The Response of Human Mesenchymal Stem Cells to Osteogenic Signals and its Impact on Bone Tissue Engineering

Siddappa, Ramakrishnaiah; Fernandes, Hugo; Liu, Jun; Blitterswijk, Clemens A. van; Boer, Jan de

doi:10.2174/157488807781696267

Cited by 63 publications

(49 citation statements)

References 124 publications

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“…In previous studies, dexamethasone (dex) and vitamin D3 were used to promote hMSC differentiation in vitro (12). More recent studies include the MAPK pathway (13), Rho kinase (7), Wnt (5), Notch (14), and receptor tyrosine kinases (3).…”

mentioning

confidence: 99%

cAMP/PKA pathway activation in human mesenchymal stem cells in vitro results in robust bone formation in vivo

Siddappa

Martens

Doorn

et al. 2008

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

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Tissue engineering of large bone defects is approached through implantation of autologous osteogenic cells, generally referred to as multipotent stromal cells or mesenchymal stem cells (MSCs). Animal-derived MSCs successfully bridge large bone defects, but models for ectopic bone formation as well as recent clinical trials demonstrate that bone formation by human MSCs (hMSCs) is inadequate. The expansion phase presents an attractive window to direct hMSCs by pharmacological manipulation, even though no profound effect on bone formation in vivo has been described so far using this approach. We report that activation of protein kinase A elicits an immediate response through induction of genes such as ID2 and FosB, followed by sustained secretion of bone-related cytokines such as BMP-2, IGF-1, and IL-11. As a consequence, PKA activation results in robust in vivo bone formation by hMSCs derived from orthopedic patients.bone tissue engineering ͉ osteogenesis ͉ PKA signaling

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mentioning

confidence: 99%

cAMP/PKA pathway activation in human mesenchymal stem cells in vitro results in robust bone formation in vivo

Siddappa

Martens

Doorn

et al. 2008

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

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205

149

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“…Several studies are reported for differentiation of MSCs in-vitro and in-vivo. Reports indicating differentiation of MSCs in vitro in dexamethasone enriched media have been concluded Differentiation into osteo-cell lines and hence participation in bone formation (Bruder et al 1997(Bruder et al , 1998Siddappa et al 2007). Studies suggesting possibilities of MSCs playing pivotal role in regeneration of vascular tissues are said to play a key role in associated therapies such as impotence, disseminated sclerosis and conditions associated with spinal cord injury (Albersen et al 2011;Steffenhagen et al 2011).…”

Section: Introductionmentioning

confidence: 99%

PROTECTIVE EFFECT OF Ailanthus excelsa ROXB IN MYOCARDIAL INFARCTION POST MESENCHYMAL STEM CELL TRANSPLANTATION: STUDY IN CHRONIC ISCHEMIC RAT MODEL

Gong¹

2016

Afr J Tradit Complement Altern Med

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Background: Thia study evaluates the effects of Ailanthus excelsa Roxb methanolic extract (AER-ME) in rats induced with Myocardial Infarction (MI) followed by transplantation of MSCs. Material and Methods: Rats were induced with MI by ligation technique of left coronary artery. The sham-operated the control and AER-ME treated group of rats received transplantation of PKH-26 and marked MSCs followed by normal saline and AER-ME treatment (200mg/kg/day of AER-ME extract) respectively for 30 days. Parameters such as cardiac function, inflammation, oxidative stress, apoptosis and differentiation of MSCs (angiogenesis) were evaluated. Histological studies of infracted myocardium reveled antiinflammatory activity of AER-ME treatment. Result and Discussion: Oxidative stress parameters revealed decrease in levels of malondialdehyde (MDA) and increase in superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSHpx) activity significantly indicating antioxidant activity of the extract. There was a reduction in cell death rate of treated rats due to the decrease in apoptotic index with prolongation of MI when compared to both control and sham-operated groups. The expression of Fas protein was parallel to apoptotic index. The vascular density increased significantly in extract treated group. The treatment showed improved cardiac activity with decreased left ventricular end diastolic (LVEDP) and arterial pressure while the left ventricular end systolic pressure (LVEP) and dp/dtmax increased significantly when compared to both control and sham-operated groups respectively showing the protective effect of the extract as necessitated by the transplantation of MSCs. The study marked the protective outcomes of AER-ME treatment for MSCs in microenvironment of infracted myocardium by improving their viability and increasing differentiation into cardiomyocytes.

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“…This kinase will phosphorylate members of the Smad (mothers against decapentaplegic) family of transcription factors which will translocate into the nucleus to activate BMP target genes. This pathway is designated the canonical BMP signalling pathway [Ducy and Karsenty, 2000;Schmierer and Hill, 2007;Siddappa et al, 2007].…”

Section: Introductionmentioning

confidence: 99%

Effect of Chordin-Like 1 on MC3T3-E1 and Human Mesenchymal Stem Cells

Fernandes

Dechering²,

Someren

et al. 2010

Cells Tissues Organs

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Since the discovery that bone morphogenetic proteins (BMPs) are able to induce ectopic bone formation, considerable effort has been devoted to apply it for bone regeneration. BMP activity needs to be temporally and spatially controlled and the organism has devised ways to achieve it. Here we show that the BMP inhibitor chordin-like 1 can interfere with BMP2 signalling thereby affecting the osteogenic differentiation of MC3T3-E1 cells. Besides its function as a BMP antagonist, chordin-like 1 enhanced the proliferation of human mesenchymal stem cells (hMSCs) in a BMP2-independent manner. When MC3T3-E1 cells were exposed to recombinant chordin-like 1 there was an inhibition of alkaline phosphatase (ALP) expression, whereas in the case of hMSCs no effect was observed. However, chordin-like 1 dose-dependently increased the proliferation of hMSCs. This effect is probably BMP2 independent because the chordin-like 1 concentration that stimulates proliferation does not interfere with BMP signalling monitored by a Smad-dependent reporter gene. Our data point towards a novel, BMP-independent role of chordin-like 1 in hMSC proliferation.

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The Response of Human Mesenchymal Stem Cells to Osteogenic Signals and its Impact on Bone Tissue Engineering

Cited by 63 publications

References 124 publications

cAMP/PKA pathway activation in human mesenchymal stem cells in vitro results in robust bone formation in vivo

cAMP/PKA pathway activation in human mesenchymal stem cells in vitro results in robust bone formation in vivo

PROTECTIVE EFFECT OF Ailanthus excelsa ROXB IN MYOCARDIAL INFARCTION POST MESENCHYMAL STEM CELL TRANSPLANTATION: STUDY IN CHRONIC ISCHEMIC RAT MODEL

Effect of Chordin-Like 1 on MC3T3-E1 and Human Mesenchymal Stem Cells

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