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Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
MechanobiologyMechanobiology and its Clinical Applicationand its Clinical Application
KeijiKeiji NaruseNaruse, M.D. & Ph.D., M.D. & Ph.D.Professor and ChairProfessor and Chair
Cardiovascular Physiology, Okayama Cardiovascular Physiology, Okayama UnivUniv Grad Grad SchSch MedMedCSO, STREX Inc.CSO, STREX Inc.
OVERVIEWOVERVIEW
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
MECHANOBIOLOGYMECHANOBIOLOGY
MECHANOTRANSDUCTIONMECHANOTRANSDUCTION
REPRODUCTIVE MEDICINEREPRODUCTIVE MEDICINE
Modified from”ICURUS”by HENRY MATISSE
HEARINGHEARING
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
TOUCHTOUCH
JOINTSJOINTS
CARDIOVASCULARCARDIOVASCULAR
REPRODUCTIONREPRODUCTION
MECHANOBIOLOGYMECHANOBIOLOGY
1xG1xG
We are continually exposed to mechanical stimuliWe are continually exposed to mechanical stimuli
TEETHTEETHperiodontal ligament cells Bone
Endothelial cellsEndothelial cells
NO, ET1 etc.NO, ET1 etc.Gene expressionGene expressionMorphological changesMorphological changes
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
Hemodynamic forcesHemodynamic forces
pressurepressurestretchstretch
shear stressshear stress
STRETCHSTRETCH--ACTIVATED ACTIVATED ION CHANNELION CHANNEL
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
Biomedical EngineeringBiomedical Engineering
MEMSMEMSBiomedicalBiomedical
SOFT LITHOGRAPHYSOFT LITHOGRAPHY•• MEMS(MEMS(micro electro mechanical systems))
MechanobiologyMechanobiology
•• PDMS PDMS ((polydimethylsiloxanepolydimethylsiloxane))•• nmnm--mmmm•• MeritsMerits
–– TransparentTransparent–– StableStable–– FlexibleFlexible–– High throughput High throughput –– InexpensiveInexpensive
millingmillingphotolithographyphotolithography
Light, EBLight, EBphotomaskphotomask
registregist
Silicon waferSilicon wafer
curecure
PDMSPDMS
porepore
lift offlift off
Mechanotransduction
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
Soft LithographySoft Lithography
Stretch chamberStretch chamber
mouldmould
PDMSPDMS
Mechanotransduction
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
Stretch ChamberStretch Chamber
Mechanotransduction
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
Stretch SystemStretch System
1 Hz 20 %Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
StretchStretch--induced Morphological changeinduced Morphological change
1 Hz20 %
0 min0 min
30 min30 min
60 min60 min
120 min120 min
1 Hz, 20 %Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
0 30 60 90 120 150 18005
101520
%
0 30 60 90 120 150 18005
101520
%
0 30 60 90 120 150 18005
101520
%
0 30 60 90 120 150 18005
101520
%
StretchStretch--induced morphological changeinduced morphological change
1 Hz, 20 % 60 min1 Hz, 20 % 60 min
CaCa2+2+ freefree
GdGd3+3+ GdGd3+3+ CaCa2+2+ freefree
1 Hz, 20 %Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
0 min0 min
30 min30 min
60 min60 min
120 min120 min
0 30 60 90 120 150 18005
101520
%
0 30 60 90 120 150 18005
101520
%0 30 60 90 120 150 1800
5101520
%
0 30 60 90 120 150 18005
101520
%
0 30 60 90 120 150 18005
101520
%
0 30 60 90 120 150 18005
101520
%
0 30 60 90 120 150 18005
101520
%
0 30 60 90 120 150 18005
101520
%
StretchStretch--induced morphological changeinduced morphological change
StretchStretch--activated channel dependentactivated channel dependent
Plasma membranePlasma membrane
SA channelSA channel
CaCa2+2+influxinflux
Fura2Fura2
FluorsecenceFluorsecence MicroscopyMicroscopy
Gd blocks SA channel
1 Hz, 20 %Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
StretchStretch--induced Ca responseinduced Ca response
1 Hz, 20 %Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
StretchStretch--induced Ca responseinduced Ca response
(10%)(5%) (15%) (20%) (25%)
Br J Pharmacol, 2002
200 400 600 800Time (sec)
00.4
0.6
0.8
1.0
1.2
1.4
1.6
Ratio
(340
/380
)
Stretch for 3 sec
1 Hz, 20 %Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
StretchStretch--induced Ca responseinduced Ca response
0 100 200 300 400 500 6000.4
Time (sec)
Gd3+
(10%)(5%) (15%) (20%) (25%) (10%)(5%) (15%) (20%) (25%)
Br J Pharmacol, 2002
00.4
0.6
0.8
1.0
1.2
1.4R
atio
(340
/380
)
Stretch for 3 sec
1 Hz, 20 %Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
StretchStretch--induced Ca responseinduced Ca response
StretchStretch--activated channel dependentactivated channel dependent
•• MscLMscL, , MscSMscS (Non(Non--selective)selective)
••SAKCA (K SAKCA (K ++ selective)selective)
••MidMid--1 (1 (NonNon--selective)selective)••TREK/TRAAK TREK/TRAAK ((KK++ selective)selective)
••TRPs (TRPs (cationcation selective)selective)
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
SA channelSA channel
Science, 285:882Science, 285:882--885 1999885 1999
Molecular Identification of a Eukaryotic, StretchMolecular Identification of a Eukaryotic, Stretch--Activated Nonselective Activated Nonselective CationCation ChannelChannel ::Mid1Mid1
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
SA channelSA channel Mid1Mid1
MDALIIPVTMEVPCDSRGQRMWWAFLASSMVTFFGGLFIILLWRTLKYLW 50MDALIIPVTMEVPCDSRGQRMWWAFLASSMVTFFGGLFIILLWRTLKYLW 50TVCCHCGVKNKEAQKINGGGDTQADGACKPTDEKEENVAAEVGWMTSVKD 100TVCCHCGVKNKEAQKINGGGDTQADGACKPTDEKEENVAAEVGWMTSVKD 100WAGVMISAQTLTGRVLVVLVFALSIGALVIYFIDSSNPIESCQNFYKDFT 150WAGVMISAQTLTGRVLVVLVFALSIGALVIYFIDSSNPIESCQNFYKDFT 150LQIDMAFNVFFLLYFGLRFIAANDKLWFWLEVNSVVDFFTVPPVFVSVYL 200LQIDMAFNVFFLLYFGLRFIAANDKLWFWLEVNSVVDFFTVPPVFVSVYL 200NRSWLGLRFLRALRLIQFSEILQFLNILKTSNSIKLVNLCSIFISTWLTA 250NRSWLGLRFLRALRLIQFSEILQFLNILKTSNSIKLVNLCSIFISTWLTA 250AGFIHLVENSGDPWENFQNNQQLTYWECVYLLMVTMSTVGYGDVYAKTTL 300AGFIHLVENSGDPWENFQNNQQLTYWECVYLLMVTMSTVGYGDVYAKTTL 300GRLFMVFFILGGLAMFASYVPEIIELIGNRKKYGGSYSAVSGRKHIVVCG 350GRLFMVFFILGGLAMFASYVPEIIELIGNRKKYGGSYSAVSGRKHIVVCG 350HITLESVSNFLKDFLHKDRDDVNVEIVFLHNISPNPELEALFKRHFTQVE 400HITLESVSNFLKDFLHKDRDDVNVEIVFLHNISPNPELEALFKRHFTQVE 400FYQGSVLNPHDLARVKIESADACLILANKYCADPDAEDASNIMRVISIKN 450FYQGSVLNPHDLARVKIESADACLILANKYCADPDAEDASNIMRVISIKN 450YHPKIRIITQMLQYHNKAHLLNIPSWNWKEGDDAICLAELKLGFIAQSCL 500YHPKIRIITQMLQYHNKAHLLNIPSWNWKEGDDAICLAELKLGFIAQSCL 500APGLSTMLANLFSMRSFIKIEEDTWQKYYLEGVANEMYTEYLSSAFVGLS 550APGLSTMLANLFSMRSFIKIEEDTWQKYYLEGVANEMYTEYLSSAFVGLS 550FPAVCELVFAKLKLLMIAIEYKSEKRESSILINPGNHVKIQEGTLGFFIA 600FPAVCELVFAKLKLLMIAIEYKSEKRESSILINPGNHVKIQEGTLGFFIA 600SDAKEVKRAFFYCKACHDDITDPKRIKKCGCKRSDAKEVKRAFFYCKACHDDITDPKRIKKCGCKRPKMSIYKRMKLACCFDCPKMSIYKRMKLACCFDC 650650GRSERDCSCMSGSVHSNMDTLERAFPLSSVSVNDCSTSLRAFGRSERDCSCMSGSVHSNMDTLERAFPLSSVSVNDCSTSLRAFEDEQPSTL 700EDEQPSTL 700SPKKKQRNGGMRNSPNSSPKLMRHDPLLIPGNEQIDNMDANVKKYDSTGM 750SPKKKQRNGGMRNSPNSSPKLMRHDPLLIPGNEQIDNMDANVKKYDSTGM 750FHWCPAKDIEKVILTRSEAAMTVLSGHVVVCIFGDVKSALIGLRNLVMPL 800FHWCPAKDIEKVILTRSEAAMTVLSGHVVVCIFGDVKSALIGLRNLVMPL 800RASNFHYHELKHIVFVGSLEYLRREWETLHNFPKVSILPGTPLSRADLRA 850RASNFHYHELKHIVFVGSLEYLRREWETLHNFPKVSILPGTPLSRADLRA 850VNINLCDMCVILSANQNNIDDASLQDKECILASLNIKSMQFDDSIGVLQA 900VNINLCDMCVILSANQNNIDDASLQDKECILASLNIKSMQFDDSIGVLQA 900NSQGFTPPGMDRSSPDNSPVHGLLRQPSITTGANIPIITELVNDSNVQFL 950NSQGFTPPGMDRSSPDNSPVHGLLRQPSITTGANIPIITELVNDSNVQFL 950DQDDDDDPDTELYLTQPFACGTAFAVSVLDSLMSATYFNDNILTLIRTLV 1000DQDDDDDPDTELYLTQPFACGTAFAVSVLDSLMSATYFNDNILTLIRTLV 1000TGGATPELEALIAEENALRGGYSTPQTLANRDRCRVAQLALYDGPFADLG 1050TGGATPELEALIAEENALRGGYSTPQTLANRDRCRVAQLALYDGPFADLG 1050DGGCYGDLFCKALKTYNMFCFGIYRLRDAHLSTPSQCTKRYVITNPPYEF 1100DGGCYGDLFCKALKTYNMFCFGIYRLRDAHLSTPSQCTKRYVITNPPYEF 1100ELVPTDLIFCLMQFDHNAGQSRASLSHSSHSSYSSSKKSSSVHSIPSTAN 1150ELVPTDLIFCLMQFDHNAGQSRASLSHSSHSSYSSSKKSSSVHSIPSTAN 1150RPNRTKTRDSREKQKYVQEDRL 1172RPNRTKTRDSREKQKYVQEDRL 1172
SAKCA
STREX: STREX: StStress Axis ress Axis RReguratedegurated EXEXonon
`
STREX
S0S1S2S3S4S5 S6
COOH
NH2
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
SA channelSA channel
0 10 20 30 4005
1015202530
pressure(-mmHg) P
o (%
)50
`STREX
S0S1S2S3S4S5S6
`S0S1S2S3S4S5S6
TRPM
TRPP
TRPML
TRPC
TRPV
TRPATRPN
Mechanosensitivechannel
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
SA channelSA channel
Transient Receptor Potential channels・ Drosophila Retina・ non-selective cation channel・ 6 putative transmembrane helices ・ ankyrin repeats (N-terminal)・ variety of sensory system・ TRPV1→Thermosensor・ Mechanosensor?・ TRPV2→SA channel?
COS7(Control)10%
20% 40%
10 20 40
COS7(hTRPV2-His) 10%
20% 40% 10 20 40
Transient Rceptor Potential channels
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
COS7(hTRPV2-His)
SA channelSA channel TRPV2TRPV2
1
0 100000 200000
0.3
0.4
0.5
0.6
0.7
0.8
Rat
io (
340nm
/380nm
)
Time (msec)
4
5
6
23
1
2
34
56
ratio380 nm TRPV2-siRNA
Effect of TRPV2-siRNA on stretch-induced [Ca2+]i response
HUVEC
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
SA channelSA channel TRPV2TRPV2
心筋症・心不全 におけるTRPV2の役割
NEW YORK, ManhattanCardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
SA channelSA channel
TRPV2 TG, KO, KI mouseTRPV2 TG, KO, KI mouse
Inducible, Tissue specific, Human KIDouble KO
Wild V2 TG
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
SA channelSA channel TRPV2TRPV2
Ito et al., ARCMB, 2008
“Nano-crack”
Fabrication of reconfigurable protein matrices by crackingNature Materials 4(5):403‐406,2005
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
MECHANOTRANSDUCTIONMECHANOTRANSDUCTION
Conventional cantileverFast Scanning cantilever
10μ10μmm
200μ200μmm
Olympus
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
Fast Scanning Atomic Force MicroscopyFast Scanning Atomic Force Microscopy
plasmid (800 x 600 nm)
Fibronectin(740 x 560 nm)
1 nm10 nm
MscL / WT MscL / G22NOpen mutant
5 nm
Mold & cure
moldcure
Ink
PDMS stretch-chamber
Fibronectin
PDMS
Fibronectin
(A)
(B) (C)
(D) (E)
(F) (G)
(H)
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
Microcontact Printing
StretchStretch--inducedinduced Responses Responses in Patterned in Patterned HUVECHUVEC
Bef
ore
stre
tch
Aft
er s
tret
ch(1
5 m
in)
Aft
er s
tret
ch(6
0 m
in)
Anti- PY Phalloidine
20 um
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
Microcontact Printing on Stretch chamber
StretchStretch--inducedinduced Responses Responses in Patterned in Patterned HUVECHUVEC
00.10.20.30.40.50.60.7
Ratio (A
340/
A38
0)
stretch
35μm×35μm25μm×25μm20μm×20μm10μm×10μm
1min
Z
X-Y
Fura 2
Tyrosine phosphorylation Stretch-induced [Ca2+]i
J Biotech 2008
Coverslip
Cells in microchannel
W=200μm
H=50μm①High shear②Laminar flow
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
MECHANOTRANSDUCTIONMECHANOTRANSDUCTION
CONTROL
SHEAR-STRESS
Nuclear Factor kB
Cell response in microchannel
0.4
0.5
0.6
0.7
0.8
0.9
1
500 600 700 8 00 9 00 10 00
ti me (se c)
rati
o (F
340/
F380
)
0.25μM ATP
9 dyn/ cm2
18 dyn/cm2
[Ca2+]i in response to shear stress
0.4
0.5
0.6
0.7
0.8
0.9
1
500 600 700 8 00 9 00 10 00
ti me (se c)
rati
o (F
340/
F380
)
0.25μM ATP
9 dyn/ cm2
18 dyn/cm2
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
MECHANOTRANSDUCTIONMECHANOTRANSDUCTION
Principle of laminar flow
~500μm in width~ 50μm in hight
W=500μm
H=50μm
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
MECHANOTRANSDUCTIONMECHANOTRANSDUCTION
MECHANOTRANSDUCTIONMECHANOTRANSDUCTION
W=200μm
H=50μm
Principle of laminar flow
PARTCEL(pattented)
“Subcellular positioning of small molecules”
Nature, 2001Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
A
B
C
HHuman uman AAssisted ssisted
RReproductive eproductive TTherapyherapy
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
INFERTILITYINFERTILITY
MechanobiologyMechanobiology in Reproductive Medicinein Reproductive Medicine
••Decreasing in PopulationDecreasing in Population••Death(Death(1,077,0001,077,000)>Birth()>Birth(1,067,0001,067,000))
••Decreasing in BirthrateDecreasing in Birthrate••Total fertility rate : ~1.3Total fertility rate : ~1.3••Various causeVarious cause
••InfertilityInfertility••One in 5One in 5--10 couples10 couples
Male factor=Female factorMale factor=Female factor
••22--3 % : IVF3 % : IVF平成18年6月2日日経新聞
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
INFERTILITY in JAPANINFERTILITY in JAPAN
MechanobiologyMechanobiology in Reproductive Medicinein Reproductive Medicine
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
INFERTILIGY TREATMENTINFERTILIGY TREATMENT
•• Timing treatment (Ovulation)Timing treatment (Ovulation)
•• AIH (Artificial Insemination by Husband)AIH (Artificial Insemination by Husband)
•• IVF (In Vitro Fertilization)IVF (In Vitro Fertilization)–– IVFIVF‐‐conventionalconventional
–– IVFIVF‐‐ICSIICSI((IntracytoplasmicIntracytoplasmic sperm injectionsperm injection))
Sperm
Artificial Insemination Conventional IVF
ICSI
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
Conventional Conventional HHuman uman AAssisted ssisted RReproductive eproductive TTreatment (HART)reatment (HART)
Density gradient
Swim‐up
centrifuge400×g, 20min
Sperm preparationSperm preparation
Culture dishMimeral oil
Culture mediumEmbryo
STATIC CULTURE
Egg cultureEgg culture
REPRODUCTIVE MEDICINEREPRODUCTIVE MEDICINE
NonNon--physiologicalphysiological
1. Microfluidic Sperm Sorter System2. Mechanically Active Embryo Culture System
STREX www.strex.jpwww.strex.jpCardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
REPRODUCTIVE MEDICINEREPRODUCTIVE MEDICINE
STREX www.strex.jpwww.strex.jp
W=500μm, H=50μm
Sperm Sorter /microfluidics
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
REPRODUCTIVE MEDICINEREPRODUCTIVE MEDICINE
Takayama S, Analytical Chemistry, 75:1671-1675, 2003STREX www.strex.co.jpwww.strex.co.jpInitialInitial SortedSorted
00
2020
4040
6060
8080
100100S
perm
Mot
ility
(%
)S
perm
Mot
ility
(%
)
n=10n=10
n=10n=10
aa
bba,b; P<0.05a,b; P<0.05
Sperm Sorter /microfluidics
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
REPRODUCTIVE MEDICINEREPRODUCTIVE MEDICINE
400 x g
Conventional protocol
Motile sperm
SWIM UP !!SWIM UP !!
MFSS & Dilution
+semen medium Dilution
> X 3MFSS
No centrifugation
<岡山大学医学部>
<名古屋大学医学部>Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
REPRODUCTIVE MEDICINEREPRODUCTIVE MEDICINE
No CentrifugationNo Centrifugation
conv
MFSS separation
min 0 30 60 90 120
semen prep
centrifugation density grad Swim up
<名古屋大学医学部>Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
REPRODUCTIVE MEDICINEREPRODUCTIVE MEDICINE
Short processing timeShort processing time
010203040506070
%
59.6%59.6%59/9959/99 46.8%46.8%
51/10951/109
Sperm SorterSperm Sorter conventionalconventional
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
REPRODUCTIVE MEDICINEREPRODUCTIVE MEDICINE
Fertilization rate ↑Fertilization rate ↑
•IRB: Passed 13/5/2005•40 couples with informed consent•> 4 eggs ⇒ ICSI•Embryo transplantation
<プラスチック製>
0.45 mm
0.08 mm
1 JPY
Quartz
Plastic
0.49 mm
0.18 mm
a
b
c
d
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
REPRODUCTIVE MEDICINEREPRODUCTIVE MEDICINE
http://www2.edu.ipa.go.jp/gz/ Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
REPRODUCTIVE MEDICINEREPRODUCTIVE MEDICINE
http://www2.edu.ipa.go.jp/gz/ Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
REPRODUCTIVE MEDICINEREPRODUCTIVE MEDICINE
RAT FALLOPIAN TUBERAT FALLOPIAN TUBE Mouse eggs in fallopian tubeMouse eggs in fallopian tube
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
Shear StressCompressionStretch TurbulenceFriction
Mechanical stresses applied to embryo in oviductMechanical stresses applied to embryo in oviduct
REPRODUCTIVE MEDICINEREPRODUCTIVE MEDICINE
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine
TECSTECS
Tilting Embryo Culture System (TECS) Tilting Embryo Culture System (TECS)
Shear stress(dynes/cm2)
Velocity(mm/sec) 0.003 0.0018
*p=0.035
Blastocysts/total %
Control 63/136 46
TECS 77/130 59
Tilting culture unitControl unit
STREX Inc.
20deg tilting for 10 min, 4-6 mouse eggs/drop
Roll
• Nagoya Univ– M. Sokabe– T. Yamada– X. Sai– K. Wang– H. Inoh– H. Takeda
• Nagoya UnivHospital– H. Ando– D. Shibata
• Harvard Univ– D. Ingber– G.Whitesides
• Michigan Univ– S. Takayama– G. Smith
• ICORP/JST– X. Tang– F. Lopez
• OKAYAMA Univ– S. Mohri– Y. Katanosaka– G. Iribe– A. Yamada– H. Kishio– H. Bao– T. Suemori– T. Komatsu– M. Kajiya
Acknowledgement
Cardiovascular Physiology Okayama University Graduate School of MedicineCardiovascular Physiology Okayama University Graduate School of Medicine