Age-dependent decrease in the chondrogenic potential of human bone marrow mesenchymal stromal cells expanded with fibroblast growth factor-2

Kanawa, Masami; Igarashi, Akira; Ronald, Veronica Sainik; Higashi, Yukihito; Kurihara, Hidemi; Sugiyama, Masaru; Saskianti, Tania; Pan, Hong; Kato, Yukio

doi:10.1016/j.jcyt.2013.03.015

Cited by 49 publications

(42 citation statements)

References 37 publications

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“…25 Zaim et al 26 found that the adipogenic, osteogenic, and neurogenic differentiation potentials of hBMSCs declined with age, but that the chondrogenic potential did not. In contrast, Kanawa et al 27 reported that the adipogenic and osteogenic differentiation capacities of human BMSCs were unaffected by age, but the chondrogenic capacity of BMSCs declined with age. We used 3 volunteers as sources of BMSCs in the present study with an average age of 26 years.…”

Section: Discussionmentioning

confidence: 90%

Transplantation of Scaffold-Free Cartilage-Like Cell-Sheets Made from Human Bone Marrow Mesenchymal Stem Cells for Cartilage Repair

et al. 2016

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Objective The object of this study was to determine culture conditions that create stable scaffold-free cartilage-like cell-sheets from human bone marrow–derived mesenchymal stem cells (hBMSCs) and to assess their effects after transplantation into osteochondral defects in nude rats. Design (Experiment 1) The hBMSCs were harvested from 3 males, the proliferative and chondrogenic capacities were assessed at passage 1, and the cells were expanded in 3 different culture conditions: (1) 5% fetal bovine serum (FBS), (2) 10% FBS, and (3) 5% FBS with fibroblast growth factor 2 (FGF-2). The cells were harvested and made chondrogenic pellet culture. The cell proliferation rate, glycosaminoglycan/DNA ratio, and safranin-O staining intensity of pellets cultured condition 3 were higher than those of conditions 1 and 2. (Experiment 2) The hBMSCs were expanded and passaged 3 times under culture condition 3, and fabricate the cell-sheets in chondrogenic medium either with or without FBS. The cell-sheets fabricated with FBS maintained their size with flat edges. (Experiment 3) The cell-sheets were transplanted into osteochondral defects in nude rats. Histological analysis was performed at 2, 4, and 12 weeks after surgery. Results The osteochondral repair was better after sheet transplantation than in the control group and significantly improved Wakitani score. Immunostaining with human-specific vimentin antibody showed that the transplanted cells became fewer and disappeared at 12 weeks. Conclusions These results indicate that culture with FGF-2 may help to quickly generate sufficient numbers of cells to create stable and reliable scaffold-free cartilage-like cell-sheets, which contribute to the regeneration of osteochondral defects.

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Section: Discussionmentioning

confidence: 90%

Transplantation of Scaffold-Free Cartilage-Like Cell-Sheets Made from Human Bone Marrow Mesenchymal Stem Cells for Cartilage Repair

et al. 2016

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“…47 Increased age has also been shown to reduce the chondrogenic potential of human MSCs. 48 Recent studies have shown that allogeneic MSCs can be used in humans without increased complication rates, and some companies have marketed allogeneic juvenile chondrocytes for cartilage repair (DeNovo Ò ; Zimmer, Inc.). The ultimate application of this technology may involve the use of allogeneic MSCs.…”

Section: Discussionmentioning

confidence: 99%

Anatomic Mesenchymal Stem Cell-Based Engineered Cartilage Constructs for Biologic Total Joint Replacement

Saxena

Kim

Keah

et al. 2016

Tissue Engineering Part A

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Cartilage has a poor healing response, and few viable options exist for repair of extensive damage. Hyaluronic acid (HA) hydrogels seeded with mesenchymal stem cells (MSCs) polymerized through UV crosslinking can generate functional tissue, but this crosslinking is not compatible with indirect rapid prototyping utilizing opaque anatomic molds. Methacrylate-modified polymers can also be chemically crosslinked in a cytocompatible manner using ammonium persulfate (APS) and N,N,N¢,N¢-tetramethylethylenediamine (TEMED). The objectives of this study were to (1) compare APS/TEMED crosslinking with UV crosslinking in terms of functional maturation of MSC-seeded HA hydrogels; (2) generate an anatomic mold of a complex joint surface through rapid prototyping; and (3) grow anatomic MSC-seeded HA hydrogel constructs using this alternative crosslinking method. Juvenile bovine MSCs were suspended in methacrylated HA (MeHA) and crosslinked either through UV polymerization or chemically with APS/TEMED to generate cylindrical constructs. Minipig porcine femoral heads were imaged using microCT, and anatomic negative molds were generated by threedimensional printing using fused deposition modeling. Molded HA constructs were produced using the APS/ TEMED method. All constructs were cultured for up to 12 weeks in a chemically defined medium supplemented with TGF-b3 and characterized by mechanical testing, biochemical assays, and histologic analysis. Both UV-and APS/TEMED-polymerized constructs showed increasing mechanical properties and robust proteoglycan and collagen deposition over time. At 12 weeks, APS/TEMED-polymerized constructs had higher equilibrium and dynamic moduli than UV-polymerized constructs, with no differences in proteoglycan or collagen content. Molded HA constructs retained their hemispherical shape in culture and demonstrated increasing mechanical properties and proteoglycan and collagen deposition, especially at the edges compared to the center of these larger constructs. Immunohistochemistry showed abundant collagen type II staining and little collagen type I staining. APS/TEMED crosslinking can be used to produce MSC-seeded HA-based neocartilage and can be used in combination with rapid prototyping techniques to generate anatomic MSC-seeded HA constructs for use in filling large and anatomically complex chondral defects or for biologic joint replacement.

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“…24 Kanawa and colleagues, however, reported that the adipogenic and osteogenic differentiation capacities of human BMSCs were unchanged by age, but that BMSCs' chondrogenic capacity declined. 34 As has been reviewed elsewhere, 35 molecular differences between young and aged MSCs likely partially account for the phenotypic differences between youthful and aged stem cells. Approximately 8000 genes were differentially expressed between murine (C57BL/6 WT) BMSCs from 2-, 8-, and 26-month-old sources.…”

Section: Donor Age Dependent Cell Senescencementioning

confidence: 99%

Age associated communication between cells and matrix: a potential impact on stem cell-based tissue regeneration strategies

Lynch

Pei²

2014

Organogenesis

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A recent paper demonstrated that decellularized extracellular matrix (DECM) deposited by synovium-derived stem cells (SDSCs), especially from fetal donors, could rejuvenate human adult SDSCs in both proliferation and chondrogenic potential, in which expanded cells and corresponding culture substrate (such as DECM) were found to share a mutual reaction in both elasticity and protein profiles (see ref.

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Age-dependent decrease in the chondrogenic potential of human bone marrow mesenchymal stromal cells expanded with fibroblast growth factor-2

Cited by 49 publications

References 37 publications

Transplantation of Scaffold-Free Cartilage-Like Cell-Sheets Made from Human Bone Marrow Mesenchymal Stem Cells for Cartilage Repair

Transplantation of Scaffold-Free Cartilage-Like Cell-Sheets Made from Human Bone Marrow Mesenchymal Stem Cells for Cartilage Repair

Anatomic Mesenchymal Stem Cell-Based Engineered Cartilage Constructs for Biologic Total Joint Replacement

Age associated communication between cells and matrix: a potential impact on stem cell-based tissue regeneration strategies

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