Multipotent mesenchymal stem cells from adult human synovial membrane (original) (raw)
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Mesenchymal stem cells in arthritic diseases
Arthritis Research & Therapy, 2008
Mesenchymal stem cells (MSCs), the nonhematopoietic progenitor cells found in various adult tissues, are characterized by their ease of isolation and their rapid growth in vitro while maintaining their differentiation potential, allowing for extensive culture expansion to obtain large quantities suitable for therapeutic use. These properties make MSCs an ideal candidate cell type as building blocks for tissue engineering efforts to regenerate replacement tissues and repair damaged structures as encountered in various arthritic conditions. Osteoarthritis (OA) is the most common arthritic condition and, like rheumatoid arthritis (RA), presents an inflammatory environment with immunological involvement and this has been an enduring obstacle that can potentially limit the use of cartilage tissue engineering. Recent advances in our understanding of the functions of MSCs have shown that MSCs also possess potent immunosuppression and anti-inflammation effects. In addition, through secretion of various soluble factors, MSCs can influence the local tissue environment and exert protective effects with an end result of effectively stimulating regeneration in situ. This function of MSCs can be exploited for their therapeutic application in degenerative joint diseases such as RA and OA. This review surveys the advances made in the past decade which have led to our current understanding of stem cell biology as relevant to diseases of the joint. The potential involvement of MSCs in the pathophysiology of degenerative joint diseases will also be discussed. Specifically, we will explore the potential of MSC-based cell therapy of OA and RA by means of functional replacement of damaged cartilage via tissue engineering as well as their antiinflammatory and immunosuppressive activities. 1. Biology of mesenchymal stem cells Characteristics and tissue distribution Originally derived from bone marrow [1,2], MSCs and MSClike cells have been identified to exist in and can be isolated from a large number of adult tissues, where they are postulated to carry out the function of replacing and regenerating local cells that are lost to normal tissue turnover, injury, or aging. These tissues include adipose, periosteum, synovial membrane, synovial fluid (SF), muscle, dermis, deciduous
Marrow-Derived and Synovium-Derived Mesenchymal Stem Cells
2006
Previous studies have reported that mesenchymal stem cells (MSC) may be isolated from the synovial membrane by the same protocol as that used for synovial fibroblast cultivation, suggesting that MSC correspond to a subset of the adherent cell population, as MSC from the stromal compartment of the bone marrow (BM). The aims of the present study were, first, to better characterize the MSC derived from the synovial membrane and, second, to compare systematically, in parallel, the MSC-containing cell populations isolated from BM and those derived from the synovium, using quantitative assays. Fluorescent-activated cell sorting analysis revealed that both populations were negative for CD14, CD34 and CD45 expression and that both displayed equal levels of CD44, CD73, CD90 and CD105, a phenotype currently known to be characteristic of BM-MSC. Comparable with BM-MSC, such MSC-like cells isolated from the synovial membrane were shown for the first time to suppress the T-cell response in a mixed lymphocyte reaction, and to express the enzyme indoleamine 2,3-dioxygenase activity to the same extent as BM-MSC, which is a possible mediator of this suppressive activity. Using quantitative RT-PCR these data show that MSC-like cells from the synovium and BM may be induced to chondrogenic differentiation and, to a lesser extent, to osteogenic differentiation, but the osteogenic capacities of the synoviumderived MSC were significantly reduced based on the expression of the markers tested (collagen type II and aggrecan or alkaline phosphatase and osteocalcin, respectively). Transcription profiles, determined with the Atlas Human Cytokine/Receptor Array, revealed discrimination between the MSC-like cells from the synovial membrane and the BM-MSC by 46 of 268 genes. In particular, activin A was shown to be one major upregulated factor, highly secreted by BM-MSC. Whether this reflects a different cellular phenotype, a different amount of MSC in the synovium-derived population compared with BM-MSC adherent cell populations or the impact of a different microenvironment remains to be determined. In conclusion, although the BM-derived and synovium-derived MSC shared similar phenotypic and functional properties, both their differentiation capacities and transcriptional profiles permit one to discriminate the cell populations according to their tissue origin.
Arthritis and Rheumatism, 2008
ObjectiveArthritic synovial fluid (SF) contains mesenchymal stem cells (MSCs), which could simply reflect their shedding from diseased joint structures. This study used the bovine model to explore SF MSCs in health and enumerated them at the earliest stages of human osteoarthritis (OA) in radiographically normal joints.Arthritic synovial fluid (SF) contains mesenchymal stem cells (MSCs), which could simply reflect their shedding from diseased joint structures. This study used the bovine model to explore SF MSCs in health and enumerated them at the earliest stages of human osteoarthritis (OA) in radiographically normal joints.MethodsClonogenicity and multipotentiality of normal bovine SF MSCs were compared with donor-matched bone marrow (BM) MSCs at the single-cell level. The colony-forming unit–fibroblastic assay was used for MSC enumeration. The XTT assay was employed to assess cell proliferation, and flow cytometry was used to investigate the marker phenotype of bovine and human SF MSCs.Clonogenicity and multipotentiality of normal bovine SF MSCs were compared with donor-matched bone marrow (BM) MSCs at the single-cell level. The colony-forming unit–fibroblastic assay was used for MSC enumeration. The XTT assay was employed to assess cell proliferation, and flow cytometry was used to investigate the marker phenotype of bovine and human SF MSCs.ResultsSingle MSCs were present in normal bovine SF, and 96% of them were able to expand at least 1 million–fold. These cells were CD271–, multipotential, considerably more clonogenic, and less adipogenic than matched BM MSCs. In both pellet assays and on polyglycolic acid scaffolds, SF clones displayed consistent chondrogenic differentiation, while BM clones were variable. MSCs were present in arthroscopically normal human joints and were increased 7-fold in early OA (P = 0.034). Their numbers correlated with numbers of free microscopic synovial tissue fragments (r = 0.826, P < 0.0001). OA SF had a growth-promoting effect on synovial MSCs.Single MSCs were present in normal bovine SF, and 96% of them were able to expand at least 1 million–fold. These cells were CD271–, multipotential, considerably more clonogenic, and less adipogenic than matched BM MSCs. In both pellet assays and on polyglycolic acid scaffolds, SF clones displayed consistent chondrogenic differentiation, while BM clones were variable. MSCs were present in arthroscopically normal human joints and were increased 7-fold in early OA (P = 0.034). Their numbers correlated with numbers of free microscopic synovial tissue fragments (r = 0.826, P < 0.0001). OA SF had a growth-promoting effect on synovial MSCs.ConclusionThis study confirms the presence of MSCs in normal SF and shows their numerical increase in early human OA. SF MSCs are likely to originate from synovium. These findings provide a platform for the exploration of the potential role of SF MSCs in joint homeostasis and for investigation of their utility in novel joint regeneration strategies.This study confirms the presence of MSCs in normal SF and shows their numerical increase in early human OA. SF MSCs are likely to originate from synovium. These findings provide a platform for the exploration of the potential role of SF MSCs in joint homeostasis and for investigation of their utility in novel joint regeneration strategies.
Molecular and Cellular Biomedical Sciences
Background: Mesenchymal stem cells (MSCs) are the cells which has high renewal capacity and and are capable for differentiating into some types of cells. MSCs can be obtained from several tissues including bone marrow, synovial membrane, blood, adipose tissue and periosteum. The proliferation and self-repair ability of MSCs are the advantages to use as stem cells-based therapy of various diseases. The aim of this study was to determine the differentiation, characterization and priliferation of synovial membrane-derived MSCs (SM-MSCs).Materials and Methods: The cells proliferation capacity was determined by cell counting using trypan blue, characterization of MSCs (cluster of differentiation (CD)90, CD11b, CD73, CD34, CD19, CD45, CD105 and human leukocyte antigen-DR isotype (HLA-DR)) using flow cytometry analysis, and differentiation capability into three lineage cells was determined with red alcian blue, oil red O and alizarin staining.Results: The type culture of SM-MSCs was adhere...
Stem Cell Reviews and Reports, 2018
The musculoskeletal system includes tissues that have remarkable regenerative capabilities. Bone and muscle sustain microdamage throughout the lifetime, yet they continue to provide the body with the support that is needed for everyday activities. Our current understanding is that the regenerative capacity of the musculoskeletal system can be attributed to the mesenchymal stem/ stromal cells (MSCs) that reside within its different anatomical compartments. These MSCs can replenish various tissues with progenitor cells to form functional cells, such as osteoblasts, chondrocytes, myocytes, and others. However, with aging and in certain disorders of the musculoskeletal system such as osteoarthritis or osteoporosis, this regenerative capacity of MSCs appears to be lost or diverted for the production of other non-functional cell types, such as adipocytes and fibroblasts. In this review, we shed light on the tissue sources and subpopulations of MSCs in the musculoskeletal system that have been identified in animal models, discuss the mechanisms of their anti-inflammatory action as a prerequisite for their tissue regeneration and their current applications in regenerative medicine. While providing up-to-date evidence of the role of MSCs in different musculoskeletal pathologies, in particular in osteoporosis and osteoarthritis, we share some thoughts on their potential as diagnostic markers in musculoskeletal health and disease.
Isolation and characterization of synovial mesenchymal stem cells
Folia biologica, 2011
Synovial membrane and synovial fluid represent a good source of mesenchymal stem cells. They have been regarded as a promising therapeutic tool for musculoskeletal regeneration. Synovium-derived mesenchymal stem cells have higher expression of CD44 and better chondrogenic potential in vitro than mesenchymal stem cells from other tissues. In this study we compared mesenchymal stem cells from synovium and synovial fluid on the base of morphological, immunophenotype and differentiation features. A heterogeneous population of cells with different morphology was obtained after isolation and 4-day cultivation. The mesenchymal stem cell immunophenotype was confirmed by positive expression of CD105, CD90, and CD44 by flow cytometry and cells were negative for CD45. CD105+ cells were selected by immunomagnetic separation after 2-4 weeks of cultivation. The percentage of CD105+ cells in the mesenchymal stem cell population from synovia was between 40-50 % before immunomagnetic separation and ...
Journal of cellular physiology, 2018
Mesenchymal stromal cells (MSC) isolated from synovial tissues constitute a novel source of stem-like cells with promising applications in cartilage regeneration and potentially in other regenerative medicine and tissue-engineering settings. Detailed characterization of these cells is lacking, thus compromising their full potential. Here we present the detailed characterization of the ex vivo expansion of synovium-derived stromal cells collected by three different biopsy methods: synovium-direct biopsy, arthroscopic trocar shaver blade filtrate, and cells isolated from synovial fluid (SF) samples. Isolation success rates were >75% for all sources. MSC obtained from the different samples displayed the characteristic immunophenotype of adult MSC, expressing CD73, CD90, and CD105. Arthroscopic shaver blade-derived cells showed the higher proliferation capacity measured by the fold increase (FI) in total cell number over several passages and considering their cumulative population do...