Mesenchymal Cell News Volume 5.25 | Jul 2 2013

Inhibition of Rac1 Promotes BMP-2-Induced Osteoblastic Differentiation
A previous study has demonstrated that the Ras homolog family-associated protein kinase (ROCK) inhibitor Y-27632 enhanced bone formation induced by recombinant human bone morphogenetic protein-2 (BMP-2) in vivo and in vitro. However, the effect of other Rho family members, such as Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division cycle 42, on bone formation remains unknown. In this study, scientists investigated whether Rac1 also participates in BMP-2-induced osteogenesis. Expression of a dominant-negative mutant of Rac1 enhanced BMP-2-induced osteoblastic differentiation in C2C12 cells, whereas a constitutively active mutant of Rac1 attenuated that effect. [Cell Death Dis] Full Article

GAPDH Is Critical for Superior Efficacy of Female Bone Marrow-Derived Mesenchymal Stem Cells on Pulmonary Hypertension
Researchers aimed to add new insight in gender differences of bone marrow-derived mesenchymal stem cells on therapy against pulmonary arterial hypertension and the underlying mechanism. In vitro experiments demonstrated superior function of female bone marrow-derived mesenchymal stem cells in cell proliferation, migration and [Ca²⁺]_i kinetics. [Cardiovasc Res] Abstract

HIV Protease Inhibitors Induce Senescence and Alter Osteoblastic Potential of Human Bone Marrow Mesenchymal Stem Cells: Beneficial Effect of Pravastatin
In endothelial cells, some protease inhibitors (PIs) have been shown to induce the accumulation of farnesylated-prelamin-A, a biomarker of cell aging leading to cell senescence. Investigators hypothesized that these PIs could induce premature aging of osteoblast precursors, human bone marrow mesenchymal stem cells, and affect their capacity to differentiate into osteoblasts. [Aging Cell] Abstract

The Winged Helix Transcription Factor Foxa3 Regulates Adipocyte Differentiation and Depot-Selective Fat Tissue Expansion
The authors performed a siRNA screen of Forkhead-box genes in adipocytes and showed for the first time that the winged helix factor Foxa3 promotes adipocyte differentiation by cooperating with C/EBPß and d to transcriptionally induce PPAR? expression. [Mol Cell Biol] Abstract

Interleukin-6 Downregulation with Mesenchymal Stem Cell Differentiation Results in Loss of Immunoprivilege
Scientists investigated the influence of interleukin-6 (IL-6), a factor secreted by mesenchymal stem cell (MSC), on immune privilege after myogenic, endothelial and smooth muscle cell differentiation induced by 5-azacytidine, VEGF, and transforming growth factor-ß, respectively. Both RT-PCR and ELISA showed that myogenic differentiation of MSCs was associated with significant downregulation of IL-6 expression, which was also observed following endothelial and smooth muscle cell differentiation, indicating that IL-6 downregulation was dependent on differentiation but not cell phenotype. [J Cell Mol Med] Full Article

Prospective Purification of a Subpopulation of Human Synovial Mesenchymal Stem Cells with Enhanced Chondro-Osteogenic Potency
Scientists investigated marker sets for prospective purification of functionally distinct mesenchymal stem cell subsets. During culture expansion, the co-localization of CD39 within the CD73⁺ cell population identified a small cell subset that was maintained from passage 1 (P1) up to at least P12 in all donors tested. [Rheumatology] Abstract

Bone-Derived Mesenchymal Stromal Cells from HIV Transgenic Mice Exhibit Altered Proliferation, Differentiation Capacity and Paracrine Functions Along with Impaired Therapeutic Potential in Kidney Injury
Researchers evaluated cellular proliferation, differentiation and paracrine functions of mesenchymal stem cells (MSCs) isolated from compact bones of healthy control mice and Tg26 HIV-1 transgenic mice. They successfully isolated MSCs from healthy mice and Tg26 HIV-1 transgenic mice and found the latter expressed viral Nef, Vpu, NL4-3 and Vif genes. [Exp Cell Res] Abstract

Adipose-Derived Stem Cells Combined with Inorganic Bovine Bone in Calvarial Bone Healing in Type 2 Diabetic Rats
Scientists sought to investigate whether adipose-derived stem cells combined with inorganic bovine bone improve bone repair in calvarial vertical critical-sized defects in type 2 diabetic rats. The histological results showed an increase in new bone formation in the experimental groups compared with the control group. [J Periodontol] Abstract

New Methods for Inducing the Differentiation of Amniotic-Derived Mesenchymal Stem Cells into Motor Neuron Precursor Cells
Researchers investigated the differentiation of amniotic-derived mesenchymal stem cells into motor neuron precursor cells induced by a combination of extracellular matrix and multi-cell factors. [Tissue Cell] Abstract

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Mesoblast Receives Clearance to Begin Phase II Clinical Trial of Mesenchymal Precursor Cells in Diabetic Nephropathy
Mesoblast Limited announced that it has received approvals from Australian ethics committees to commence a Phase II trial evaluating a single intravenous infusion of its proprietary allogeneic or “off-the-shelf” adult Mesenchymal Precursor Cells in patients with type 2 diabetes and advanced kidney disease, or diabetic nephropathy. [Mesoblast Limited] Press Release

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NEW Two PhD Students and One Postdoc – Molecular Cell Biology and Hematopoiesis (Sanquin)

NEW PhD Positions – Tissue Engineering (Eight European Research Institutes)

Postdoctoral Fellow – Visualization of Gene Expression Promoting Mesenchymal Stem Cell Tropism (Johns Hopkins University School of Medicine)

Postdoctoral Researcher – Basic and Translational Hemato-Oncology (Josep Carreras Leukaemia Research Institute (IJC))

Director of Cell Processing Facility (S L Collins Associates, Inc.)

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