K Sivasubramaniyan1, W J L M Koevoet2, A A Hakimiyan3, M Sande1, E Farrell4, M J Hoogduijn5, J A N Verhaar1, S Chubinskaya3, H-J Bühring6, G J V M van Osch7. 1. Department of Orthopaedics, Erasmus MC University Medical Center, Rotterdam, the Netherlands. 2. Department of Otorhinolaryngology, Erasmus MC University Medical Center, Rotterdam, the Netherlands. 3. Department of Pediatrics, Rush University Medical Center, Chicago, IL, USA. 4. Department of Oral and Maxillofacial Surgery, Special Dental Care and Orthodontics, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands. 5. Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands. 6. Department of Internal Medicine II, Division of Hematology, University Clinic of Tübingen, Tübingen, Germany. 7. Department of Orthopaedics, Erasmus MC University Medical Center, Rotterdam, the Netherlands; Department of Otorhinolaryngology, Erasmus MC University Medical Center, Rotterdam, the Netherlands. Electronic address: g.vanosch@erasmusmc.nl.
Abstract
OBJECTIVE: Synovium contains multipotent progenitor/stromal cells (MPCs) with potential to participate in cartilage repair. Understanding the identity of these MPCs will allow their therapeutic potential to be fully exploited. Hence this study aimed to identify primary synovial MPCs and characterize them in the context of cartilage regeneration. METHODS: Primary MPC/MPC-subset specific markers in synovium were identified by FACS analysis of uncultured cells. MPC-subsets from human synovium obtained from patients undergoing total knee arthroplasty were FACS sorted, cultured, immunophenotyped and chondrogenically differentiated. The anatomical localization of MPCs in synovium was examined using immunohistochemistry. Finally, the presence of these MPC subsets in healthy synovium obtained from human organ donors was examined. RESULTS: A combination of CD45, CD31, CD73 and CD90 can isolate two distinct MPC-subsets in synovium. These MPC-subsets, freshly isolated from synovium, did not express CD45 or CD31, but expressed CD73. Additionally, a sub-population of CD73+ cells also expressed CD90. CD45-CD31-CD73+CD90- cells were significantly more chondrogenic than CD45-CD31-CD73+CD90+ cells in the presence of TGFβ1. Interestingly, reduced chondrogenic ability of CD73+CD90+ cells could be reversed by the addition of BMP2, showing discrete chondrogenic factor requirements by distinct cell-subsets. In addition, these MPCs had distinct anatomical localization; CD73 was expressed both in intimal and sub-intimal region while CD90 was enriched in the sub-intimal region. We further demonstrated that these subsets are also present in healthy synovium. CONCLUSIONS: We provide indications that primary MPCs in synovial intima and sub-intima are phenotypically and functionally distinct with different chondrogenic properties.
OBJECTIVE: Synovium contains multipotent progenitor/stromal cells (MPCs) with potential to participate in cartilage repair. Understanding the identity of these MPCs will allow their therapeutic potential to be fully exploited. Hence this study aimed to identify primary synovial MPCs and characterize them in the context of cartilage regeneration. METHODS: Primary MPC/MPC-subset specific markers in synovium were identified by FACS analysis of uncultured cells. MPC-subsets from human synovium obtained from patients undergoing total knee arthroplasty were FACS sorted, cultured, immunophenotyped and chondrogenically differentiated. The anatomical localization of MPCs in synovium was examined using immunohistochemistry. Finally, the presence of these MPC subsets in healthy synovium obtained from human organ donors was examined. RESULTS: A combination of CD45, CD31, CD73 and CD90 can isolate two distinct MPC-subsets in synovium. These MPC-subsets, freshly isolated from synovium, did not express CD45 or CD31, but expressed CD73. Additionally, a sub-population of CD73+ cells also expressed CD90. CD45-CD31-CD73+CD90- cells were significantly more chondrogenic than CD45-CD31-CD73+CD90+ cells in the presence of TGFβ1. Interestingly, reduced chondrogenic ability of CD73+CD90+ cells could be reversed by the addition of BMP2, showing discrete chondrogenic factor requirements by distinct cell-subsets. In addition, these MPCs had distinct anatomical localization; CD73 was expressed both in intimal and sub-intimal region while CD90 was enriched in the sub-intimal region. We further demonstrated that these subsets are also present in healthy synovium. CONCLUSIONS: We provide indications that primary MPCs in synovial intima and sub-intima are phenotypically and functionally distinct with different chondrogenic properties.
Authors: Jiapeng Xue; Jinnan Chen; Quan Shen; Deva Chan; Jun Li; Adam P Tanguay; Tannin A Schmidt; Faizan Niazi; Anna Plaas Journal: Cells Date: 2020-07-13 Impact factor: 6.600
Authors: M Teunissen; N S Ahrens; L Snel; R Narcisi; S A Kamali; G J V M van Osch; B P Meij; S C Mastbergen; K Sivasubramaniyan; M A Tryfonidou Journal: Stem Cell Res Ther Date: 2022-09-05 Impact factor: 8.079
Authors: Michella H Hagmeijer; Jasmijn V Korpershoek; João F Crispim; Li-Ting Chen; Pascal Jonkheijm; Aaron J Krych; Daniel B F Saris; Lucienne A Vonk Journal: J Tissue Eng Regen Med Date: 2021-05-21 Impact factor: 3.963