Fibroblast Growth Factor-2 Enhances Proliferation and Delays Loss of Chondrogenic Potential in Human Adult Bone-Marrow-Derived Mesenchymal Stem Cells

Solchaga, Luis A.; Penick, Kitsie; Goldberg, Victor M.; Caplan, Arnold I.; Welter, Jean F.

doi:10.1089/ten.tea.2009.0100

Cited by 175 publications

(182 citation statements)

References 52 publications

(70 reference statements)

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“…This study develops upon previous work to ascertain if such expansion conditions, specifically expansion in the presence of FGF-2, could further enhance the mechanical functionality of cartilaginous constructs engineered using IFP derived MSCs. The observed beneficial effects of expanding in the presence of FGF-2 is consistent with previous findings for other sources of stem cells in terms of more rapid proliferation and improved chondrogenic potential evident by increased levels of matrix synthesis (Solchaga et al 2005;Khan et al 2008;Solchaga et al 2010). After 3 weeks of in vitro culture, IFP derived MSCs expanded in the presence of FGF-2 generated cartilaginous grafts whose mechanical functionality was at least comparable to that which we have previously reported using other cell types from the same species at the same time point (Thorpe et al 2008;Buckley et al 2010a;Meyer et al 2010;Thorpe et al 2010;Vinardell et al 2010).…”

Section: Discussionsupporting

confidence: 89%

“…It is evident from the literature that stem cell expansion conditions can significantly influence their subsequent chondrogenic capacity (Tsutsumi et al 2001;Bianchi et al 2003;Solchaga et al 2005;Khan et al 2008;Solchaga et al 2010). This study develops upon previous work to ascertain if such expansion conditions, specifically expansion in the presence of FGF-2, could further enhance the mechanical functionality of cartilaginous constructs engineered using IFP derived MSCs.…”

Section: Discussionmentioning

confidence: 99%

“…The chondrogenic capacity of MSCs can also be diminished due to the in vitro expansion conditions affecting stemness and accelerating senescence (Solchaga et al 2010). Augmenting MSC expansion conditions to enhance proliferation kinetics while maintaining multipotency is a critical obstacle to overcome in order to engineer mechanically functional tissues for clinical applications.…”

Section: Introductionmentioning

confidence: 99%

“…Augmenting MSC expansion conditions to enhance proliferation kinetics while maintaining multipotency is a critical obstacle to overcome in order to engineer mechanically functional tissues for clinical applications. Fibroblast growth factor-2 (FGF-2, also known as basic fibroblast growth factor) has been shown to be a potent stimulator during ex vivo expansion of both chondrocytes (Kato and Gospodarowicz 1985;Martin et al 1999;Martin et al 2001;Veilleux and Spector 2005) and MSCs (Banfi et al 2000;Mastrogiacomo et al 2001;Tsutsumi et al 2001;Bianchi et al 2003;Solchaga et al 2005;Khan et al 2008;Solchaga et al 2010), as well as regulating subsequent differentiation potential. Specifically, bone marrow derived MSCs cultured in the presence of FGF-2 have been shown to be physically smaller and proliferate more rapidly during monolayer expansion (Solchaga et al 2005).…”

Section: Introductionmentioning

confidence: 99%

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Expansion in the presence of FGF-2 enhances the functional development of cartilaginous tissues engineered using infrapatellar fat pad derived MSCs

Buckley

Kelly

2012

Journal of the Mechanical Behavior of Biomedical Materials

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A bstractMSCs from non-cartilaginous knee joint tissues such as the infrapatellar fat pad (IFP) and synovium possess significant chondrogenic potential and provide a readily available and clinically feasible source of chondroprogenitor cells. Fibroblast growth factor-2 (FGF-2) has been shown to be a potent mitotic stimulator during ex vivo expansion of MSCs, as well as regulating their subsequent differentiation potential.The objective of this study was to investigate the longer term effects of FGF-2 expansion on the functional development of cartilaginous tissues engineered using MSCs derived from the IFP. IFP MSCs were isolated and expanded to passage 2 in a standard media formulation with or without FGF-2 (5ng/ml) supplementation.Expanded cells were encapsulated in agarose hydrogels, maintained in chondrogenic media for 42 days and analysed to determine their mechanical properties and biochemical composition. Culture media, collected at each feed, was also analysed for biochemical constituents.MSCs expanded in the presence of FGF-2 proliferated more rapidly, with higher cell yields and lower population doubling times. FGF-2 expanded MSCs generated the most mechanically functional tissue. Matrix accumulation was dramatically higher after 21 days for FGF-2 expanded MSCs, but decreased between day 21 and 42. By day 42, FGF-2 expanded MSCs had still accumulated ~1.4 fold higher sGAG and ~1.7 fold higher collagen compared to control groups. The total amount of sGAG synthesised (retained in hydrogels and released into the media) was ~ 2.4 fold higher for FGF-2 expanded MSCs, with only ~25% of the total amount generated being retained within the constructs. Further studies are required to investigate whether IFP derived MSCs have a diminished capacity to synthesise other matrix components important in the aggregation, assembly and retention of proteoglycans. In conclusion, expanding MSCs in the presence of FGF-2 rapidly accelerates chondrogenesis in 3D agarose cultures resulting in superior mechanical functionality.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Expansion in the presence of FGF-2 enhances the functional development of cartilaginous tissues engineered using infrapatellar fat pad derived MSCs

Buckley

Kelly

2012

Journal of the Mechanical Behavior of Biomedical Materials

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“…These cells can be expanded indefinitely in an undifferentiated state, enabling the derivation of adequate numbers of differentiated progeny for high-throughput analysis and drug screening. In contrast, most adult stem cells such as MSCs and ASCs show changes in differentiation potential after ∼4 passages in culture (33). Derivation of iPSCs from minimally invasive sources such as skin fibroblasts or from joint cells during surgery allows for patient-matched engineered tissues even from elderly patients or those with OA (28,31).…”

Section: Discussionmentioning

confidence: 99%

Cartilage tissue engineering using differentiated and purified induced pluripotent stem cells

Diekman

Christoforou

Willard

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

232

250

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The development of regenerative therapies for cartilage injury has been greatly aided by recent advances in stem cell biology. Induced pluripotent stem cells (iPSCs) have the potential to provide an abundant cell source for tissue engineering, as well as generating patient-matched in vitro models to study genetic and environmental factors in cartilage repair and osteoarthritis. However, both cell therapy and modeling approaches require a purified and uniformly differentiated cell population to predictably recapitulate the physiological characteristics of cartilage. Here, iPSCs derived from adult mouse fibroblasts were chondrogenically differentiated and purified by type II collagen (Col2)-driven green fluorescent protein (GFP) expression. Col2 and aggrecan gene expression levels were significantly up-regulated in GFP+ cells compared with GFP− cells and decreased with monolayer expansion. An in vitro cartilage defect model was used to demonstrate integrative repair by GFP+ cells seeded in agarose, supporting their potential use in cartilage therapies. In chondrogenic pellet culture, cells synthesized cartilagespecific matrix as indicated by high levels of glycosaminoglycans and type II collagen and low levels of type I and type X collagen. The feasibility of cell expansion after initial differentiation was illustrated by homogenous matrix deposition in pellets from twicepassaged GFP+ cells. Finally, atomic force microscopy analysis showed increased microscale elastic moduli associated with collagen alignment at the periphery of pellets, mimicking zonal variation in native cartilage. This study demonstrates the potential use of iPSCs for cartilage defect repair and for creating tissue models of cartilage that can be matched to specific genetic backgrounds.chondrocyte | bone morphogenetic proteins | transforming growth factor-beta | cartilage micromechanics | cartilage regeneration

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Mesenchymal stromal cells derived from whole human umbilical cord exhibit similar properties to those derived from Wharton's jelly and bone marrow

et al. 2016

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Mesenchymal stromal cells (MSC) can be isolated from several regions of human umbilical cords, including Wharton's jelly (WJ), artery, vein or cord lining. These MSC appear to be immune privileged and are promising candidates for cell therapy. However, isolating MSC from WJ, artery, vein or cord lining requires time‐consuming tissue dissection. MSC can be obtained easily via briefly digesting complete segments of the umbilical cord, likely containing heterogenous or mixed populations of MSC (MC‐MSC). MC‐MSC are generally less well characterized than WJ‐MSC, but nevertheless represent a potentially valuable population of MSC. This study aimed to further characterize MC‐MSC in comparison to WJ‐MSC and also the better‐characterized bone marrow‐derived MSC (BM‐MSC). MC‐MSC proliferated faster, with significantly faster doubling times reaching passage one 8.8 days sooner and surviving longer in culture than WJ‐MSC. All MSC retained the safety aspect of reducing telomere length with increasing passage number. MSC were also assessed for their ability to suppress T‐cell proliferation and for the production of key markers of pluripotency, embryonic stem cells, tolerogenicity (CD40, CD80, CD86 and HLA‐DR) and immunomodulation (indoleamine 2,3‐dioxygenase [IDO] and HLA‐G). The MC‐MSC population displayed all of the positive attributes of WJ‐MSC and BM‐MSC, but they were more efficient to obtain and underwent more population doublings than from WJ, suggesting that MC‐MSC are promising candidates for allogeneic cell therapy in regenerative medicine.

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Fibroblast Growth Factor-2 Enhances Proliferation and Delays Loss of Chondrogenic Potential in Human Adult Bone-Marrow-Derived Mesenchymal Stem Cells

Cited by 175 publications

References 52 publications

Expansion in the presence of FGF-2 enhances the functional development of cartilaginous tissues engineered using infrapatellar fat pad derived MSCs

Expansion in the presence of FGF-2 enhances the functional development of cartilaginous tissues engineered using infrapatellar fat pad derived MSCs

Cartilage tissue engineering using differentiated and purified induced pluripotent stem cells

Mesenchymal stromal cells derived from whole human umbilical cord exhibit similar properties to those derived from Wharton's jelly and bone marrow

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