Chip-Based Comparison of the Osteogenesis of Human Bone Marrow- and Adipose Tissue-Derived Mesenchymal Stem Cells under Mechanical Stimulation

Adipose tissue-derived stem cells (ASCs) are considered as an attractive stem cell source for tissue engineering and regenerative medicine. We compared human bone marrow-derived mesenchymal stem cells (hMSCs) and hASCs under dynamic hydraulic compression to evaluate and compare osteogenic abilities. A novel micro cell chip integrated with microvalves and microscale cell culture chambers separated from an air-pressure chamber was developed using microfabrication technology. The microscale chip enables the culture of two types of stem cells concurrently, where each is loaded into cell culture chambers and dynamic compressive stimulation is applied to the cells uniformly. Dynamic hydraulic compression (1 Hz, 1 psi) increased the production of osteogenic matrix components (bone sialoprotein, oateopontin, type I collagen) and integrin (CD11b and CD31) expression from both stem cell sources. Alkaline phosphatase and Alrizarin red staining were evident in the stimulated hMSCs, while the stimulated hASCs did not show significant increases in staining under the same stimulation conditions. Upon application of mechanical stimulus to the two types of stem cells, integrin (β1) and osteogenic gene markers were upregulated from both cell types. In conclusion, stimulated hMSCs and hASCs showed increased osteogenic gene expression compared to non-stimulated groups. The hMSCs were more sensitive to mechanical stimulation and more effective towards osteogenic differentiation than the hASCs under these modes of mechanical stimulation.

[1]  P. Rambaut,et al.  SKELETAL CHANGES DURING SPACE FLIGHT , 1985, The Lancet.

[2]  J. Tschopp,et al.  Design and synthesis of novel cyclic RGD-containing peptides as highly potent and selective integrin alpha IIb beta 3 antagonists. , 1994, Journal of medicinal chemistry.

[3]  R. Carvalho,et al.  The effects of mechanical stimulation on the distribution of beta 1 integrin and expression of beta 1-integrin mRNA in TE-85 human osteosarcoma cells. , 1995, Archives of oral biology.

[4]  R. Carvalho,et al.  The effects of mechanical stimulation on the distribution of β1 integrin and expression of β1-integrin mRNA in TE-85 human osteosarcoma cells , 1995 .

[5]  C. Damsky,et al.  Integrin-extracellular matrix interactions in connective tissue remodeling and osteoblast differentiation. , 1995, ASGSB bulletin : publication of the American Society for Gravitational and Space Biology.

[6]  H. Petty,et al.  Beta 2 (CD11/CD18) integrins can serve as signaling partners for other leukocyte receptors. , 1997, The Journal of laboratory and clinical medicine.

[7]  G. Karsenty,et al.  Osf2/Cbfa1: A Transcriptional Activator of Osteoblast Differentiation , 1997, Cell.

[8]  J. Davies,et al.  Biochemical analysis of the response in rat bone marrow cell cultures to mechanical stimulation. , 1997, Bio-medical materials and engineering.

[9]  Makoto Sato,et al.  Targeted Disruption of Cbfa1 Results in a Complete Lack of Bone Formation owing to Maturational Arrest of Osteoblasts , 1997, Cell.

[10]  B. Nebe,et al.  Mechanical Stressing of Integrin Receptors Induces Enhanced Tyrosine Phosphorylation of Cytoskeletally Anchored Proteins* , 1998, The Journal of Biological Chemistry.

[11]  M. Pittenger,et al.  Multilineage potential of adult human mesenchymal stem cells. , 1999, Science.

[12]  E. Hébert.  Endogenous Lectins as Cell Surface Transducers , 2000, Bioscience reports.

[13]  C. Carron,et al.  Mechanically strained cells of the osteoblast lineage organize their extracellular matrix through unique sites of alphavbeta3-integrin expression. , 2000, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[14]  C. Carron,et al.  Mechanically Strained Cells of the Osteoblast Lineage Organize Their Extracellular Matrix Through Unique Sites of αVβ3‐Integrin Expression , 2000 .

[15]  D Kaspar,et al.  Dynamic cell stretching increases human osteoblast proliferation and CICP synthesis but decreases osteocalcin synthesis and alkaline phosphatase activity. , 2000, Journal of biomechanics.

[16]  H. Lorenz,et al.  Multilineage cells from human adipose tissue: implications for cell-based therapies. , 2001, Tissue engineering.

[17]  K. Arihiro,et al.  Expression of CD31, Met/hepatocyte growth factor receptor and bone morphogenetic protein in bone metastasis of osteosarcoma , 2001, Pathology international.

[18]  Min Zhu,et al.  Human adipose tissue is a source of multipotent stem cells. , 2002, Molecular biology of the cell.

[19]  J. Penninger,et al.  The role of LFA-1 in osteoclast development induced by co-cultures of mouse bone marrow cells and MC3T3-G2/PA6 cells. , 2002, Journal of periodontal research.

[20]  B. Nebe,et al.  The Mode of Mechanical Integrin Stressing Controls Intracellular Signaling in Osteoblasts , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[21]  Antonios G. Mikos,et al.  Fluid flow increases mineralized matrix deposition in 3D perfusion culture of marrow stromal osteoblasts in a dose-dependent manner , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[22]  K. Lau,et al.  Fluid flow shear stress stimulates human osteoblast proliferation and differentiation through multiple interacting and competing signal transduction pathways. , 2003, Bone.

[23]  Li Zhang,et al.  Modulation of CD11b/CD18 Adhesive Activity by Its Extracellular, Membrane-Proximal Regions1 , 2003, The Journal of Immunology.

[24]  N. Ilan,et al.  PECAM-1: old friend, new partners. , 2003, Current opinion in cell biology.

[25]  J. Aubin,et al.  Global amplification polymerase chain reaction reveals novel transitional stages during osteoprogenitor differentiation , 2003, Journal of Cell Science.

[26]  Min Zhu,et al.  Comparison of Multi-Lineage Cells from Human Adipose Tissue and Bone Marrow , 2003, Cells Tissues Organs.

[27]  Michael Kjaer,et al.  Role of extracellular matrix in adaptation of tendon and skeletal muscle to mechanical loading. , 2004, Physiological reviews.

[28]  C Krettek,et al.  Effects of cyclic longitudinal mechanical strain and dexamethasone on osteogenic differentiation of human bone marrow stromal cells. , 2004, European cells & materials.

[29]  Ung-Jin Kim,et al.  Three-dimensional aqueous-derived biomaterial scaffolds from silk fibroin. , 2005, Biomaterials.

[30]  Li Zhang,et al.  Defective osteogenesis of the stromal stem cells predisposes CD18-null mice to osteoporosis. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[31]  D. Benayahu,et al.  Characterization of adhesion and differentiation markers of osteogenic marrow stromal cells , 2005, Journal of cellular physiology.

[32]  L. Natarajan,et al.  Quantifying Estrogen and Progesterone Receptor Expression in Breast Cancer by Digital Imaging , 2005, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[33]  M. Hoshino,et al.  Bone Marrow Stromal Cells Generate Muscle Cells and Repair Muscle Degeneration , 2005, Science.

[34]  Ung-Jin Kim,et al.  Influence of macroporous protein scaffolds on bone tissue engineering from bone marrow stem cells. , 2005, Biomaterials.

[35]  Subburaman Mohan,et al.  Global gene expression analysis in the bones reveals involvement of several novel genes and pathways in mediating an anabolic response of mechanical loading in mice , 2005, Journal of cellular biochemistry.

[36]  Jenneke Klein-Nulend,et al.  Adipose tissue-derived mesenchymal stem cells acquire bone cell-like responsiveness to fluid shear stress on osteogenic stimulation. , 2005, Tissue engineering.

[37]  R. Ogawa.  The importance of adipose-derived stem cells and vascularized tissue regeneration in the field of tissue transplantation. , 2006, Current stem cell research & therapy.

[38]  D. Rimm,et al.  Immunohistochemistry and quantitative analysis of protein expression. , 2009, Archives of pathology & laboratory medicine.

[39]  A. Khademhosseini,et al.  Microscale technologies for tissue engineering and biology. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[40]  Sang-Hyug Park,et al.  An electromagnetic compressive force by cell exciter stimulates chondrogenic differentiation of bone marrow-derived mesenchymal stem cells. , 2006, Tissue engineering.

[41]  J. Rubin,et al.  Response to mechanical strain in an immortalized pre‐osteoblast cell is dependent on ERK1/2 , 2006, Journal of cellular physiology.

[42]  Woo Young Sim,et al.  A pneumatic micro cell chip for the differentiation of human mesenchymal stem cells under mechanical stimulation. , 2007, Lab on a chip.

[43]  Ariel Simkin,et al.  Increased trabecular bone density due to bone-loading exercises in postmenopausal osteoporotic women , 1987, Calcified Tissue International.

[44]  P. Agius,et al.  Mechanical strain enhances extracellular matrix-induced gene focusing and promotes osteogenic differentiation of human mesenchymal stem cells through an extracellular-related kinase-dependent pathway. , 2007, Stem cells and development.

[45]  Li-chi Han,et al.  Mechanical strain induces osteogenic differentiation: Cbfa1 and Ets-1 expression in stretched rat mesenchymal stem cells. , 2008, International journal of oral and maxillofacial surgery.

[46]  Z. Cui,et al.  Adipose-derived stem cell: A better stem cell than BMSC , 2008, Cell Research.

[47]  Takehiko Kitamori,et al.  Development of an osteoblast-based 3D continuous-perfusion microfluidic system for drug screening , 2008, Analytical and bioanalytical chemistry.

[48]  Hajime Ohgushi,et al.  Comparison of Osteogenic Ability of Rat Mesenchymal Stem Cells from Bone Marrow, Periosteum, and Adipose Tissue , 2008, Calcified Tissue International.

[49]  Shyni Varghese,et al.  Controlled differentiation of stem cells. , 2008, Advanced drug delivery reviews.

[50]  C. Haasper,et al.  Influence of perfusion and cyclic compression on proliferation and differentiation of bone marrow stromal cells in 3-dimensional culture. , 2008, Journal of biomechanics.

[51]  Christopher S. Chen,et al.  Emergence of Patterned Stem Cell Differentiation Within Multicellular Structures , 2008, Stem cells.

[52]  Li-chi Han,et al.  Expression of Bone-related Genes in Bone Marrow MSCs after Cyclic Mechanical Strain: Implications for Distraction Osteogenesis , 2009, International Journal of Oral Science.

[53]  Skylar W. Marvel,et al.  Osteogenic Effects of Rest Inserted and Continuous Cyclic Tensile Strain on hASC Lines with Disparate Osteodifferentiation Capabilities , 2009, Annals of Biomedical Engineering.

[54]  D. Ingber,et al.  Reconstituting Organ-Level Lung Functions on a Chip , 2010, Science.

[55]  Regina Luttge,et al.  The interaction between nanoscale surface features and mechanical loading and its effect on osteoblast-like cells behavior. , 2010, Biomaterials.

[56]  Kangil Kim,et al.  The optimization of PDMS-PMMA bonding process using silane primer , 2010 .

[57]  Ali Khademhosseini,et al.  Benchtop fabrication of PDMS microstructures by an unconventional photolithographic method , 2010, Biofabrication.

[58]  Shmuel Einav,et al.  The effect of mechanical loads in the differentiation of precursor cells into mature cells , 2010, Annals of the New York Academy of Sciences.

[59]  Yu Sun,et al.  A microfabricated platform for high-throughput unconfined compression of micropatterned biomaterial arrays. , 2010, Biomaterials.

[60]  Monya Baker,et al.  Tissue models: A living system on a chip , 2011, Nature.

[61]  M. Hoshino,et al.  Mari Dezawa Degeneration Bone Marrow Stromal Cells Generate Muscle Cells and Repair Muscle , 2013 .