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      The human umbilical cord stem cells improve the viability of OA degenerated chondrocytes

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          Abstract

          Osteoarthritis (OA) affects a large number of patients; however, human umbilical cord stem cells exhibit therapeutic potential for treating OA. The aim of the present study was to explore the interaction between human umbilical cord stem cells and degenerated chondrocytes, and the therapeutic potential of human umbilical cord stem cells on degenerated chondrocytes. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were harvested from human umbilical cords, and flow cytometry was used to analyze the surface antigen markers, in addition, chondrogenic, osteogenic and adipogenic differentiation on the cells was investigated. OA cells at P3 were cocultured with hUC-MSCs in a separated co-culture system, and reverse transcription-polymerase chain reaction and western blot were used to evaluate the mRNA, and protein expression of collagen type II (Col2), SRY-box 9 (sox-9) and aggrecan. The level of inflammatory cytokines, tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-10, were analyzed by ELISA in the supernatant. hUC-MSCs grow in a fibroblastic shape with stable proliferation. hUC-MSCs expressed cluster of differentiation 44 (CD44), CD73, CD90, CD105; while did not express CD34, CD45, CD106, CD133. After multi-induction, hUC-MSCs were able to differatiate into adipogenic, osteogenic and chondrogenic lineage. hUC-MSCs inhibited the expression of matrix metalloproteinase-13, collagen type X α1 chain and cyclooxygenase-2 in OA chondrocytes, and enhanced the proliferation of OA chondrocytes, while OA chondrocytes stimulated the production of Col2, sox-9 and aggrecan and promoted hUC-MSCs differentiate into chondrocytes. Flow cytometry analysis demonstrated hUC-MSCs have a predominant expression of stem cell markers, while the hematopoietic and endothelial markers were absent. Osteogenic, chondrogenic and adipogenic differentiation was observed in certain induction conditions. hUC-MSCs improved the proliferation of OA chondrocytes and downregulated the expression of inflammatory cytokines, while OA chondrocytes promoted MSCs to differentiate into chondrocytes. Taken together, the co-culture of hUC-MSCs and OA chondrocytes may provide a therapeutic potential in OA treatment.

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          Most cited references39

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          Umbilical cord-derived mesenchymal stem cells: Their advantages and potential clinical utility.

          Human umbilical cord (UC) is a promising source of mesenchymal stem cells (MSCs). Apart from their prominent advantages, such as a painless collection procedure and faster self-renewal, UC-MSCs have shown the ability to differentiate into three germ layers, to accumulate in damaged tissue or inflamed regions, to promote tissue repair, and to modulate immune response. There are diverse protocols and culture methods for the isolation of MSCs from the various compartments of UC, such as Wharton's jelly, vein, arteries, UC lining and subamnion and perivascular regions. In this review, we give a brief introduction to various compartments of UC as a source of MSCs and emphasize the potential clinical utility of UC-MSCs for regenerative medicine and immunotherapy.
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            Protein synthesis and secretion in human mesenchymal cells derived from bone marrow, adipose tissue and Wharton’s jelly

            Introduction Different mesenchymal stromal cells (MSC) have been successfully isolated and expanded in vitro and nowadays they are tested in clinical trials for a wide variety of diseases. Whether all MSC express the same cell surface markers or have a similar secretion profile is still controversial, making it difficult to decide which stromal cell may be better for a particular application. Methods We isolated human mesenchymal stromal cells from bone marrow (BM), adipose tissue (AT) and Wharton’s jelly (WJ) and cultured them in fetal bovine serum supplemented media. We evaluated proliferation, in vitro differentiation (osteogenic, adipogenic and chondrogenic potential), expression of cell surface markers and protein secretion using Luminex and ELISA assays. Results Cell proliferation was higher for WJ-MSC, followed by AT-MSC. Differences in surface expression markers were observed only for CD54 and CD146. WJ-MSC secreted higher concentrations of chemokines, pro-inflammatory proteins and growth factors. AT-MSC showed a better pro-angiogenic profile and secreted higher amounts of extracellular matrix components and metalloproteinases. Conclusions Mesenchymal stromal cells purified from different tissues have different angiogenic, inflammatory and matrix remodeling potential properties. These abilities should be further characterized in order to choose the best protocols for their therapeutic use.
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              Role of Chondrocytes in Cartilage Formation, Progression of Osteoarthritis and Cartilage Regeneration

              Articular cartilage (AC) covers the diarthrodial joints and is responsible for the mechanical distribution of loads across the joints. The majority of its structure and function is controlled by chondrocytes that regulate Extracellular Matrix (ECM) turnover and maintain tissue homeostasis. Imbalance in their function leads to degenerative diseases like Osteoarthritis (OA). OA is characterized by cartilage degradation, osteophyte formation and stiffening of joints. Cartilage degeneration is a consequence of chondrocyte hypertrophy along with the expression of proteolytic enzymes. Matrix Metalloproteinases (MMPs) and A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTS) are an example of these enzymes that degrade the ECM. Signaling cascades involved in limb patterning and cartilage repair play a role in OA progression. However, the regulation of these remains to be elucidated. Further the role of stem cells and mature chondrocytes in OA progression is unclear. The progress in cell based therapies that utilize Mesenchymal Stem Cell (MSC) infusion for cartilage repair may lead to new therapeutics in the long term. However, many questions are unanswered such as the efficacy of MSCs usage in therapy. This review focuses on the role of chondrocytes in cartilage formation and the progression of OA. Moreover, it summarizes possible alternative therapeutic approaches using MSC infusion for cartilage restoration.
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                Author and article information

                Journal
                Mol Med Rep
                Mol Med Rep
                Molecular Medicine Reports
                D.A. Spandidos
                1791-2997
                1791-3004
                March 2018
                09 January 2018
                09 January 2018
                : 17
                : 3
                : 4474-4482
                Affiliations
                [1 ]Teaching Center of Experimental Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China
                [2 ]Department of Orthopedics, 455th Hospital of PLA, Shanghai 200052, P.R. China
                [3 ]School of Medicine, Dalian Medical University, Dalian, Liaoning 116044, P.R. China
                [4 ]Department of Plastic Surgery, 455th Hospital of PLA, Shanghai 200052, P.R. China
                Author notes
                Correspondence to: Professor Qingdong Shao, Department of Orthopedics, 455th Hospital of PLA, 338 West Huaihai Road, Shanghai 200052, P.R. China, E-mail: tianma1968×ingkong@ 123456126.com
                [*]

                Contributed equally

                Article
                mmr-17-03-4474
                10.3892/mmr.2018.8413
                5802223
                29328479
                87387a21-0ff2-494a-b984-5599e1854451
                Copyright: © Wang et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 11 July 2017
                : 05 December 2017
                Categories
                Articles

                human umbilical cord-derived mesenchymal stem cells,osteoarthritis,degenerated chondrocytes,differentiation,co-culture

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