Inhibition of osteoblast differentiation but not adipocyte differentiation of mesenchymal stem cells by sera obtained from aged females

Abdallah, Basem M.; Haack‐Sørensen, Mandana; Fink, Trine; Kassem, Moustapha

doi:10.1016/j.bone.2005.12.082

Cited by 125 publications

(107 citation statements)

References 28 publications

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“…Staining for alkaline phosphatase (ALP): Cells undergoing osteoblast differentiation for 10, 15, and 21 days were stained for ALP as described previously (36) using incubation in an ALP substrate solution containing naphthol AS-TR phosphate (0.2 mg/mL in water) mixed with fast red TR (0.417 mg/mL in 0.1 M Tris buffer, pH 9.5) for 1 hour at room temperature.…”

Section: Cytochemical Stainingmentioning

confidence: 99%

“…(36) Oil red-O staining for lipids: Cells were induced to adipocyte differentiation as described earlier. Lipid-filled adipocytes were visualized using oil red-O staining solution (prepared by dissolving 0.5 g oil red-O powder in 60% isopropanol) and counterstained with Mayer's hematoxylin.…”

Section: Cytochemical Stainingmentioning

confidence: 99%

“…We then induced the cells to differentiate into adipocytes using our previously reported adipocyte induction mixture (AIM) (36) for 15 days. Gene expression analysis revealed significant upregulation of adipogenic gene marker expression: adipocyte fatty-acidbinding protein (aP2), lipoprotein lipase (LPL), and nuclear factor peroxisome proliferator-activated receptor g (PPARg2) (Fig.…”

Section: Differentiation Of Sb-og Cells Into Mesenchymal Progenitorsmentioning

confidence: 99%

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Enhanced differentiation of human embryonic stem cells to mesenchymal progenitors by inhibition of TGF-β/activin/nodal signaling using SB-431542

Mahmood

Harkness²,

Schrøder

et al. 2010

Journal of Bone and Mineral Research

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112

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Directing differentiation of human embryonic stem cells (hESCs) into specific cell types using an easy and reproducible protocol is a prerequisite for the clinical use of hESCs in regenerative-medicine procedures. Here, we report a protocol for directing the differentiation of hESCs into mesenchymal progenitor cells. We demonstrate that inhibition of transforming growth factor b (TGF-b)/activin/nodal signaling during embryoid body (EB) formation using SB-431542 (SB) in serum-free medium markedly upregulated paraxial mesodermal markers (TBX6, TBX5) and several myogenic developmental markers, including early myogenic transcriptional factors (Myf5, Pax7), as well as myocyte-committed markers [NCAM, CD34, desmin, MHC (fast), a-smooth muscle actin, Nkx2.5, cTNT]. Continuous inhibition of TGF-b signaling in EB outgrowth cultures (SB-OG) enriched for myocyte progenitor cells; markers were PAX7 þ (25%), MYOD1 þ (52%), and NCAM þ (CD56) (73%). DNA microarray analysis revealed differential upregulation of 117 genes (>2-fold compared with control cells) annotated to myogenic development and function. Moreover, these cells showed the ability to contract (80% of the population) and formed myofibers when implanted intramuscularly in vivo. Interestingly, SB-OG cells cultured in 10% fetal bovine serum (FBS) developed into a homogeneous population of mesenchymal progenitors that expressed CD markers characteristic of mesenchymal stem cells (MSCs): CD44 þ (100%), CD73 þ (98%), CD146 þ (96%), and CD166 þ (88%) with the ability to differentiate into osteoblasts, adipocytes, and chondrocytes in vitro and in vivo. Furthermore, microarray analysis of these cells revealed downregulation of genes related to myogenesis: MYH3 (À167.9-fold), ACTA1 (À161-fold), MYBPH (À139-fold), ACTC (À100.3-fold), MYH8 (À45.5-fold), and MYOT (À41.8-fold) and marked upregulation of genes related to mesoderm-derived cell lineages. In conclusion, our data provides a simple and versatile protocol for directing the differentiation of hESCs into a myogenic lineage and then further into mesenchymal progenitors by blocking the TGF-b signaling pathway. ß

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Section: Cytochemical Stainingmentioning

confidence: 99%

Section: Cytochemical Stainingmentioning

confidence: 99%

Section: Differentiation Of Sb-og Cells Into Mesenchymal Progenitorsmentioning

confidence: 99%

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Enhanced differentiation of human embryonic stem cells to mesenchymal progenitors by inhibition of TGF-β/activin/nodal signaling using SB-431542

Mahmood

Harkness²,

Schrøder

et al. 2010

Journal of Bone and Mineral Research

Self Cite

112

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“…Another alternative to fetal calf serum is autologous patient serum. However, it appears to be less favorable, since serum derived from aged individuals interferes with MSC proliferation and/or differentiation capacity (Abdallah et al, 2006;Mannello and Tonti, 2007).…”

Section: Msc and Serum-containing Culture Mediamentioning

confidence: 99%

Controversial issue: Is it safe to employ mesenchymal stem cells in cell-based therapies?

Lepperdinger

Brunauer

Jamnig

et al. 2008

Experimental Gerontology

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113

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“…(3) Several possible cellular and molecular mechanisms can mediate the defective osteoblastic functions, including cell-autonomous intrinsic defects (4) and defective microenvironment owing to age-related changes in the humoral milieu in bone microenvironment. (5) One of the principal mechanisms responsible for age-related defective cellular functions, known collectively as cellular senescence, is telomere shortening caused by incomplete replication of linear chromosomes by DNA polymerase.…”

Section: Introductionmentioning

confidence: 99%

Telomerase-deficient mice exhibit bone loss owing to defects in osteoblasts and increased osteoclastogenesis by inflammatory microenvironment

Saeed

Abdallah

Ditzel

et al. 2011

Journal of Bone and Mineral Research

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Telomere shortening owing to telomerase deficiency leads to accelerated senescence of human skeletal (mesenchymal) stem cells (MSCs) in vitro, whereas overexpression leads to telomere elongation, extended life span, and enhanced bone formation. To study the role of telomere shortening in vivo, we studied the phenotype of telomerase-deficient mice (Terc À/À ). Terc À/À mice exhibited accelerated age-related bone loss starting at 3 months of age and during 12 months of follow-up revealed by dual-energy X-ray absorptiometric (DXA) scanning and by micro-computed tomography (mCT). Bone histomorphometry revealed decreased mineralized surface and boneformation rate as well as increased osteoclast number and size in Terc À/À mice. Also, serum total deoxypyridinoline (tDPD) was increased

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Inhibition of osteoblast differentiation but not adipocyte differentiation of mesenchymal stem cells by sera obtained from aged females

Cited by 125 publications

References 28 publications

Enhanced differentiation of human embryonic stem cells to mesenchymal progenitors by inhibition of TGF-β/activin/nodal signaling using SB-431542

Enhanced differentiation of human embryonic stem cells to mesenchymal progenitors by inhibition of TGF-β/activin/nodal signaling using SB-431542

Controversial issue: Is it safe to employ mesenchymal stem cells in cell-based therapies?

Telomerase-deficient mice exhibit bone loss owing to defects in osteoblasts and increased osteoclastogenesis by inflammatory microenvironment

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