CN104630139A - Application of vibration stimulation in regulation of in vitro osteogenesis and adipogenic differentiation of bone marrow-derived mesenchymal stem cells - Google Patents
Application of vibration stimulation in regulation of in vitro osteogenesis and adipogenic differentiation of bone marrow-derived mesenchymal stem cells Download PDFInfo
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- CN104630139A CN104630139A CN201510049427.5A CN201510049427A CN104630139A CN 104630139 A CN104630139 A CN 104630139A CN 201510049427 A CN201510049427 A CN 201510049427A CN 104630139 A CN104630139 A CN 104630139A
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Abstract
The invention discloses application of vibration stimulation in regulation of in vitro osteogenesis and adipogenic differentiation of bone marrow-derived mesenchymal stem cells and belongs to the technical field of cell biotechnology and bone tissue engineering. Osteogenesis differentiation culture and adipogenic differentiation culture are respectively carried out on bone marrow-derived mesenchymal stem cells of people in vitro, vibration stimulation is carried out once a day and every time is 20-45 minutes, and the in vitro osteogenesis differentiation and adipogenic differentiation of bone marrow-derived mesenchymal stem cells are facilitated to be promoted. Vibration stimulation is applied to the bone marrow-derived mesenchymal stem cells, formation of calcium of extracellular matrix and expression of osteogenesis differentiation marker genes of RUNX2 and COL1A1 in mRNA level can be upwards regulated, generation of lipid of epimatrix and expression of adipogenic differentiation marker genes of PPARG2 and CEBPA mRNA can be restrained, and a safe and efficient seed cell source is provided for promoting stem cell osteogenesis differentiation to generate more functional osteoblasts.
Description
Technical field
The invention belongs to cellular biological technique and bone tissue engineer technical field, being specifically related to a kind of high-frequency vibration stimulates in the external Osteoblast Differentiation of regulation and control mesenchymal stem cells MSCs, the application become in fat differentiation.
Background technology
Bone defect healing is an orthopaedics difficult problem all the time.The number that the need that a variety of causes such as disease, natural disaster, accident and war cause accept bone grafting reparation is in rising trend year by year.Traditional Bone Defect Repari method often needs to sacrifice autologous bone and carries out skin grafing and mending, easily causes the wound for district and function limitation; And allosome, bone-xenograft are subject to great restriction because there is the safety problem such as immune rejection, cross infection virus.In recent years, the reparation developed rapidly as Cranial defect of bone tissue engineer provides a kind of new way.The donor tissue utilizing bone tissue engineer to need is few, it is little to damage; Cell can carry out cultivating, increasing in vitro, and no antigen or antigenicity are very micro-; According to repair deficiency needs, can also utilize bionics techniques, implant is made accurate 3D shape, and the reparation for complicated Cranial defect provides new approach.Bone tissue engineer mainly comprises 3 aspects, i.e. the structure of bone guided biomaterial scaffolds, seed cell and tissue-engineered bone.One of them research emphasis is exactly the source of seed cell.Scleroblast is classical seed cell source, but existence propagation, differentiation capability are weak, and the shortcomings such as inconvenience of drawing materials in a large number, can not meet the needs as Seeding Cells in Bone Tissue Engineering.
In recent years, stem cell becomes the focus of bone tissue engineer research.Stem cell is the cell that a class has self and differentiation potential, comprises embryonic stem cell, mescenchymal stem cell and multipotency induced dry-cell, can be divided into various different tissue further, be widely used in regenerative medicine and field of tissue engineering technology.Wherein, mesenchymal stem cells MSCs (Bone marrow-derived mesenchymal stem cells, BM-MSCs) because of its wide material sources, there is multi-lineage potential and very strong self-repairing capability, condition suitable in vitro under can be divided into the features such as scleroblast, chondroblast, adipocyte, become one of seed cell the most frequently used in current bone tissue engineer, in osseous tissue injury repairing, play extremely important effect.But still there are some problems, wherein the important point is that the efficiency of its directed Osteoinductive differentiation is lower.Research shows that mesenchymal stem cells MSCs is to Osteoblast Differentiation with to become fat to break up be not two isolated processes, but there is the mutual equilibrium relationship restricted.Therefore, how to promote mesenchymal stem cells MSCs Osteoblast Differentiation, be suppressed to fat differentiation become research emphasis.
Existing research discloses, and BM-MSCs skeletonization, becomes fat differentiation to be subject in multiple born of the same parents or extracellular signaling molecule and idiosyncratic transcription factor participate in regulation and control jointly.Wherein Runx-2 with PPAR γ is skeletonization respectively, becomes the key transcription factor of both fat directed differentiation and control balance.Runx-2 can promote that BM-MSCs is to osteoblast differentiation; PPAR γ suppresses BM-MSCs Osteoblast Differentiation and promotes lipocyte proliferation.With age, Runx2 expresses reduction, and PPAR γ expresses and increases.Aged animal marrow can produce unknown PPAR γ activator and promote that adipocyte is formed, and is suppressed to bone cell differentiation.
Because BM-MSCs is mechanics sensitive cells, in vitro under suitable mechanical stimulating action, its biological characteristics can sexually revise by generating function, to reach the best requirement of mechanical stimulation, and shows as Osteoblast Differentiation.Wherein, the stress stimulation that vibration waits passive movement to produce can actively affect osseous tissue as a kind of form that is passive, Noninvasive, for promoting in bone tissue engineer research that the scleroblast that stem cell Osteoblast Differentiation produces greater functionality provides safety, efficiently seed cell source.In vivo study result shows, and low-frequency vibration (<100Hz) stimulates can promote bone remoulding.In vitro tests research also shows, low-frequency vibration stimulates can promote mouse bone precursor cells 2T3 differentiation and maturation, Runx-2, ALP genetic expression is raised (see document: M.J. Patel, K.H. Chang, M.C. Sykes, R. Talish, C. Rubin, H. Jo, Low magnitude and high frequency mechanical loading prevents decreased bone formation responses of 2T3 preosteoblasts. Journal of cellular biochemistry 106 (2009) 306-316.1), also can promote that the propagation of MSCs and Osteoblast Differentiation are (see document: D. Pre, G. Ceccarelli, L. Visai, L. Benedetti, M. Imbriani, M.G. Cusella De Angelis, G. Magenes, High-Frequency Vibration Treatment of Human Bone Marrow Stromal Cells Increases Differentiation toward Bone Tissue. Bone marrow research 2013 (2013) 803450.).At present about the research that high-frequency vibration stimulates, report 400 Hz stimulations and can promote that the genetic expression of mouse bone precursor MC3T3-E1 cell Osteoblast Differentiation is (see document: V. Dumas, B. Ducharne, A. Perrier, C. Fournier, A. Guignandon, M. Thomas, S. Peyroche, D. Guyomar, L. Vico, A. Rattner, Extracellular matrix produced by osteoblasts cultured under low-magnitude, high-frequency stimulation is favourable to osteogenic differentiation of mesenchymal stem cells. Calcified tissue international 87 (2010) 351-364.), 1kHz facilitated MSCs Osteoblast Differentiation is (see document: 4 H. Nikukar, S. Reid, P.M. Tsimbouri, M.O. Riehle, A.S. Curtis, M.J. Dalby, Osteogenesis of mesenchymal stem cells by nanoscale mechanotransduction. ACS nano 7 (2013) 2758-2767.).And high-frequency vibration stimulation has no report to the study on regulation of BM-MSCs skeletonization, the differentiation of one-tenth fat simultaneously.
Summary of the invention
The problem of the deficiency the object of the invention is, solve existing regulation and control Osteoblast Differentiation, becoming fat differentiation to exist, provides a kind of high-frequency vibration stimulation being applied to promote that human mesenchymal stem cell is external to Osteoblast Differentiation, the technical scheme being suppressed to fat differentiation.
The technical scheme realizing the object of the invention is: a kind of vibratory stimulation is in the external skeletonization of regulation and control mesenchymal stem cells MSCs, the application become in fat differentiation, and described vibratory stimulation frequency is 750Hz ~ 800Hz.
The particular content of technical solution of the present invention is: mesenchymal stem cells MSCs is carried out Osteoblast Differentiation cultivation, and give once a day, each 20 ~ 45 minutes, frequency be 750Hz ~ 800Hz high-frequency vibration stimulate, continuous 14 days, promote the external Osteoblast Differentiation of mesenchymal stem cells MSCs; Also comprise, mesenchymal stem cells MSCs carried out into fat differentiation culture, and give once a day, each 20 ~ 45 minutes, frequency is that the high-frequency vibration of 750Hz ~ 800Hz stimulates, and continuous 21 days, suppresses the differentiation of mesenchymal stem cells MSCs external one-tenth fat.
Compared with prior art, the invention has the beneficial effects as follows: adopt high vibrational frequency 750 ~ 800Hz region, to BM-MSCs skeletonization and the regulation and control becoming fat differentiation, effectively facilitate BM-MSCs Osteoblast Differentiation, inhibit into fat differentiation, can be used for stem cell biological technology and bone tissue engineer, for promoting that the scleroblast that stem cell Osteoblast Differentiation produces greater functionality provides safety, efficiently seed cell source, and in the treatment of Cranial defect, osteoporosis diseases.
Accompanying drawing explanation
The fluorescence photo figure (scale: 200 μm) of mesenchymal stem cells MSCs after the dyeing of FDA viable cell under inverted fluorescence microscope that Fig. 1 provides for the embodiment of the present invention and comparative example;
Fig. 2 high-frequency vibration stimulates the fluorescence photo figure (scale: 200 μm) after BM-MSCs Osteoblast Differentiation extracellular matrix doped calcium Alizarin red staining under inverted fluorescence microscope;
Fig. 3 is the histogram that high-frequency vibration stimulates to the quantitative analysis of BM-MSCs Osteoblast Differentiation extracellular matrix doped calcium;
Fig. 4 is that high-frequency vibration stimulates the histogram (7 days result of oscillation) of BM-MSCs Osteoblast Differentiation RUNX2, COL1A1 being expressed to impact;
Fig. 5 is that high-frequency vibration stimulates the histogram (14 days result of oscillation) of BM-MSCs Osteoblast Differentiation RUNX2, COL1A1 being expressed to impact;
Fig. 6 is that high-frequency vibration stimulates the fluorescence photo figure (scale: 200 μm) after BM-MSCs one-tenth fat noble cells epimatrix lipidosis oil red O stain under inverted fluorescence microscope;
Fig. 7 is that high-frequency vibration stimulates histogram BM-MSCs being become to the quantitative analysis of fat noble cells epimatrix lipidosis;
Fig. 8 is that high-frequency vibration stimulates histogram BM-MSCs being become to the impact of fat differentiation PPARG2, CEBPA/CEBP-alpha expression.
Embodiment
Below in conjunction with drawings and Examples, technical solution of the present invention is further elaborated.
The present invention adopts vibrational frequency to be the vibratory stimulations of 750 Hz, 800Hz to BM-MSCs, and comparative example is vibrational frequency 30 Hz and does not vibrate.
Reagent involved in each embodiment, method are the conventional reagent in this area and method.People BM-MSCs used in embodiment is purchased from Manassas, U.S. Wei Jili Asia strain library, is first inoculated in 175 CM
2tissue Culture Flask, be incubated at 5% CO
237oC cell culture incubator, basic medium (α-MEM, 10% FBS, 100 U/mL penicillin, 100 μ g/mL Streptomycin sulphates) cultivate.When cytogamy degree reaches about 75%, be inoculated in 96 holes respectively and 12 porocyte culture plates are used as subsequent experimental with 0.25% trypsin digestion cell.
Shaking platform used in the present invention is Hamburg, Germany 3B scientific & technical corporation product, and function generator is the safe and sound letter Products in Shenzhen.
Embodiment 1
High-frequency vibration stimulates BM-MSCs activity influence
Mesenchymal stem cells MSCs inoculates 96 orifice plates by 1000 cell/ holes, is incubated at 5% CO
237oC cell culture incubator, basic medium (α-MEM, 10% FBS, 100 U/mL penicillin, 100 μ g/mL Streptomycin sulphates) cultivate.After 24h, give respectively 30 Hz, 750 Hz and 800Hz, 30min/ days vibratory stimulation as experimental group, non-vibrating is control group (0Hz).Change basic medium every other day.
After 7 days, fluorescein diacetate (FDA) is adopted to detect cytoactive.Often organizing cell adopts 5 μ g/mL FDA, 37 ° of C to hatch 10min, and after PBS cleans twice, under Olympus IX51 inverted fluorescence microscope, fluorescence is taken pictures.As shown in Figure 1, compared with control group, the cells show of vibratory stimulation group goes out obvious fusiform and fibroblast-like form to result, shows that the BM-MSCs under vibratory stimulation is better active.
Embodiment 2
High-frequency vibration stimulates to be affected BM-MSCs Osteoblast Differentiation
Cell cultures mode is with embodiment 1, and mescenchymal stem cell is by 3000 cell/cm
2inoculate 12 orifice plates and be incubated at 5% CO
237oC cell culture incubator, after cell density reaches 95%, be replaced by Osteogenic Induction Medium (low sugar DMEM, 10% FBS, 100 U/mL penicillin, 100 μ g/mL Streptomycin sulphates, 2 × 10
-4m L-AA, 10
-7m dexamethasone, 10
-2m sodium β-glycerophosphate), experimental group is 30,750 and 800Hz, 30min/ days vibratory stimulation groups, and only osteogenic induction group is in contrast.
(1) vibratory stimulation is after 14 days, and extracellular matrix doped calcium thing adopts Alizarin red staining and quantitative analysis.Orifice plate cell 4% paraformaldehyde fixedly spends the night, and hatches 30min after PBS cleaning with 1% sodium alizarinsulfonate (pH=4.3), and ultrapure water to clean after twice optical photographing under Olympus IX51 microscope.In addition, every orifice plate is calcareous with 200 μ L 1% high chloro acid dissolutions, and the absorbance surveying wavelength 420nm place carries out quantitative analysis.
As shown in Figure 2, the dyeing of 800Hz group is apparently higher than control group and 30Hz group for coloration result; Quantitative analysis results is as Fig. 3, and vibratory stimulation affects quantitative analysis to mesenchymal stem cells MSCs epimatrix doped calcium.By mesenchymal stem cells MSCs osteogenic induction and vibratory stimulation 14 days, after Alizarin red staining, adopt the absorbance at the 1% calcareous rear determined wavelength 420nm place of high chloro acid dissolution.Found that the value of high frequency group 750Hz and 800Hz group is apparently higher than control group and low frequency 30Hz group, the value of 30Hz group is significantly lower than control group.Statistical analysis adopts independent sample T inspection, * p < 0.05, * * p < 0.01; Compared with control group,
#p < 0.05,
##p < 0.01.Show that the high-frequency vibration of 14 days stimulates the formation that can promote doped calcium in cell Osteoblast Differentiation epimatrix, and low-frequency vibration stimulation shows as restraining effect.
(2) vibratory stimulation is after 7 days and 14 days respectively, and Trizol method extracts total serum IgE, reverse transcription, by real-time fluorescent quantitative RT-PCR method qualification skeletonization marker gene RUNX2, COL1A1 mrna expression level.Statistical analysis adopts independent sample T inspection, * p < 0.05, * * p < 0.01; Compared with control group,
#p < 0.05,
##p < 0.01.As shown in Figure 4, RUNX2, COL1A1 mRNA relative expression quantity of 30Hz, 750 Hz and 800 Hz groups is all significantly higher than control group to 7 days result of oscillation.As shown in Figure 5, RUNX2, COL1A1 mRNA relative expression quantity of 750Hz and 800Hz group is apparently higher than control group, and the expression of the skeletonization marker gene of 30Hz group then reduces relatively for 14 days result of oscillation.Show that low frequency (30Hz) vibratory stimulation of short-term (7 days) can promote mescenchymal stem cell Osteoblast Differentiation, and long-term low-frequency vibration stimulates the effect having and suppress Osteoblast Differentiation.High-frequency vibration stimulates the promoter action then maintained mescenchymal stem cell Osteoblast Differentiation.
Embodiment 3
Vibratory stimulation becomes fat differentiation impact to BM-MSCs
Cell cultures mode is with embodiment 1, and mescenchymal stem cell is by 3000 cell/cm
2inoculate the 37oC cell culture incubator that 12 orifice plates are incubated at 5% CO2, after cell density reaches 95%, be replaced by adipogenic induction substratum (DMEM in high glucose, 10% FBS, 100 U/mL penicillin, 100 μ g/mL Streptomycin sulphates, 5 × 10
-4m Propenoic acid, 2-methyl, isobutyl ester, 10mg/L Regular Insulin, 10
-4m indomethacin), experimental group is 30,750 and 800Hz, 30min/ days vibratory stimulation groups, and only adipogenic induction group is in contrast.
(1) vibratory stimulation is after 21 days, and the adipocyte that induction produces adopts oil red O stain and quantitative analysis.Orifice plate cell 10% formaldehyde is fixed, with oil red O incubated at room 30min after cleaning, and optical photographing under Olympus IX51 microscope after ultrapure water cleaning.In addition, every orifice plate 200 μ L Virahol lipin dissolving, the absorbance surveying wavelength 510nm carries out quantitative analysis.
See accompanying drawing 6, it is that high-frequency vibration stimulates the fluorescence photo figure (scale: 200 μm) after BM-MSCs one-tenth fat noble cells epimatrix lipidosis oil red O stain under inverted fluorescence microscope.By mesenchymal stem cells MSCs adipogenic induction and vibratory stimulation after 21 days, adopt oil red O stain, found that the dyeing of high frequency group 800Hz group is obviously weaker than control group and low frequency 30Hz group.See accompanying drawing 7, it is that vibratory stimulation affects the result figure of quantitative analysis to mesenchymal stem cells MSCs epimatrix lipidosis, by mesenchymal stem cells MSCs osteogenic induction and vibratory stimulation 21 days, after oil red O stain, Virahol is adopted to dissolve the absorbance at calcareous rear determined wavelength 510nm place.Statistical analysis adopts independent sample T inspection, * p < 0.05, * * p < 0.01; Compared with control group,
#p < 0.05,
##p < 0.01.Found that the value of high frequency group 800Hz group is starkly lower than control group and low frequency 30Hz group.The value of 30Hz group is then significantly higher than control group.Showing that high-frequency vibration stimulates can suppress mescenchymal stem cell epimatrix lipid to be formed, and low-frequency vibration stimulates then has promoter action.
(2) with embodiment 2, adipogenic induction and vibratory stimulation are after 21 days, and real-time fluorescence quantitative RT-PCR identifies into fat marker gene PPARG2, CEBPA/CEBP-α mrna expression level.See accompanying drawing 8, it becomes fat to break up the histogram of PPARG2, CEBPA/CEBP-alpha expression impact for high-frequency vibration stimulates on BM-MSCs.Adopt real-time quantitative RT-PCR method, often organize 3 Duplicate Samples.Statistical analysis adopts independent sample T inspection, * p < 0.05, * * p < 0.01; Compared with control group,
#p < 0.05,
##p < 0.01.Result shows, and PPARG2, CEBPA/CEBP-alpha expression of 750 and 800 Hz groups is all remarkable in control group and 30Hz group, and the expression of low frequency 30Hz group then obviously raises.Show that high-frequency vibration stimulates energy T suppression cell to become the expression of fat marker gene, low-frequency vibration stimulates but has promoter action.
Claims (3)
1. vibratory stimulation is in the external skeletonization of regulation and control mesenchymal stem cells MSCs, the application become in fat differentiation, it is characterized in that: described vibratory stimulation frequency is 750Hz ~ 800Hz.
2. a kind of vibratory stimulation according to claim 1 is in the external skeletonization of regulation and control mesenchymal stem cells MSCs, the application become in fat differentiation, it is characterized in that: mesenchymal stem cells MSCs is carried out Osteoblast Differentiation cultivation, and give once a day, each 20 ~ 45 minutes, vibratory stimulation frequency be 750Hz ~ 800Hz high-frequency vibration stimulate, continuous 14 days, promote the external Osteoblast Differentiation of mesenchymal stem cells MSCs.
3. a kind of vibratory stimulation according to claim 1 is in the external skeletonization of regulation and control mesenchymal stem cells MSCs, the application become in fat differentiation, it is characterized in that: mesenchymal stem cells MSCs is carried out into fat differentiation culture, and give once a day, each 20 ~ 45 minutes, vibratory stimulation frequency be 750Hz ~ 800Hz high-frequency vibration stimulate, continuous 21 days, suppress the external one-tenth fat differentiation of mesenchymal stem cells MSCs.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106176178A (en) * | 2016-08-31 | 2016-12-07 | 张平 | A kind of pulsed joint mechanical load therapeutic instrument |
| US10589268B2 (en) | 2016-06-08 | 2020-03-17 | The Regents Of The University Of California | Method and device for processing tissues and cells |
| US10683480B2 (en) | 2013-06-21 | 2020-06-16 | The Regents Of The University Of California | Microfluidic tumor tissue dissociation device and method |
| US10722540B1 (en) | 2016-02-01 | 2020-07-28 | The Regents Of The University Of California | Microfluidic device and method for shear stress-induced transformation of cells |
-
2015
- 2015-01-31 CN CN201510049427.5A patent/CN104630139A/en active Pending
Non-Patent Citations (4)
| Title |
|---|
| D.PRE等: "High-Frequency Vibration Treatment of Human Bone Marrow Stromal Cells Increases Differentiation toward Bone Tissue", 《BONE MARROW RES》 * |
| HABIB NIKUKAR等: "Osteogenesis of Mesenchymal Stem Cells by Nanoscale Mechanotransduction", 《ACS NANO》 * |
| 张路等: "振动应力刺激骨髓间充质干细胞修复兔骨缺损", 《中国组织工程研究与临床康复》 * |
| 黄钊: "恒定强度1KHz电磁场对大鼠骨髓间充质干细胞增殖及成骨分化作用的探索性研究", 《中国优秀硕士学位论文全文数据库》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10683480B2 (en) | 2013-06-21 | 2020-06-16 | The Regents Of The University Of California | Microfluidic tumor tissue dissociation device and method |
| US11427798B2 (en) | 2013-06-21 | 2022-08-30 | The Regents Of The University Of California | Microfluidic tissue dissociation device and method |
| US10722540B1 (en) | 2016-02-01 | 2020-07-28 | The Regents Of The University Of California | Microfluidic device and method for shear stress-induced transformation of cells |
| US10589268B2 (en) | 2016-06-08 | 2020-03-17 | The Regents Of The University Of California | Method and device for processing tissues and cells |
| US11130127B2 (en) | 2016-06-08 | 2021-09-28 | The Regents Of The University Of California | Method and device for processing tissues and cells |
| CN106176178A (en) * | 2016-08-31 | 2016-12-07 | 张平 | A kind of pulsed joint mechanical load therapeutic instrument |
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Application publication date: 20150520 |