Not single but periodic injections of synovial MSCs maintained viable cells without losing their MSC properties in knees and inhibited osteoarthritis (OA) progression by secretion of trophic factors.
Transplantation of synovial MSCs promoted healing after meniscal repair with induction of synovium into the longitudinal tear in the avascular zone of meniscus in pigs.
Osteoarthritis (OA), a common chronic joint disorder in both humans and canines, is characterized by a progressive loss of articular cartilage. Canines can serve as an animal model of OA for human medicine, and this research can simultaneously establish effective veterinary treatments for canine OA. One attractive treatment that can lead to cartilage regeneration is the use of mesenchymal stem cells (MSCs). However, for canine OA, little information is available regarding the best source of MSCs. The purpose of this study was to identify a promising MSC source for canine cartilage regeneration. We collected synovial, infrapatellar fat pad, inguinal adipose, and bone marrow tissues from six canines and then conducted a donor-matched comparison of the properties of MSCs derived from these four tissues. We examined the surface epitope expression, proliferation capacity, and trilineage differentiation potential of all four populations. Adherent cells derived from all four tissue sources exhibited positivity for CD90 and CD44 and negativity for CD45 and CD11b. The positive rate for CD90 was higher for synovium-derived than for adipose-derived and bone marrow-derived MSCs. Synovium-derived and infrapatellar fat pad-derived MSCs displayed substantial proliferation ability, and all four populations underwent trilineage differentiation. During chondrogenesis, the wet weight was heavier for cartilage pellets derived from synovium MSCs than from the other three sources. The synovium is therefore a promising source for MSCs for canine cartilage regeneration. Our findings provide useful information about canine MSCs that may be applicable to regenerative medicine for treatment of OA.
Complex degenerative tears of the medial meniscus in the knee are usually treated using
meniscectomy. However, this procedure increases the risk of osteoarthritis, while other
treatments aimed at meniscal repair remain challenging due to the high possibility of
failure. The use of synovial mesenchymal stem cells (MSCs) is an attractive additional
approach for meniscal repair, as these cells have high proliferative and chondrogenic
potential. In this case report, we surgically repaired a complex degenerative tear of the
medial meniscus and then transplanted autologous synovial MSCs. We evaluated clinical
outcomes at 2 years and assessed adverse events. We enrolled patients with clinical
symptoms that included a feeling of instability in addition to pain caused by their
complex degenerative tears of the medial meniscus. Two weeks after surgical repair of the
torn meniscus, autologous synovial MSCs were transplanted onto the menisci of five
patients. The total Lysholm knee score, the Knee Injury and Osteoarthritis Outcome Scale
scores for “pain,” “daily living,” “sports activities,” and the Numerical Rating Scale
were significantly increased after 2 years. Three adverse events, an increase in
c-reactive protein, joint effusion, and localized warmth of the knee were recorded,
although these could have been due to the meniscal repair surgery. This first-in-human
study confirmed that the combination of surgical repair and synovial MSC transplantation
improved the clinical symptoms in patients with a complex degenerative tear of the medial
meniscus. No adverse events occurred that necessitated treatment discontinuation. These
findings will serve as pilot data for a future prospective study.
These findings suggest that in active UC, IL-4 is pivotal, in combination with other Th2-like cytokines. In contrast, Th1-like cytokines and IL-15 bear no definite relation to local inflammation of UC.
BackgroundSynovial mesenchymal stem cells (MSCs) are an attractive cell source for cartilage and meniscus regeneration. Synovial tissue can be histologically classified into three regions; surface, stromal and perivascular region, but the localization of synovial MSCs has not been fully investigated. We identified markers specific for each region, and compared properties of MSCs derived from each region in the synovium.MethodsThe intensity of immunostaining with 19 antibodies was examined for surface, stromal, and perivascular regions of human synovium from six osteoarthritis patients. Specific markers were identified and synovial cells derived from each region were sorted. Proliferation, surface marker expression, chondrogenesis, calcification and adipogenesis potentials were compared in synovial MSCs derived from the three regions.ResultsWe selected CD55+ CD271− for synovial cells in the surface region, CD55− CD271− in the stromal region, and CD55− CD271+ in the perivascular region. The ratio of the sorted cells to non-hematopoietic lineage cells was 5% in the surface region, 70% in the stromal region and 15% in the perivascular region. Synovial cells in the perivascular fraction had the greatest proliferation potential. After expansion, surface marker expression profiles and adipogenesis potentials were similar but chondrogenic and calcification potentials were higher in synovial MSCs derived from the perivascular region than in those derived from the surface and stromal regions.ConclusionsWe identified specific markers to isolate synovial cells from the surface, stromal, and perivascular regions of the synovium. Synovial MSCs in the perivascular region had the highest proliferative and chondrogenic potentials among the three regions.
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