Human mesenchymal stem cells in synovial fluid increase in the knee with degenerated cartilage and osteoarthritis

Sekiya, Ichiro; Ojima, Miyoko; Suzuki, S.; Yamaga, Mika; Horie, Masafumi; Koga, Hideyuki; Tsuji, Kunikazu; Miyaguchi, Ken; Ogishima, Soichi; Tanaka, Hiroshi; Muneta, Takeshi

doi:10.1002/jor.22029

Cited by 188 publications

(200 citation statements)

References 34 publications

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“…Surprisingly, donor age had no signficiant effect on initial CFU concentrations or cell proliferation. The cell populations expanded in monolayer culture expressed osteogenic, adipogenic and chondrogenic phenotypes under standard in vitro culture conditions, consistent with findings in similar studies [4,5,10,12], and reflecting the multi-lineage potential requirement for MSCs.…”

Section: Discussionsupporting

confidence: 87%

“…The presence of MSCs in synovial fluids was first reported in 2004 [8], and subsequent studies have corroborated this finding in several model species, including the horse [9][10][11][12]. The proliferative and differentiation capacities of synovial fluidderived progenitor cells have varied between studies [9][10][11][12][13], but in all cases, these cells were capable of chondrogenesis.…”

Section: Introductionmentioning

confidence: 82%

“…The proliferative and differentiation capacities of synovial fluidderived progenitor cells have varied between studies [9][10][11][12][13], but in all cases, these cells were capable of chondrogenesis. However, the specific chondrogenic lineage of synovial fluidderived chondroprogenitors (SF-CP) has not been defined.…”

Section: Introductionmentioning

confidence: 99%

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Phenotypic characterization of equine synovial fluid-derived chondroprogenitor cells

Chen¹,

Bianchessi²,

Pondenis³

et al. 2016

Stem Cell Biol Res

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Background: Progenitor cells exist in most tissues and body fluids. Synovial fluid chondroprogenitor cells have been described in several species; however, the specific phenotypic characteristics of these cells have not been defined. This study addressed the impacts of joint location and donor age variation on synovial fluid chondroprogenitor numbers, and determined whether synovial fluid chondroprogenitors express hypertrophic characteristics or a non-endochondral phenotype in chondrogenic culture. Methods: Synovial fluid was aspirated from the joints of healthy adult horses, and cells in the aspirates were expanded through two monolayer passages. The number of colony-forming units (CFU) in each aspirate was assessed after 14 days. Population doublings (PD) and PD times were calculated during the subsequent two passages. Passage 3 cells were used to determine osteogenic and adipogenic capacities, or were transferred to pellet cultures in chondrogenic medium containing TGF-β1 or BMP-2. Bone marrowderived MSCs and primary articular chondrocytes were cultured under similar conditions to provide reference values for chondrogenesis. Chondrogenesis was assessed by measuring collagen type II protein and sulfated glycosaminoglycan secretion, expression of chondrogenic mRNAs, and induction of ALP activity. Results: CFU counts varied considerably, but the majority of aspirates contained <50 CFU/ml. PDs were consistently between 2.0 and 3.0 during both passages. PD times varied from 0.2-0.4 days. Proliferation was not significantly influenced by anatomical location or donor age. Equine synovial fluid progenitors expressed osteogenic, adipogenic and chondrogenic phenotypes under appropriate conditions. Under chondrogenic conditions, synovial fluid cells increased collagen and aggrecan mRNA expression to levels comparable to bone marrow MSCs, although collagen type II protein secretion was less than half that of articular chondrocytes. In contrast to bone marrow MSCs, synovial fluid chondroprogenitors did not express collagen type X or increase ALP activity in response to TGF-β1 or BMP-2. Consistent with these observations, Runx2 and Mef2C expression in synovial fluid chondroprogenitors was 20-40 fold lower than in bone marrow MSCs. Conclusions: Synovial fluid chondroprogenitors are capable of robust non-hypertrophic chondrogenesis, whether stimulated by TGF-β1 or by BMP-2. These results indicate that synovial fluid cells are phenotypically suitable for articular cartilage repair/regeneration, although strategies to accelerate cell proliferation and synthesize a functional cartilage matrix in vivo will be required for clinically feasible cellbased therapies.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 82%

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Phenotypic characterization of equine synovial fluid-derived chondroprogenitor cells

Chen¹,

Bianchessi²,

Pondenis³

et al. 2016

Stem Cell Biol Res

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“…4 In OA, our lab and others have shown that sfMPCs have increased proliferative but reduced chondrogenic capacities. 5,6 OA is a multifaceted disease and many factors may contribute to the change in phenotype between normal and OA sfMPCs. The synovial environment changes physically, chemically, and physiologically with injury or the onset of disease.…”

Section: Introductionmentioning

confidence: 99%

Ion channel expression and function in normal and osteoarthritic human synovial fluid progenitor cells

et al. 2016

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Osteoarthritis (OA) is a chronic disease affecting the cartilage of over 15% of Canadians. Synovial fluid mesenchymal progenitor cells (sfMPCs) are present in joints and are thought to contribute to healing. OA sfMPCs have a greater proliferative ability but decreased chondrogenic potential. However, little is known about the factors influencing/regulating the differences between normal and OA sfMPCs. Recently, our lab has shown that sfMPC chondrogenic differentiation in vitro is favorably biased toward a similar osmotic environment as they experience in vivo. The current study now examines the expression and functionality of a variety of ion channels in sfMPCs derived from normal individuals and early OA patients. Results indicated that there is differential ion channel regulation at the functional level and expression level in early OA sfMPCs. All ion channels were upregulated in early OA compared to normal sfMPCs with the exception of KCNMA1 at the mRNA level. At the protein level, TRPV4 was over expressed in early OA sfMPCs, while KCNJ12 and KCNMA1 were unchanged between normal and early OA sfMPCs. At the functional level, the inward rectifying potassium channel was under expressed in early OA sfMPCs, however the membrane potential was unchanged between normal and early OA sfMPCs. In the synovial environment itself, a number of differences in ion concentration between normal and early OA synovial fluid were observed. These findings suggest that normal and OA progenitor cells demonstrate functional differences in how they interact with the synovial ion environment.

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“…Trabecular bone MSCs sorted on the basis of CD271 expression revealed that OA MSCs exhibit an age-related proliferation deficiency in vitro [69]. In OA patients, the number of MSCs in the synovial fluid compartment is much greater than in samples from healthy joints, and the number of cells increased with the severity of OA progression [70]. Synovial fluid MSCs show greater chondrogenic capability than MSCs separated from bone marrow [71].…”

Section: Atypical Activity Of Mscs In Oamentioning

confidence: 99%

Treatment of osteoarthritis with mesenchymal stem cells

Wang

Cao

2014

Sci. China Life Sci.

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Osteoarthritis (OA) is one of the most prevalent joint diseases with prominent symptoms affecting the daily life of millions of middle aged and elderly people. Despite this, there are no successful medical interventions that can prevent the progressive destruction of OA joints. The onset of pathological changes in OA is associated with deviant activity of mesenchymal stem cells (MSCs), the multipotent precursors of connective tissue cells that reside in joints. Current therapies for OA have resulted in poor clinical outcomes without repairing the damaged cartilage. Intra-articular delivery of culture-expanded MSCs has opened new avenues of OA treatment. Pre-clinical and clinical trials demonstrated the feasibility, safety, and efficacy of MSC therapy. The Wnt/β-catenin, bone morphogenetic protein 2, Indian hedgehog, and Mitogen-activated protein kinase signaling pathways have been demonstrated to be involved in OA and the mechanism of action of MSC therapies. osteoarthritis, mesenchymal stem cells, intra-articular delivery Citation:Wang W, Cao W. Treatment of osteoarthritis with mesenchymal stem cells.

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Human mesenchymal stem cells in synovial fluid increase in the knee with degenerated cartilage and osteoarthritis

Cited by 188 publications

References 34 publications

Phenotypic characterization of equine synovial fluid-derived chondroprogenitor cells

Phenotypic characterization of equine synovial fluid-derived chondroprogenitor cells

Ion channel expression and function in normal and osteoarthritic human synovial fluid progenitor cells

Treatment of osteoarthritis with mesenchymal stem cells

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