Hypoxia inducible factor-stabilizing bioactive glasses for directing mesenchymal stem cell behavior.

Oxygen tension is a known regulator of mesenchymal stem cell (MSC) plasticity, differentiation, proliferation, and recruitment to sites of injury. Materials capable of affecting the MSC oxygen-sensing pathway, independently of the environmental oxygen pressure, are therefore of immense interest to the tissue engineering (TE) and regenerative medicine community. In this study, we describe the evaluation of the effect of hypoxia inducible factor (HIF)-stabilizing bioactive glasses (BGs) on human MSCs. The dissolution products from these hypoxia-mimicking BGs stabilized HIF-1α in a concentration-dependent manner, altered cell proliferation and metabolism, and upregulated a number of genes involved in the hypoxic response (HIF1A, HIF2A, and VHL), MSC survival (SAG and BCL2), extracellular matrix remodeling (MMP1), and angiogenesis (VEGF and PDGF). These HIF-stabilizing materials can therefore be used to improve MSC survival and enhance regeneration in a number of TE strategies.

[1]  David L. Nelson,et al.  Lehninger Principles of Biochemisty , 2015 .

[2]  A. Caplan,et al.  Mesenchymal Stem Cells in Tissue Repair , 2013, Front. Immunol..

[3]  C. Sen,et al.  Differential roles of hypoxia inducible factor subunits in multipotential stromal cells under hypoxic condition , 2011, Journal of cellular biochemistry.

[4]  Jerome Ritz,et al.  The elusive nature and function of mesenchymal stem cells , 2011, Nature Reviews Molecular Cell Biology.

[5]  W. Xue,et al.  Hypoxic preconditioning advances CXCR4 and CXCR7 expression by activating HIF-1α in MSCs. , 2010, Biochemical and biophysical research communications.

[6]  G. Jell,et al.  Synthesis and characterization of hypoxia-mimicking bioactive glasses for skeletal regeneration , 2010 .

[7]  Gavin Jell,et al.  The effects of strontium-substituted bioactive glasses on osteoblasts and osteoclasts in vitro. , 2010, Biomaterials.

[8]  T. Doyle,et al.  Angiogenic Effects Despite Limited Cell Survival of Bone Marrow-Derived Mesenchymal Stem Cells under Ischemia , 2010, The Thoracic and cardiovascular surgeon.

[9]  Eric Farrell,et al.  The role of hypoxia in bone marrow-derived mesenchymal stem cells: considerations for regenerative medicine approaches. , 2010, Tissue engineering. Part B, Reviews.

[10]  Young-ho Kim.  Mesenchymal stem cells cultured under hypoxia escape from senescence via down-regulation of p16 and extracellular signal regulated kinase , 2010 .

[11]  Ingo Müller,et al.  Low physiologic oxygen tensions reduce proliferation and differentiation of human multipotent mesenchymal stromal cells , 2010, BMC Cell Biology.

[12]  Richard O C Oreffo,et al.  Hypoxia inducible factors regulate pluripotency and proliferation in human embryonic stem cells cultured at reduced oxygen tensions , 2010, Reproduction.

[13]  E. Schipani,et al.  Bone marrow mesenchymal stem cells , 2009, Journal of cellular biochemistry.

[14]  Chao Yang,et al.  Self‐renewal and pluripotency is maintained in human embryonic stem cells by co‐culture with human fetal liver stromal cells expressing hypoxia inducible factor 1α , 2009, Journal of cellular physiology.

[15]  E. Place,et al.  Complexity in biomaterials for tissue engineering. , 2009, Nature materials.

[16]  M. Simon,et al.  The role of oxygen availability in embryonic development and stem cell function , 2008, Nature Reviews Molecular Cell Biology.

[17]  Ling Wei,et al.  Transplantation of hypoxia-preconditioned mesenchymal stem cells improves infarcted heart function via enhanced survival of implanted cells and angiogenesis. , 2008, The Journal of thoracic and cardiovascular surgery.

[18]  K. Shakesheff,et al.  The effect of mesenchymal populations and vascular endothelial growth factor delivered from biodegradable polymer scaffolds on bone formation. , 2008, Biomaterials.

[19]  Regina Brunauer,et al.  Reduced oxygen tension attenuates differentiation capacity of human mesenchymal stem cells and prolongs their lifespan , 2007, Aging cell.

[20]  A. Caplan.  Adult mesenchymal stem cells for tissue engineering versus regenerative medicine , 2007, Journal of cellular physiology.

[21]  G. Semenza,et al.  Life with Oxygen , 2007, Science.

[22]  M. Ashraf,et al.  HIF-1alpha induced-VEGF overexpression in bone marrow stem cells protects cardiomyocytes against ischemia. , 2007, Journal of molecular and cellular cardiology.

[23]  S. Kitamura,et al.  Effect of Hypoxia on Gene Expression of Bone Marrow‐Derived Mesenchymal Stem Cells and Mononuclear Cells , 2007, Stem cells.

[24]  Karim Oudina,et al.  Hypoxia affects mesenchymal stromal cell osteogenic differentiation and angiogenic factor expression. , 2007, Bone.

[25]  V. Eder,et al.  Multipotential Mesenchymal Stem Cells Are Mobilized into Peripheral Blood by Hypoxia , 2006, Stem Cells.

[26]  R. Zhao,et al.  Proliferation and differentiation of bone marrow stromal cells under hypoxic conditions. , 2006, Biochemical and biophysical research communications.

[27]  M. Bernaudin,et al.  Synergistic effects of CoCl2 and ROCK inhibition on mesenchymal stem cell differentiation into neuron-like cells , 2006, Journal of Cell Science.

[28]  G. Semenza,et al.  Expression of Vascular Endothelial Growth Factor Receptor 1 in Bone Marrow-derived Mesenchymal Cells Is Dependent on Hypoxia-inducible Factor 1* , 2006, Journal of Biological Chemistry.

[29]  David J Mooney,et al.  Coating of VEGF-releasing scaffolds with bioactive glass for angiogenesis and bone regeneration. , 2006, Biomaterials.

[30]  M. Bosetti,et al.  The effect of bioactive glasses on bone marrow stromal cells differentiation. , 2005, Biomaterials.

[31]  P. Schiller,et al.  Marrow-isolated adult multilineage inducible (MIAMI) cells, a unique population of postnatal young and old human cells with extensive expansion and differentiation potential , 2004, Journal of Cell Science.

[32]  Julian R. Jones,et al.  Nodule formation and mineralisation of human primary osteoblasts cultured on a porous bioactive glass scaffold. , 2004, Biomaterials.

[33]  M. Burnett,et al.  Marrow-Derived Stromal Cells Express Genes Encoding a Broad Spectrum of Arteriogenic Cytokines and Promote In Vitro and In Vivo Arteriogenesis Through Paracrine Mechanisms , 2004, Circulation research.

[34]  George M. Hilliard,et al.  Cobalt Inhibits the Interaction between Hypoxia-inducible Factor-α and von Hippel-Lindau Protein by Direct Binding to Hypoxia-inducible Factor-α* , 2003, The Journal of Biological Chemistry.

[35]  R. Béliveau,et al.  Hypoxia Promotes Murine Bone‐Marrow‐Derived Stromal Cell Migration and Tube Formation , 2003, Stem cells.

[36]  Larry L Hench,et al.  Third-Generation Biomedical Materials , 2002, Science.

[37]  D. Zukor,et al.  Cytotoxic and apoptotic effects of cobalt and chromium ions on J774 macrophages – Implication of caspase-3 in the apoptotic pathway , 2001, Journal of materials science. Materials in medicine.

[38]  C. Kirkpatrick,et al.  Induction of apoptosis in human microvascular endothelial cells by divalent cobalt ions. Evidence for integrin-mediated signaling via the cytoskeleton , 2001, Journal of materials science. Materials in medicine.

[39]  W M Miller,et al.  Modeling pO(2) distributions in the bone marrow hematopoietic compartment. II. Modified Kroghian models. , 2001, Biophysical journal.

[40]  L L Hench,et al.  Gene-expression profiling of human osteoblasts following treatment with the ionic products of Bioglass 45S5 dissolution. , 2001, Journal of biomedical materials research.

[41]  W. Risau,et al.  Mechanisms of angiogenesis , 1997, Nature.

[42]  G. Semenza,et al.  Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1 , 1996, Molecular and cellular biology.

[43]  Julian R. Jones,et al.  Monodispersed Bioactive Glass Submicron Particles and Their Effect on Bone Marrow and Adipose Tissue‐Derived Stem Cells , 2014, Advanced healthcare materials.

[44]  Julian R Jones,et al.  Review of bioactive glass: from Hench to hybrids. , 2013, Acta biomaterialia.

[45]  Bai Zhifeng,et al.  Angiogenic potency of bone marrow stromal cells improved byex vivo hypoxia prestimulation , 2008, Journal of Huazhong University of Science and Technology [Medical Sciences].

[46]  D. Millhorn,et al.  Cobalt inhibits the interaction between hypoxia-inducible factor-alpha and von Hippel-Lindau protein by direct binding to hypoxia-inducible factor-alpha. , 2003, The Journal of biological chemistry.

[47]  Hypoxia Prestimulation.  Angiogenic Potency of Bone Marrow Stromal Cells Improved by ex Vivo Hypoxia Prestimulation , 2022 .