Presentation on theme: "Mechanical Regulation of Mesenchymal Stem Cell Regulation"— Presentation transcript:
1Mechanical Regulation of Mesenchymal Stem Cell Regulation Tissue EngineeringLecture 10, 3/10/15Paper ReviewMechanical Regulation of Mesenchymal Stem Cell Regulation
2What is the motivation of this study? This article came out in 2014, and it attempts to give a global overview of how different mechanical forces impact stem cell behavior.This will help new students, and new faculty, in this area get a grasp of “where the field is now” before they start their experiments.They give an overview of all the different types of mechanical forces that impact stem cell behavior.They also give some mechanistic information on what internal components of the cells are responsible for translating mechanical cues into biochemical signals.
14Table 2. Tension (Singyuk Hou) Application of tensile strain to cultured MSCsEffect of tensionOsteogensisBMP-2Calcium depositionOsteogenic mRNAIL-6 and IL-8ERKCollagen 1OsteopontinOsteocalcinALP activityP38,PI3Cbfa-1, Ets-1ChondrogensissGAG synthesis rateStretch-activated calcium channel
15Osteogenesis Materials formation from differentiated MSCs: Calcium phosphate (Hydroxyapatite): Major inorganic component of boneCollagen 1: Main organic component of bone,served as nucleation site for mineral components.Osteocalcin: Protein hormonesecreted by osteoblast,marker associated with mineralizationOsteopontin: Protein binding tocell surface receptors,other matrix proteins andcalcium deposits, involved inosteopontin-cell adhesion,signaling and hydroxyapatitecrystal formationBMP-2 (Bone morphogenic protein-2):Protein belonging to TGF-alpha family, a hormonesecreted by osteoblast to stimulate formationof bone
16Enzyme activities in differentiated MSCs (All up-regulated) ALP ( Alkaline Phosphatase): Key enzyme that provides high concentrations of phosphate at the site of mineral deposition; Maker for osteoblast.ERK(Extracellular signal-regulated kinase):Kinase belonging to MAPK (mitogen-activatedprotein kinase) family,involved in MAPK signaling pathwayp38 and PI3: Kinases belonging to MAPK familyTranscription factors expressiondifferentiated MSCs:Cbfa-1 (RunX) and Ets-1: Play important rolesin regulating the expression of a wide varietyof genes responsible for the osteoblastphenotype including osteocalcin, osteopontin,type I collagen and ALPInt J Biol Sci 2012; 8(2):
17Secretion of molecules from other cells: IL6: Cytokine secreted by T cells and macrophages to stimulate immune responseIL8: Chemokine produced by macrophages,epithelial cells, airway smooth muscle cells,endothelial cells and so forthThey :---Bind to RANKL---Inhibit bone resorption (decompositionof bone minerals and collagen into blood)
18ChondrogensissGAG (sulphated glycosaminoglycan) : Chondrocytes secret chondroitin ( sGAG)to produce and maintain the cartilaginous matrix, rate of sGAG synthesis is markerfor chondrogenic differentiation of MSCsStretch-activated calcium ion channel: Regulating intracellular calcium level. sGAG synthesisRate is dependent on the ion channel.
20Conclusions, Perspectives Mechanical forces on stem cells includes static stiffness and active loading.Various cell-surface receptors are mechano-sensitive, transduced to stem cell behavior through the cytoskeleton.We still don’t fully understand what the mechanical environment is like in vivo.Most studies are isolating 1 force at a time, likely not the case in vivo.
21Grant Teams Soon!Today you will be getting an from CATME. Check Spam folder!CATME will make groups with your responses to that survey.I DO NOT look at the individual information you supply – your responses are confidential, but this is important information to gather to form good teams.5% of your research project grade will be linked to you responding to that website.