secretome analysis.
“…Along with this cell-based therapy, cell-free therapy using the secretome of MSCs is regarded as a promising therapeutic approach for OA [ 51 ]. Many researchers have co-cultured MSCs and chondrocyte cells in order to study the secretome of MSCs and their effect on OA [ 38 , 52 , 53 ]. They discovered that upon co-culturing with MSCs, the proliferation of chondrocyte cells increased, while the apoptosis decreased.…”
Co-culture system, in which two or more distinct cell types are cultured together, is advantageous in that it can mimic the environment of the in vivo niche of the cells. In this study, we presented a strategy to analyze the secretome of a specific cell type under the co-culture condition in serum-supplemented media. For the cell-specific secretome analysis, we expressed the mouse mutant methionyl-tRNA synthetase for the incorporation of the non-canonical amino acid, azidonorleucine into the newly synthesized proteins in cells of which the secretome is targeted. The azidonorleucine-tagged secretome could be enriched, based on click chemistry, and distinguished from any other contaminating proteins, either from the cell culture media or the other cells co-cultured with the cells of interest. In order to have more reliable true-positive identifications of cell-specific secretory bodies, we established criteria to exclude any identified human peptide matched to bovine proteins. As a result, we identified a maximum of 719 secreted proteins in the secretome analysis under this co-culture condition. Last, we applied this platform to profile the secretome of mesenchymal stem cells and predicted its therapeutic potential on osteoarthritis based on secretome analysis.
“…Some substances that are naturally present in the body may be valuable in preventing or treating osteoarthritis. Although most research is in its infancy, it is possible to use natural ingredients to heal injuries or speed up cartilage repair (18).…”
Section: The Effect Of Guava Fruit Hydroalcoholic Extract On Tnf-α Ge...mentioning
confidence: 99%
“…The high popularity of complementary and alternative drugs can be due to their advantages such as widespread availability, no side effects or low side effects, good effectiveness and low cost compared to synthetic drugs. Because osteoarthritis is an inflammatory disease associated with joint destruction, modulatory cytokines and nitric oxide produced by chondrocytes play a key role in disease progression (18).…”
Section: The Effect Of Guava Fruit Hydroalcoholic Extract On Tnf-α Ge...mentioning
Knee osteoarthritis is the most common joint disease and the most important cause of disability in elderly patients. Due to the side effects of nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of osteoarthritis, the use of herbs is recommended as an alternative treatment. The guava fruit can be considered as a natural medicine due to its antioxidant and anti-inflammatory properties. In this study, the effect of Psidium guajava hydroalcoholic extract was considered on reducing the expression of the resistin gene and TNF-α gene in articular chondrocytes of patients with knee osteoarthritis. For this purpose, cartilage chondrocytes of 10 Chinese patients with knee osteoarthritis, who were indicated for arthroplasty, were used for evaluating the effect of guava fruit on the expression of these genes. Articular chondrocytes were cultured under appropriate conditions and their viability was assessed by MTT assay. To increase the level of cytokines, cells were treated with lipopolysaccharide (LPS). They were kept in an incubator with 90% humidity at 37°C for the next steps. Then, the expression of the resistin gene and TNF-α gene was investigated by RNA isolation and cDNA preparation. The results showed that the expression of the resistin gene and TNF-α gene were reduced to 56.59% and 51.86%, respectively, by hydroalcoholic extract of guava fruit. Therefore, according to the results of this study and previous researches, the hydroalcoholic extract of guava fruit (Psidium guajava) can be considered as an effective complementary and alternative treatment for osteoarthritis of the knee.
“…Investigation of this in vivo observation showed that supernatants from co-culture of chondrocytes and MSCs in 3D constructs had fewer inflammatory factors than co-culture with MSCs in monolayers. An increased expression of genes related to chondrogenesis and ECM interactions were also observed, suggesting a high therapeutic potential of secretome when MSCs are cultured in 3D constructs [ 105 ]. Similarly, when MSC was encapsulated in alginate microbeads and co-cultured with patient-derived OA chondrocytes, paracrine factors induced a pro-regenerative microenvironment, increasing anabolic, proliferative, and anti-apoptotic processes [ 106 ].…”
Section: Application Of Secretomes For Cartilage Repairmentioning
Cartilage repair has been a challenge in the medical field for many years. Although treatments that alleviate pain and injury are available, none can effectively regenerate the cartilage. Currently, regenerative medicine and tissue engineering are among the developed strategies to treat cartilage injury. The use of stem cells, associated or not with scaffolds, has shown potential in cartilage regeneration. However, it is currently known that the effect of stem cells occurs mainly through the secretion of paracrine factors that act on local cells. In this review, we will address the use of the secretome—a set of bioactive factors (soluble factors and extracellular vesicles) secreted by the cells—of mesenchymal stem cells as a treatment for cartilage regeneration. We will also discuss methodologies for priming the secretome to enhance the chondroregenerative potential. In addition, considering the difficulty of delivering therapies to the injured cartilage site, we will address works that use hydrogels functionalized with growth factors and secretome components. We aim to show that secretome-functionalized hydrogels can be an exciting approach to cell-free cartilage repair therapy.
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