Controlling mesenchymal stem cell differentiation by TGFβ family members

Roelen, Bernard A.J.; Dijke, Peter ten

doi:10.1007/s00776-003-0702-2

Cited by 156 publications

(105 citation statements)

References 74 publications

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“…Members of the TGF-β family have also been implicated in directing decisions regarding the fate of MSCs [97]. BMPs induce differentiation of mesenchymal cells into cells with chondroblast or osteoblast phenotypes in vitro.…”

Section: Mesenchymal Stem Cells (Mscs)mentioning

confidence: 99%

Roles of TGF-β family signaling in stem cell renewal and differentiation

2008

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Section: Mesenchymal Stem Cells (Mscs)mentioning

confidence: 99%

Roles of TGF-β family signaling in stem cell renewal and differentiation

2008

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“…Basic FGF was demonstrated to increase proliferation rate and life span in rabbit, dog and human MSC while maintaining their potential to differentiate towards fat, cartilage and bone [133,134]. The family of BMPs has a pivotal role in prechondrogenic condensations and the transition of chondroprogenitor cells into chondrocytes [135][136][137]. Specifically, BMP-2 is expressed in the condensing mesenchyme of the developing limb [138], and regulates chondrogenic development of mesenchymal progenitors [139][140][141].…”

Section: Vivomentioning

confidence: 99%

Cartilage tissue engineering for degenerative joint disease☆

Nešić

Whiteside

Brittberg

et al. 2006

Advanced Drug Delivery Reviews

210

156

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Pain in the joint is often due to cartilage degeneration and represents a serious medical problem affecting people of all ages. Although many, mostly surgical techniques, are currently employed to treat cartilage lesions, none has given satisfactory results in the long term. Recent advances in biology and material science have brought tissue engineering to the forefront of new cartilage repair techniques. The combination of autologous cells, specifically designed scaffolds, bioreactors, mechanical stimulations and growth factors together with the knowledge that underlies the principles of cell biology offers promising avenues for cartilage tissue regeneration. The present review explores basic biology mechanisms for cartilage reconstruction and summarizes the advances in the tissue engineering approaches. Furthermore, the limits of the new methods and their potential application in the osteoarthritic conditions are discussed.

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“…The transforming growth factor (TGF-b) signaling through SMAD-2/3 downstream effectors has an increasing interest in regenerative medicine and lineage specification during human embryonic development [15,16]. In contrast to specific bone morphogenic proteins (BMPs), which are known to play an important role in directing cell fate decisions toward mesoderm and further differentiation into MSCs, the mesodermal effects of TGF-b signaling in human embryonic development is controversial [15,16].…”

Section: Introductionmentioning

confidence: 99%

“…In contrast to specific bone morphogenic proteins (BMPs), which are known to play an important role in directing cell fate decisions toward mesoderm and further differentiation into MSCs, the mesodermal effects of TGF-b signaling in human embryonic development is controversial [15,16]. We previously reported that specific inhibition of TGF-b signals through SMAD-2/3 results in loss of the hESC phenotype and pluripotency through induction of hESC differentiation, while not affecting survival or selfrenewal of hESCs [17].…”

Section: Introductionmentioning

confidence: 99%

Enrichment of Human ESC-Derived Multipotent Mesenchymal Stem Cells with Immunosuppressive and Anti-Inflammatory Properties Capable to Protect Against Experimental Inflammatory Bowel Disease

Sánchez¹,

Gutiérrez-Aranda²,

Ligero³

et al. 2011

Stem Cells

127

118

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Human ESCs provide access to the earliest stages of human development and may serve as an unlimited source of functional cells for future cell therapies. The optimization of methods directing the differentiation of human embryonic stem cells (hESCs) into tissue-specific precursors becomes crucial. We report an efficient enrichment of mesenchymal stem cells (MSCs) from hESCs through specific inhibition of SMAD-2/3 signaling. Human ESC-derived MSCs (hESC-MSCs) emerged as a population of fibroblastoid cells expressing a MSC phenotype: CD73+ CD90+ CD105+ CD44+ CD166+ CD45− CD34− CD14− CD19− human leucocyte antigen-DR (HLA-DR)−. After 28 days of SMAD-2/3 inhibition, hESC cultures were enriched (>42%) in multipotent MSCs. CD73+CD90+ hESC-MSCs were fluorescence activated cell sorting (FACS)-isolated and long-term cultures were established and maintained for many passages displaying a faster growth than somatic tissue-derived MSCs while maintaining MSC morphology and phenotype. They displayed osteogenic, adipogenic, and chondrocytic differentiation potential and exhibited potent immunosuppressive and anti-inflammatory properties in vitro and in vivo, where hESC-MSCs were capable of protecting against an experimental model of inflammatory bowel disease. Interestingly, the efficient enrichment of hESCs into MSCs through inhibition of SMAD-2/3 signaling was not reproducible with distinct induced pluripotent stem cell lines. Our findings provide mechanistic insights into the differentiation of hESCs into immunosuppressive and anti-inflammatory multipotent MSCs with potential future clinical applications.

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Controlling mesenchymal stem cell differentiation by TGFβ family members

Cited by 156 publications

References 74 publications

Roles of TGF-β family signaling in stem cell renewal and differentiation

Roles of TGF-β family signaling in stem cell renewal and differentiation

Cartilage tissue engineering for degenerative joint disease☆

Enrichment of Human ESC-Derived Multipotent Mesenchymal Stem Cells with Immunosuppressive and Anti-Inflammatory Properties Capable to Protect Against Experimental Inflammatory Bowel Disease

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