The lower in vitro chondrogenic potential of canine adipose tissue-derived mesenchymal stromal cells (MSC) compared to bone marrow-derived MSC is not improved by BMP-2 or BMP-6

Teunissen, M.; Verseijden, Femke; Riemers, Frank M.; Osch, Gerjo J.V.M. van; Tryfonidou, Marianna A.

doi:10.1016/j.tvjl.2020.105605

Cited by 14 publications

(9 citation statements)

References 42 publications

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“…Tri-lineage differentiation of the cSM-MSCs was performed in P2 as per methods described previously [ 23 ], with some small adaptations. For chondrogenic differentiation, normal ( n = 7) and OA ( n = 8) P2 cSM-MSCs were cultured in pellets of 100.000 cells/well in a 96-well plate (Corning® Costar® 7007) in chondrogenic differentiation medium (DMEM high glucose (31966, Invitrogen), 1% p/s, 1% ITS + Premix, 0.04 mg/mL proline (P5607, Sigma), 0.1 mM AsAP and 10 –7 M dexamethasone (D1756, Sigma)) with the addition of 10 ng/mL recombinant human transforming growth factor-β1 (TGF-β1; 240-B, R&D Systems, Minneapolis, USA) and 100 ng/mL recombinant human bone morphogenetic protein-2 (BMP-2; 355-BM, R&D systems).…”

Section: Methodsmentioning

confidence: 99%

Synovial membrane-derived mesenchymal progenitor cells from osteoarthritic joints in dogs possess lower chondrogenic-, and higher osteogenic capacity compared to normal joints

et al. 2022

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Background Synovial membrane-derived mesenchymal progenitor cells (SM-MPCs) are a promising candidate for the cell-based treatment of osteoarthritis (OA) considering their in vitro and in vivo capacity for cartilage repair. However, the OA environment may adversely impact their regenerative capacity. There are no studies for canine (c)SM-MPCs that compare normal to OA SM-MPCs, even though dogs are considered a relevant animal model for OA. Therefore, this study compared cSM-MPCs from normal and OA synovial membrane tissue to elucidate the effect of the OA environment on MPC numbers, indicated by CD marker profile and colony-forming unit (CFU) capacity, and the impact of the OA niche on tri-lineage differentiation. Methods Normal and OA synovial membrane were collected from the knee joints of healthy dogs and dogs with rupture of the cruciate ligaments. The synovium was assessed by histopathological OARSI scoring and by RT-qPCR for inflammation/synovitis-related markers. The presence of cSM-MPCs in the native tissue was further characterized with flow cytometry, RT-qPCR, and immunohistochemistry, using the MPC markers; CD90, CD73, CD44, CD271, and CD34. Furthermore, cells isolated upon enzymatic digestion were characterized by CFU capacity, and a population doublings assay. cSM-MPCs were selected based on plastic adherence, expanded to passage 2, and evaluated for the expression of MPC-related surface markers and tri-lineage differentiation capacity. Results Synovial tissue collected from the OA joints had a significantly higher OARSI score compared to normal joints, and significantly upregulated inflammation/synovitis markers S100A8/9, IL6, IL8, and CCL2. Both normal and OA synovial membrane contained cells displaying MPC properties, including a fibroblast-like morphology, CFU capacity, and maintained MPC marker expression over time during expansion. However, OA cSM-MPCs were unable to differentiate towards the chondrogenic lineage and had low adipogenic capacity in contrast to normal cSM-MPCs, whereas they possessed a higher osteogenic capacity. Furthermore, the OA synovial membrane contained significantly lower percentages of CD90+, CD44+, CD34+, and CD271+ cells. Conclusions The OA environment had adverse effects on the regenerative potential of cSM-MPCs, corroborated by decreased CFU, population doubling, and chondrogenic capacity compared to normal cSM-MPCs. OA cSM-MPCs may be a less optimal candidate for the cell-based treatment of OA than normal cSM-MPCs.

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Section: Methodsmentioning

confidence: 99%

Synovial membrane-derived mesenchymal progenitor cells from osteoarthritic joints in dogs possess lower chondrogenic-, and higher osteogenic capacity compared to normal joints

et al. 2022

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“…No significant increase in GAG and DNA levels was noted in the chondrocyte aggregates stimulated with TGF-β, compared to the basal culture conditions. Why TGF-β did not enhance GAG production is unclear, but it could be due to insensitivity of canine articular chondrocytes to TGF-β as the sole chondrogenic stimulant, as was found recently in canine adipose tissue-derived mesenchymal stem cells, or due to environmental factors during culture [55].…”

Section: Discussionmentioning

confidence: 90%

Intra-Articular Slow-Release Triamcinolone Acetonide from Polyesteramide Microspheres as a Treatment for Osteoarthritis

et al. 2021

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Osteoarthritis (OA) is a common cause of pain and disability. Local corticosteroid injections are effective in treating OA pain and inflammation but are short-acting. Prolonged intra-articular (IA) corticosteroid exposure may even lead to cartilage deterioration. The aim of this prospective study was to assess safety and provide proof-of-concept of IA-applied biodegradable polyesteramide-based microspheres (PEAMs) gradually releasing triamcinolone acetonide (TA). Mimicking continuous exposure associated with local drug delivery in canine articular chondrocytes cultured in the continuous presence of TA tissue regeneration was not affected, whereas intermittent exposure reduced proteoglycan production. In this respect, TA-PEAMs administered IA in a proof-of-concept study in 12 client-owned dogs with established OA also showed safety by radiographic examination, without changes in OA severity and in glycosaminoglycan synovial fluid levels. Treatment also resulted in clinical improvement in 10 out of 11 dogs during the two-month follow-up period, which persisted in 6 out of 10 dogs after 6 months, based on objective gait analysis and owner questionnaires. Synovial prostaglandin E2, a pro-inflammatory marker, was decreased two months after treatment. This study showed safety and proof-of-concept of IA-administered TA-PEAMs in dogs with OA, as a first step towards translation into the veterinary and human clinic.

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“…However, the limitation is that we do not know what specific agents were included as media supplements. One may assume that growth factors such as TGFβ would be included as well as dexamethasone but further studies are essential to examine the role of individual growth factors such as bone morphogenetic protein (BMPs) or TGFβ1 versus TGFβ3 would have in enhancing induction, 31 particularly in light of our data that show induction-associated BMP gene expression changes in the placental MSCs.…”

Section: Discussionmentioning

confidence: 99%

The Chondrogenic Potential of First-Trimester and Term Placental Mesenchymal Stem/Stromal Cells

et al. 2021

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Objectives Mesenchymal stem/stromal cells (MSCs) are a well-established cell source for cartilage engineering, but challenges remain as differentiation often results in chondrocyte hypertrophy. Chondrogenic potential also varies with MSC source and donor age. We assessed the chondrogenic potential of first-trimester and term placental MSCs and compared their response to commonly used bone marrow MSCs (BM-MSCs). Design MSCs were isolated from first-trimester and term placentae. BM-MSCs were commercially obtained. Chondrogenesis was induced by micromass culture in commercial chondrogenic media for 7, 14, or 21 days. Pellets were assessed for glycosaminoglycan (GAG) content, and types I, II, and X collagen. Gene expression was profiled using Qiagen RT2 human MSC arrays. Results At day 0, first-trimester and term MSCs expression levels of many chondrogenic genes to BM-MSC after 21 days of culture. Only first trimester MSCs showed significant changes in chondrogenic gene expression during induction compared to day 0 undifferentiated MSCs (greater BMP4, KAT2B, and reduced GDF6 expression). Additionally, first-trimester MSCs showed significantly greater expression of ABCB1 (at days 14 and 21) and BMP4 (at days 7, 14, 21) compared with term MSCs. Both first-trimester and term pellets showed increased GAG content over time and term MSCs had significantly GAG greater compared with BM-MSCs at days 7 and 14. Type II collagen was present in all pellets but unlike BM-MSCs, type I collagen was not observed in first-trimester or term MSC pellets. Conclusions These data highlight differences in BM-MSC and placental MSC chondrogenesis and demonstrate that placental MSCs may be an alternative cell source.

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The lower in vitro chondrogenic potential of canine adipose tissue-derived mesenchymal stromal cells (MSC) compared to bone marrow-derived MSC is not improved by BMP-2 or BMP-6

Cited by 14 publications

References 42 publications

Synovial membrane-derived mesenchymal progenitor cells from osteoarthritic joints in dogs possess lower chondrogenic-, and higher osteogenic capacity compared to normal joints

Synovial membrane-derived mesenchymal progenitor cells from osteoarthritic joints in dogs possess lower chondrogenic-, and higher osteogenic capacity compared to normal joints

Intra-Articular Slow-Release Triamcinolone Acetonide from Polyesteramide Microspheres as a Treatment for Osteoarthritis

The Chondrogenic Potential of First-Trimester and Term Placental Mesenchymal Stem/Stromal Cells

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