Repetitive allogeneic intraarticular injections of synovial mesenchymal stem cells promote meniscus regeneration in a porcine massive meniscus defect model

Hatsushika, Daisuke; Muneta, Takeshi; Nakamura, Tomomasa; Horie, Masafumi; Koga, Hideyuki; Nakagawa, Yusuke; Tsuji, Kunikazu; Hishikawa, Shuji; Kobayashi, Eiji; Sekiya, Ichiro

doi:10.1016/j.joca.2014.04.028

Cited by 141 publications

(104 citation statements)

References 29 publications

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“…Several studies have demonstrated the therapeutic capacity of SMSCs. Compared with their respective controls, the quantity and quality of regenerated tissue were found significantly greater in those groups treated with SMSCs (Matsukura et al 2014;Hatsushika et al 2014).…”

Section: Discussionmentioning

confidence: 75%

A study to identify and characterize the stem/progenitor cell in rabbit meniscus

et al. 2016

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The repair of meniscus in the avascular zone remains a great challenge, largely owing to their limited healing capacity. Stem cells based tissue engineering provides a promising treatment option for damaged meniscus because of their multiple differentiation potential. We hypothesized that meniscusderived stromal cells (MMSCs) may be present in meniscal tissue, and if their pluripotency and character can be established, they may play a role in meniscal healing. To test our hypothesis, we isolated MMSCs, bone marrow-derived stromal cells (BMSCs) and fibrochondrocytes from rabbits. In order to avoid bone marrow mesenchymal stromal cell contamination, the parameniscal tissues and vascular zone of meniscus were removed. The characters of these three types of cells were identified by evaluating morphology, colony formation, proliferation, immunocytochemistry and multi-differentiation. Moreover, a wound in the center of rabbit meniscus was created and used to analyze the effect of BMSCs and MMSCs on wounded meniscus healing. BMSCs & MMSCs expressed the stem cell markers SSEA-4, Nanog, nucleostemin and STRO-1, while fibrochondrocytes expressed none of these markers. Morphologically, MMSCs displayed smaller cell bodies and larger nuclei than ordinary fibrochondrocytes. Moreover, it was certified that MMSCs and BMSCs were all able to differentiate into adipocytes, osteocytes, and chondrocytes in vitro. However, more cartilage formation was found in wounded meniscus filled with MMSCs than that filled with BMSCs. We showed that rabbit menisci harbor the unique cell population MMSCs that has universal stem cell characteristics and posses a tendency to differentiate into chondrocytes. Future research should investigate the mechanobiology of MMSCs and explore the possibility of using MMSCs to more effectively repair or regenerate injured meniscus.

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Section: Discussionmentioning

confidence: 75%

A study to identify and characterize the stem/progenitor cell in rabbit meniscus

et al. 2016

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“…For in vitro osteogenic differentiation expanded SF cells were seeded in triplicate at a density of 1x10 4 cells/cm 2 in 8-well plates (BD Falcon Culture Slides) in the complete and Stem PRO osteogenesis medium for 21 days. Some cultures were interrupted the fi fth day to determine alkaline phosphatase (AP) activity using Alkaline Phosphatase Detection Kit (Sigma) according to manufacturer's instructions.…”

Section: In Vitro Differentiation Of the Sf Cellsmentioning

confidence: 99%

“…Neither of these treatments leads to cartilage regeneration nor permanent improvement of the initial damage. As described previously, some of SF cells also have mesenchymal stem cell (MSC) like properties and important regenerative potential [2][3][4][5][6]. Dogs are the model recommended by the Osteoarthritis Research Society International (OARSI) for investigation of OA pathogenesis [15].…”

Section: Introductionmentioning

confidence: 99%

“…On the contratry, mechanism of steady state mobilization of synovial membrane (SM) synoviocytes into the SF has not been investigated. Also, the function of synoviocytes in the SF is just beginning to be defi ned and the fi rst data obtained in rabbits [2,3] and some very recent experimental data in porcine, rats and rabbits point that SF cells could directly differentiate into chondrocytes and meniscal cells when hyaline cartilage or meniscal injury is provoked [2][3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

“…In several animal species and humans, multipotency and a large proliferative potential i.e. mesenchymal stem cell-like properties of SM and SF synoviocytes have been described [2][3][4][5][6][8][9][10][11]. Moreover, chondrogenic potential of in vitro expanded SF synoviocytes has been proved to be more consistent than the same potential of bone marrow MSCs [12].…”

Section: Introductionmentioning

confidence: 99%

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Proliferation And Differentiation Potential Of Canine Synovial Fluid Cells

et al. 2015

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The aim of this study was to determine whether synovial fl uid (SF) of dogs contains cells that have characteristics of MSCs and to describe their differentiation potential. SF adherent cells from 5 young German shepherd dogs (average 3.8 ± 0.9 years) were expanded (37ºC, 5% CO 2 , humidifi ed atmosphere) three weeks before their phenotype was characterized by fl ow-cytometry for the presence of CD90 and CD34. Population doubling time (PDT), number of CFU-F and adipogenic, osteogenic and chondrogenic potentials have been determined in vitro. In early passages PTD was 31 ± 10 hours and expansion fold after 3 sub cultivations (9 days) theoretically could be 372 ± 134. At P1, 0.55 ± 0.05% of SF cells had the ability to form CFU-F. Sixty-six percent of cells expressed CD90 and none of the cells expressed markers of hematopoietic cells. Oil Red O staining has shown accumulation of fat droplets in cells grown in adipogenic medium, while deposits of calcium in the osteogenic medium were evidenced with Alizarin red staining. SF cultured in hondrogenic and control medium in three-dimensional conditions formed a cartilage-like tissue. Alcian blue staining of pellets' slides have shown a signifi cant amount of glycosaminoglycans (GAGs) and immunohistochemistry analysis documented collagen type II expression. The amount of GAGs in pellets grown in both conditions showed no difference. SF cells in vitro exhibited osteogenic, adipogenic and chondrogenic differentiation potentials, suggesting the presence of different mesenchymal progenitors. These results also demonstrated that SF cells have a spontaneous chondrogenic potential that should be further explored for possible tissue engineering protocols.

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Current Concepts in Meniscus Tissue Engineering and Repair

Bilgen

Jayasuriya

Owens

2018

Adv Healthcare Materials

108

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The meniscus is the most commonly injured structure in the human knee. Meniscus deficiency has been shown to lead to advanced osteoarthritis (OA) due to abnormal mechanical forces, and replacement strategies for this structure have lagged behind other tissue engineering endeavors. The challenges include the complex 3D structure with individualized size parameters, the significant compressive, tensile and shear loads encountered, and the poor blood supply. In this progress report, a review of the current clinical treatments for different types of meniscal injury is provided. The state-of-the-art research in cellular therapies and novel cell sources for these therapies is discussed. The clinically available cell-free biomaterial implants and the current progress on cell-free biomaterial implants are reviewed. Cell-based tissue engineering strategies for the repair and replacement of meniscus are presented, and the current challenges are identified. Tissue-engineered meniscal biocomposite implants may provide an alternative solution for the treatment of meniscal injury to prevent OA in the long run, because of the limitations of the existing therapies.

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Repetitive allogeneic intraarticular injections of synovial mesenchymal stem cells promote meniscus regeneration in a porcine massive meniscus defect model

Abstract: Intraarticular injections of allogeneic synovial MSCs appeared to promote meniscus regeneration and provide protection at the medial femoral articular cartilage in a porcine massive meniscal defect model.

Cited by 141 publications

References 29 publications

A study to identify and characterize the stem/progenitor cell in rabbit meniscus

A study to identify and characterize the stem/progenitor cell in rabbit meniscus

Proliferation And Differentiation Potential Of Canine Synovial Fluid Cells

Current Concepts in Meniscus Tissue Engineering and Repair

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