Mesenchymal stem cells for cartilage engineering

Huselstein, Céline; Li, Yi; He, Xia

doi:10.3233/bme-2012-0691

Cited by 23 publications

(23 citation statements)

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“…Thus, various authors have attempted to isolate MSCs from adipose tissue, 11 dental tissues (pulp and periodontal ligament, dental follicle, apical papilla, and deciduous teeth), [12][13][14][15][16][17][18] oral tissues (gingiva and oral mucosa), 19 umbilical cord, 20,21 synovial membrane and synovial fluid, 22 periosteum, 23 trabecular bone, 23 dermis, 24 infrapatellar fat pad, 25 and articular cartilage. 26 The addition of supporting growth or differentiation factors has become particularly relevant to enhance the osteogenic function of MSCs. [27][28][29][30] Bone morphogenetic proteins (BMPs), which belong to the transforming growth factor (TGF)-b superfamily, are multifunctional differentiation factors.…”

Section: Introductionmentioning

confidence: 99%

Bone morphogenetic protein‐2, ‐6, and ‐7 differently regulate osteogenic differentiation of human periodontal ligament stem cells

et al. 2013

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The utility of adult stem cells for bone regeneration may be an attractive alternative in the treatment of extensive injury, congenital malformations, or diseases causing large bone defects. To create an environment that is supportive of bone formation, signals from molecules such as the bone morphogenetic proteins (BMPs) are required to engineer fully viable and functional bone. We therefore determined whether BMP-2, -6, and -7 differentially regulate the (1) proliferation, (2) mineralization, and (3) mRNA expression of bone/mineralized tissue associated genes of human periodontal ligament stem cells (hPDLSCs), which were obtained from periodontal ligament tissue of human impacted third molars. hPDLSCs from six participants were isolated and characterized using histochemical and immunohistochemical methods. A real-time cell analyzer was used to evaluate the effects of BMP-2, -6, and -7 on the proliferation of hPDLSCs. hPDLSCs were treated with Dulbecco's modified Eagle's medium containing different concentrations of BMP-2, -6, and -7 (10, 25, 50, 100 ng/mL) and monitored for 264 hours. After dose-response experiments, 50 and 100 ng/mL concentrations of BMPs were used to measure bone/mineralized tissue-associated gene expression. Type I collagen, bone sialoprotein, osteocalcin, osteopontin, and osteoblastic transcription factor Runx2 mRNA expression of hPDLSCs treated with BMP-2, -6, and -7, were evaluated using quantitative RT-PCR. Biomineralization of hPDLSCs was assessed using von Kossa staining. This study demonstrated that BMPs at various concentrations differently regulate the proliferation, mineralization, and mRNA expression of bone/mineralized tissue associated genes in hPDLSCs. BMPs regulate hPDLSC proliferation in a time and dose-dependent manner when compared to an untreated control group. BMPs induced bone/mineralized tissue-associated gene mRNA expression and biomineralization of hPDLSCs. The most pronounced induction occurred in the BMP-6 group in the biomineralization of the hPDLSCs. Our data suggest that BMP-2, -6, and -7 are potent regulators of hPDLSC gene expression and biomineralization. Employing BMPs with hPDLSCs isolated from periodontal ligament tissues provides a promising strategy for bone tissue engineering.

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Section: Introductionmentioning

confidence: 99%

Bone morphogenetic protein‐2, ‐6, and ‐7 differently regulate osteogenic differentiation of human periodontal ligament stem cells

et al. 2013

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“…The proliferation of hMSCs and hACs as 3D aggregates in serum-free suspension culture demonstrates that scalable bioreactors represent an accessible platform capable of supporting the generation of clinical quantities of cells for use in cell-based cartilage repair. the presence of hyaline cartilage, a complex, three-dimensional (3D) extracellular matrix of collagen II and proteoglycans, which houses articular chondrocytes (ACs; Csaki, Schneider, & Shakibaei, 2008;Dhinsa & Adesida, 2012;Huselstein, Li, & He, 2012;Vinatier, Mrugala, Jorgensen, Guicheux, & Noël, 2009). Defects in articular (hyaline) cartilage, as a result of injury or wear and tear, can initiate a progressive, degenerative process that can eventually lead to osteoarthritis (OA), a chronic and debilitating medical condition that affects 25% of adults over 50 years of age (Schulz & Bader, 2007).…”

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confidence: 99%

“…Because articular cartilage is avascular and has a very limited capacity for spontaneous self-repair, clinical interventions, such as microfracture and cartilage grafting, have been developed to facilitate repair. However, microfracture results in the formation of fibrocartilage, which has ABBREVIATIONS: 2D, Two-dimensional; 3D, Three-dimensional; AC, Articular chondrocyte; COMP, Cartilage oligomeric matrix protein; DMEM, Dulbecco's modified Eagle's medium; DNA, Deoxyribonucleic acid; EDTA, Ethylenediaminetetraacetic acid; FBS, Fetal bovine serum; GAG, Glycosaminoglycan; hAC, Human articular chondrocyte; HEPES, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid; hMSC, Human mesenchymal stem cell; MSC, Mesenchymal stem cell; OA, Osteoarthritis; p(number), Passage (number); PBS, Phosphate-buffered saline; PenStrep, Penicillin and streptomycin solution; RNA, Ribonucleic acid; SCM, Serum-containing medium; SFM, Serum-free medium; T-flask, Tissue culture flask; TGF-β, Transforming growth factor β; αMEM, Modified Eagle's medium α significantly inferior biomechanical properties compared with articular cartilage, and grafts are limited by poor integration with the native tissue (Dhinsa & Adesida, 2012;Huselstein et al, 2012;Vinatier et al, 2009). Thus, alternative approaches have emerged.…”

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confidence: 99%

“…Due to the paucity of ACs in articular cartilage (12-16 million chondrocytes/g tissue; Jakob et al, 2003) and low post-isolation yields (<22%; Jakob et al, 2003), chondrocytes are typically expanded in culture to obtain clinically relevant cell numbers (2.6-5 million cells for typical focal defect sizes of 1.6-6.5 cm 2 ; Brittberg et al, 1994). Following monolayer (2D) cell culture, the expanded chondrocytes are then reintroduced into the defect site, either in a scaffold or with a membrane, in an attempt to regenerate hyaline cartilage (Csaki et al, 2008;Dhinsa & Adesida, 2012;Huselstein et al, 2012). In contrast to treating focal defects, autologous chondrocyte treatment of OA cartilage necessitates restoration of larger surfaces of "at least 25 cm 2 " (Tallheden et al, 2005).…”

mentioning

confidence: 99%

“…Whereas ACI has shown some clinical success (Huselstein et al, 2012), it suffers from a number of problems. The chondrocytes serially expanded in monolayer undergo replicative senescence and dedifferentiate, exhibiting decreased production of collagen II and aggrecan, and increased production of collagen I (Csaki et al, 2008;Hardingham, Tew, & Murdoch, 2002;Huselstein et al, 2012;Vinatier et al, 2009). Furthermore, certain long-term complications of ACI, such as graft hypertrophy, have been linked to prior cell culture methods (Studer, Millan, Oeztuerk, Maniura-Weber, & Zenobi-Wong, 2012).…”

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confidence: 99%

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Osteoarthritic human chondrocytes proliferate in 3D co‐culture with mesenchymal stem cells in suspension bioreactors

Khurshid

Mulet‐Sierra

Adesida

et al. 2017

J Tissue Eng Regen Med

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Osteoarthritis (OA) is a painful disease, characterized by progressive surface erosion of articular cartilage. The use of human articular chondrocytes (hACs) sourced from OA patients has been proposed as a potential therapy for cartilage repair, but this approach is limited by the lack of scalable methods to produce clinically relevant quantities of cartilage-generating cells. Previous studies in static culture have shown that hACs co-cultured with human mesenchymal stem cells (hMSCs) as 3D pellets can upregulate proliferation and generate neocartilage with enhanced functional matrix formation relative to that produced from either cell type alone. However, because static culture flasks are not readily amenable to scale up, scalable suspension bioreactors were investigated to determine if they could support the co-culture of hMSCs and OA hACs under serum-free conditions to facilitate clinical translation of this approach. When hACs and hMSCs (1:3 ratio) were inoculated at 20,000 cells/ml into 125-ml suspension bioreactors and fed weekly, they spontaneously formed 3D aggregates and proliferated, resulting in a 4.75-fold increase over 16 days. Whereas the apparent growth rate was lower than that achieved during co-culture as a 2D monolayer in static culture flasks, bioreactor co-culture as 3D aggregates resulted in a significantly lower collagen I to II mRNA expression ratio and more than double the glycosaminoglycan/DNA content (5.8 vs. 2.5 μg/μg). The proliferation of hMSCs and hACs as 3D aggregates in serum-free suspension culture demonstrates that scalable bioreactors represent an accessible platform capable of supporting the generation of clinical quantities of cells for use in cell-based cartilage repair.

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Synthesis of monolithic HPLC stationary phase with self‐assembled molecular recognition sites for 4‐aminophenol

Baykara

Tunc

Ulubayram

2011

J of Applied Polymer Sci

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A molecularly imprinted polymer (MIP) monolith for selective recognition of 4-aminophenol (4-AMP) was prepared by in situ polymerization technique as high-performance liquid chromatography (HPLC) stationary phase. For this purpose, several 4-AMP imprinted monoliths were synthesized by using only methacrylic acid (MAA), acrylamide (AAM), or isobornyl methacrylate (IBMA) in the presence of high amount of crosslinker, ethylene glycol dimethacrylate (EDMA), and these polymeric monolith columns were connected to HPLC to evaluate their separation capabilities. By selection of appropriate functional monomer and optimization of polymerization conditions, MAA-based monolithic MIP showed good flow through properties, high selectivity to the templated molecule, and high resolution in the separation of paracetamol and its main impurity, 4-AMP. Besides, effective binding site density and dissociation constant of this monolith were estimated by using frontal chromatography and found as 7.95 lmol/g and 1.06 mM, respectively. Surface area of the same monolith was found as 23.48 m 2 /g from multipoint BET analysis.

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Mesenchymal stem cells for cartilage engineering

Cited by 23 publications

References 0 publications

Bone morphogenetic protein‐2, ‐6, and ‐7 differently regulate osteogenic differentiation of human periodontal ligament stem cells

Bone morphogenetic protein‐2, ‐6, and ‐7 differently regulate osteogenic differentiation of human periodontal ligament stem cells

Osteoarthritic human chondrocytes proliferate in 3D co‐culture with mesenchymal stem cells in suspension bioreactors

Synthesis of monolithic HPLC stationary phase with self‐assembled molecular recognition sites for 4‐aminophenol

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