CN108949667A - The application of Wnt signal path and its activator - Google Patents
The application of Wnt signal path and its activator Download PDFInfo
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Abstract
The present invention provides the applications of a kind of Wnt signal path and its activator, it is related to field of biotechnology, Wnt signal path provided by the invention is divided into the application in epidermal stem cells in induction stem cells hyperplasia, has filled up the blank that the correlation being divided between epidermal stem cells for Wnt signal path with stem cell proliferation both at home and abroad at present has not been reported；The method that induction stem cells hyperplasia provided by the invention is divided into epidermal stem cells, Wnt signal path, which is utilized, can induce stem cell proliferation to be divided into the mechanism of epidermal stem cells, and targeting is strong, and induction success rate is high；Application of the Wnt signal path provided by the invention in wound healing, the mechanism that Wnt signal path can induce stem cell proliferation to be divided into epidermal stem cells is utilized, good basis is provided for the building of vitro tissue engineering skin, it can play the role of accelerating wound healing, new thinking is provided for wound healing in clinical practice, and there is important application value.
Description
Technical field
The present invention relates to field of biotechnology, more particularly, to the application of a kind of Wnt signal path and its activator.
Background technique
Wnt signal path participates in proliferation, differentiation, migration, polarity and apoptosis of cell etc. between processes and adjacent cells
Interaction, be to be present in biology intracorporal one and its conservative signal transduction pathway, occur in embryonic development and disease
Very important effect is played in the process.
Stem cell (stem cell) is a kind of multipotential cell with the of self-replication capacity (self-renewing).?
Under certain condition, it can be divided into multiple functions cell.The stage of development according to locating for stem cell is divided into embryonic stem cell
(embryonic stem cell, ES cell) and adult stem cell (somatic stem cell).According to the development of stem cell
Potential is divided into three classes: myeloid-lymphoid stem cell (totipotent stem cell, TSC), multipotential stem cell (pluripotent stem
) and unipotent stem cell (unipotent stem cell) (specially can stem cell) cell.Stem cell (Stem Cell) be it is a kind of not
Sufficiently differentiation, still immature cell have the potential function for regenerating various histoorgans and human body, and medical field is known as " general-purpose
Cell ".
Wherein, umbilical cord mesenchymal stem cells (Mesenchymal Stem Cells, MSCs), which refer to, is present in umbilical cord
One of band tissue versatile stem cell, it can be divided into many kinds of histocytes, have wide potential applicability in clinical practice.Navel
Band mescenchymal stem cell differentiation potential with higher, can be broken up to multiple directions.It bone, cartilage, muscle, tendon,
There is wide potential applicability in clinical practice in terms of the organizational projects such as ligament, nerve, liver, endothelium and cardiac muscle.It has been reported that from people's umbilical cord
Umbilical cord mesenchymal stem cells are isolated, and cell content, proliferative capacity are better than mesenchymal stem cell, immunogenicity compares marrow
Mescenchymal stem cell is low, and has many advantages, such as that materials are convenient, no ethics dispute, therefore increasingly by research workers
Concern.
Currently, the influence that Wnt signal path breaks up stem cell to epidermal stem cells, especially umbilical cord mesenchymal stem cells
The influence broken up to epidermal stem cells has not been reported.
Therefore, how to promote stem cell to epidermal stem cells differentiation using regulation Wnt signal path and utilize regulation Wnt
Signal path wound healing has become the hot spot of research.
In view of this, the present invention is specifically proposed.
Summary of the invention
The first purpose of this invention is that providing Wnt signal path is divided into epidermal stem cells in induction stem cells hyperplasia
In application；
Second object of the present invention is to provide a kind of method that induction stem cells hyperplasia is divided into epidermal stem cells；
Third object of the present invention is that providing Wnt signal path activator is divided into epidermis in induction stem cells hyperplasia
Application in stem cell；
Fourth object of the present invention is to provide application of the Wnt signal path in wound healing；It is existing to alleviate
Influence from stem cell to epidermal stem cells that there is Wnt signal path present in technology to break up and logical using regulation Wnt signal
The technical issues of road wound healing correlative study blank.
The present invention provides Wnt signal paths to be divided into the application in epidermal stem cells in induction stem cells hyperplasia.
The present invention also provides a kind of methods that induction stem cells hyperplasia is divided into epidermal stem cells, comprising: dry in activation
While Wnt signal path in cell, epidermal stem cells differentiating inducer is added.
Further, the method for the activation Wnt signal path is that Wnt signal path activator is added.
Further, the Wnt signal path activator is Wnt3a albumen.
The present invention also provides above-mentioned Wnt signal path activator to be divided into epidermal stem cells in induction stem cells hyperplasia
In application.
The present invention also provides application of the Wnt signal path in wound healing.
Further, the method for the wound healing is the building of vitro tissue engineering skin.
Further, the method for the vitro tissue engineering skin building is the plantation culture stem cell on compound rest.
Further, the compound rest is collagen-chitin bracket.
Further, the stem cell is umbilical cord mesenchymal stem cells.
Wnt signal path provided by the invention is divided into the application in epidermal stem cells in induction stem cells hyperplasia, fills up
At present what the correlation between epidermal stem cells had not been reported is divided into for Wnt signal path and stem cell proliferation both at home and abroad
Blank；The method that induction stem cells hyperplasia provided by the invention is divided into epidermal stem cells, Wnt signal path, which is utilized, to lure
The mechanism that stem cell proliferation is divided into epidermal stem cells is led, targeting is strong, and induction success rate is high；Wnt signal provided by the invention
Application of the access in wound healing, Wnt signal path is utilized, and that stem cell proliferation can be induced to be divided into epidermal stem is thin
The mechanism of born of the same parents provides good basis for the building of vitro tissue engineering skin, can play the role of accelerating wound healing, be
Wound healing provides new thinking in clinical practice, has important application value.
Specific embodiment
In order to illustrate more clearly of the present invention, below with reference to preferred embodiment, the present invention is described further.Ability
Field technique personnel should be appreciated that following specifically described content is illustrative and be not restrictive, this should not be limited with this
The protection scope of invention.The person that is not specified actual conditions in embodiment, carries out according to conventional conditions or manufacturer's recommended conditions.Institute
Production firm person is not specified with tool or instrument, is the conventional products that can be obtained by commercially available purchase.
Currently, clinically there are mainly two types of means for wound healing, one is operative treatments, not only costly, and
And patient can be caused on body pain and psychological burden；Another is conservative therapy, coats some external-applied ointments
Liquid medicine etc., but often speed of wound healing is slower, and effect is unsatisfactory.
Therefore, in view of the above-mentioned problems, the present invention provides Wnt signal paths to be divided into epidermal stem in induction stem cells hyperplasia
Application in cell.
Wherein, stem cell is umbilical cord mesenchymal stem cells.
By activation Wnt signal path and inhibit Wnt signal path compared with normal stem cell group, utilizes cell dyeing
Method show that, when Wnt signal path is activated, the quantity that stem cells hyperplasia is divided into epidermal stem cells is most, plays induction and makees
With.
The present invention also provides a kind of methods that induction stem cells hyperplasia is divided into epidermal stem cells, comprising: dry in activation
While Wnt signal path in cell, epidermal stem cells differentiating inducer is added.
Wherein, stem cell is umbilical cord mesenchymal stem cells.
Stem cell differentiating inducer for example can be, but be not limited to vitamin A acid or calcium chloride (CaCl2) one of or two
Kind.
Application activating Wnt signal path can induce stem cells hyperplasia to be divided into the mechanism of epidermal stem cells, activate Wnt
Under conditions of signal path, epidermal stem cells differentiating inducer is added, targeting is stronger, and induced efficiency is higher.
In the present invention, the method for activating Wnt signal path is that Wnt signal path activator is added.
In one preferred embodiment, Wnt signal path activator is Wnt3a albumen.
The present invention also provides above-mentioned Wnt signal path activator to be divided into epidermal stem cells in induction stem cells hyperplasia
In application.
Wherein, stem cell is umbilical cord mesenchymal stem cells.
Application activating Wnt signal path can induce stem cells hyperplasia to be divided into the mechanism of epidermal stem cells, be believed using Wnt
Number Pathway Activation agent activates Wnt signal path, to achieve the purpose that stem cells hyperplasia is induced to be divided into epidermal stem cells.
The present invention also provides application of the Wnt signal path in wound healing.
Wherein, the surface of a wound is skin wound.
Stem cells hyperplasia can be induced to be divided into the mechanism of epidermal stem cells using Wnt signal path, activate Wnt signal logical
Road, induction stem cells hyperplasia are divided into epidermal stem cells, to achieve the purpose that skin wound is made to accelerate healing.
In the present invention, the method for wound healing is the building of vitro tissue engineering skin.
In one preferred embodiment, the method for vitro tissue engineering skin building is that training is planted on compound rest
Support stem cell.
Wherein, compound rest is collagen-chitin bracket, and stem cell is umbilical cord mesenchymal stem cells.
In order to facilitate the clearer understanding present invention, technical solution of the present invention is carried out below in conjunction with embodiment clear
Chu is fully described by, it is clear that described embodiments are some of the embodiments of the present invention, instead of all the embodiments.It is based on
Embodiment in the present invention, it is obtained by those of ordinary skill in the art without making creative efforts every other
Embodiment shall fall within the protection scope of the present invention.
Experimental study of the 1 Wnt signal path of embodiment to UCMSCs Proliferation, Differentiation
1. main experimental materials
Wnt3a and sFRP3 purifying protein；
Umbilical cord mesenchymal stem cells；
Epidermal stem cells differentiating inducer: vitamin A acid and CaCl2；
Antibody: Cyclin-D1, c-myc, β-catenin, p63, CK19, PCNA.
2. experimental setup
The influence of 2.1 Wnt signal activations and inhibition to UCMSCs Proliferation, Differentiation
2.1.1 experimental group
Wnt activation group: Wnt activator, activator dosage are 20ng/mL；
Wnt inhibition group: Wnt inhibitor, inhibitor dosage are 20ng/mL；
Normal group: normal incubation medium.
2.1.2 Wnt signal conditioning culture medium is prepared
Wnt activation group conditioned medium is prepared: being matched with the Wnt3a (R&D systems) that purifying is added in ordinary culture medium
It makes (concentration 100ng/mL), culture carries out on 8 orifice plates for be coated with 1/10ECM glue.
Wnt inhibition group conditioned medium is prepared: preparing (concentration 100ng/ with the sFRP3 that purifying is added in ordinary culture medium
ML), culture carries out on 8 orifice plates for be coated with 1/10ECM glue.
2.1.3 the influence of Wnt signal activation and inhibition cell proliferation
Umbilical cord mesenchymal stem cells are divided into three groups, are cultivated in 10cm culture dish, every group of six repetitions.First group is
Wnt activation group is cultivated using Wnt activation group conditioned medium；Second group is Wnt inhibition group, using Wnt inhibition group condition
Culture medium is cultivated；Third group is Normal group, is cultivated using normal incubation medium.
The every 4d of each group culture cell is passed on and is counted by 1: 3.1,2,4,6 generation cells are taken respectively, are cultivated on slide, for 24 hours
Afterwards, with the BrdU culture solution culture 6h containing 0.1mg/mL.Random counter, analysis BrdU positive cell ratio.
2.1.4 the influence that UCMSCs is broken up in Wnt signal activation and inhibition to epidermal stem cells
In the culture medium of Wnt activation group and Wnt inhibition group be added epidermal stem cells differentiating inducer vitamin A acid and
CaCl2, additional amount 20ng/mL；Normal group add epidermal growth factor culture medium, basic fibroblast growth because
Son, insulin, vitamin A acid and CaCl2, additional amount 20ng/mL.Above-mentioned three groups of cells are placed in 37 DEG C, 5%CO2Saturated humidity
Incubator in routine culture umbilical cord mesenchymal stem cells.
2.1.4.1 morphological observation
After cultivating 5d, the influence that observation regulation Wnt signal breaks up external umbilical cord mesenchymal stem cells to epidermal stem cells,
Morphological observation, comparison of taking pictures under inverted microscope calculate differentiation rate after induction differentiation 5d, carry out statistical analysis comparison.
2.1.4.2 Western blot
Cultivate 5d after, examine each group Wnt signal path in key molecule β-catenin and downstream target gene Cyclin-D1,
The protein expression variation of c-myc, β-catenin, p63, CK19, PCNA, using GAPDH as internal reference.
3. experimental result
It is observed by inverted microscope, Wnt activation group cell is obviously divided from umbilical cord mesenchymal stem cells to epidermal stem cells
Change, six groups of average mark rates reach 84%；Wnt inhibition group cell is seldom divided from umbilical cord mesenchymal stem cells to epidermal stem cells
Change, six groups of average mark rates only have 17%；Normal group cell is less to be divided from umbilical cord mesenchymal stem cells to epidermal stem cells
Change, six groups of average mark rates only have 39%.
Meanwhile it is as shown in the table using Western blot testing result:
From the above it can be seen that Wnt signal path can have an impact the Proliferation, Differentiation of umbilical cord mesenchymal stem cells:
Wnt signal path meeting inducing umbilical cord mesenchymal stem is activated to break up to epidermal stem cells；
Inhibit Wnt signal path that umbilical cord mesenchymal stem cells can be inhibited to break up to epidermal stem cells.
The influence that 2 Wnt signal of embodiment constructs vitro tissue engineering skin
1. main experimental materials:
Collagen-chitin bracket (Chinese Academy of Sciences's offer)；
Umbilical cord mesenchymal stem cells；
Live/Dead staining kit；
ELISA detection kit.
2. experimental setup:
2.1 experimental group
Wnt activation group: Wnt activator, activator dosage are 20ng/mL；
Wnt inhibition group: Wnt inhibitor, inhibitor dosage are 20ng/mL；
Normal group: normal incubation medium.
2.2 cell seeding cultures
Collagen-chitin bracket is taken, after freeze-drying, Co 60 disinfection.
Using the collagen-chitin after sterilizing as bracket, Wnt activation group, Wnt inhibition group and normal control are cultivated in plantation respectively
Group umbilical cord mesenchymal stem cells, planting density are 1 × 106cell/cm2, the group weaver containing umbilical cord mesenchymal stem cells is prepared
Journey skin.
2.3 detection cell proliferation rate-CCK-8
It observes Wnt activation group, Wnt inhibition group and the growth of Normal group cell respectively under inverted microscope, uses
CCK-8 detects cell proliferation rate, observes detection time are as follows: for 24 hours and 72h.
The observation of 2.4 cell survivals --- Live/Dead dyeing
After 1 week, the collagen-chitin bracket for being implanted with umbilical cord mesenchymal stem cells to kind utilizes Live/Dead staining reagent
Box is dyed, Wnt activation group, Wnt inhibition group and just in laser confocal fluorescence microscope observation collagen-chitin bracket
Normal cellular control unit survival condition.
2.5 detection type i collagen changes of contents --- ELISA
After 1 week, using ELISA detection collagen-chitin bracket Wnt activation group, Wnt inhibition group and Normal group I type
Collagen content variation.
The observation of 2.6 cells growth distribution situation in bracket --- DAPI nuclear staining
It is raw in bracket using DAPI nuclear staining observation Wnt activation group, Wnt inhibition group and Normal group cell after 1 week
Long distribution situation.
3. experimental result:
Cell proliferation rate is detected by CCK-8, when for 24 hours, Wnt activation group cell proliferation rate reaches 240%, Wnt inhibition
Group cell proliferation rate only has 118%, and Normal group cell proliferation rate is 141%；In 72h, Wnt activation group cell proliferation rate
Reach 360%, Wnt inhibition group cell proliferation rate and only have 123%, Normal group cell proliferation rate is 166%.
It is observed in collagen-chitin bracket by laser confocal fluorescence microscope, Wnt activation group cell survival is good
Good, number of dead cells is few, and Wnt inhibition group cell survival is general, and number of dead cells is more, and Normal group cell is deposited
Situation living is preferable, and number of dead cells is less.
It is detected in collagen-chitin bracket by ELISA, Wnt activation group type i collagen content increases, Wnt inhibition group I type
Collagen content is less, and Normal group type i collagen content is less.
It is observed by DAPI nuclear staining, Wnt activation group cell upgrowth situation in bracket is good, is evenly distributed, and Wnt inhibits
Group cell upgrowth situation in bracket is general, and distribution uniform, Normal group cell upgrowth situation in bracket is general, distribution
It is more uniform.
It can be seen from the results above that Wnt regulation has an impact to the building of vitro tissue engineering skin:
Activation Wnt signal path can promote the building of vitro tissue engineering skin；
Inhibit Wnt signal path that can inhibit the building of vitro tissue engineering skin.
The foundation of 3 diabetes rat model of embodiment
1. main experimental materials
Cleaning grade healthy SD rat 24, male and female, 7 week old, weight 200-220g, adaptive feeding 1 week.
TUNEL kit；
Streptozotocin STZ；
Antibody: Cyclin-D1, c-myc, β-catenin, p63, CK19, PCNA.
2. experimental setup:
The foundation of 2.1 diabetes models
Diabetes group selection cleaning grade healthy SD rat 18, every group 6, control 6 healthy rats of group selection do not cook sugar
The induction of urine disease, totally 24,7 week old, weight 200-220g, adaptive feeding 1 week.Fasting 16h before diabetes group models, weighing
Empty body weight, tail vein measuring blood sugar of blood extracting concentration, disposable celiac inject streptozotocin STZ (65mg/kg), 72h, 96h,
Random blood sugar is detected using steady Instrument for Measuring Blood Sugar after 120h, measures weight, amount of drinking water, observes ordinary circumstance such as figure and hair
Color change.Every group takes tail vein to measure blood glucose, continuous 3 blood glucose >=16.7mmol/L, and occurs typical " more than three one
It is few " symptom, that is, it can be identified as diabetes rat.
The experimental group of 2.2 adding method thereofs
Control group: umbilical cord mesenchymal stem cells tissue engineering skin (diabetes+surface of a wound+engineered skin)；
Wnt activation group: umbilical cord mesenchymal stem cells tissue engineering skin+Wnt activator (Wnt3a) (diabetes+surface of a wound
+ engineered skin+Wnt3a)；
Wnt inhibition group: umbilical cord mesenchymal stem cells tissue engineering skin+Wnt inhibitor (sFRP3) (diabetes+surface of a wound
+ engineered skin+sFRP3)；
Blank group: umbilical cord mesenchymal stem cells tissue engineering skin (non-diabetic+surface of a wound+engineered skin).
2.3 modelings post-processing
On the basis of above-mentioned diabetes rat model, skin is cut in rat back holostrome and manufactures 2 × 2cm2The surface of a wound, and
Using the fixed surface of a wound of special plastic frame, one layer of ultra-thin silicon glue film is covered finally with the above-mentioned each group surface of a wound, to protect the surface of a wound.
Every component is 1 week postoperative, 2 weeks, 3 time points Wednesday were observed.
2.4 dosing
After rat implantation artificial skin, inject drug at surface of a wound edge using syringe every 3d, syringe needle along
Surface of a wound pellosil outer rim, slightly provokes pellosil, slightly injects drug along surrounding, normal saline dilution Wnt3a and sFRP3, dense
Degree is 100ng/ml, and weak vibrations rat after liquid injection makes medicaments uniformity be covered in the rat surface of a wound.Wnt activation group injects Wnt
Activator Wnt3a, Wnt inhibition group injects Wnt inhibitor sFRP3, control group and blank group injecting normal saline.
2.5 Wound healing rates calculate
1 week after surgery, 2 weeks, 3 weeks respectively observe surface of a wound situation, surface of a wound size are retouched and is printed on sterile transparent film, remember
Record experiment each group surface of a wound area value, calculates Rat Wound Healing rate as follows.
Wound healing rate=(original surface of a wound area residual wound area after-n days)/original surface of a wound area × 100%.
2.6 histological observation --- HE dyeing
Each group cuts surface of a wound skin histology in postoperative 1 week, 2 weeks, 3 weeks, and HE dyeing carries out Histopathology detection, observation
Epidermis, corium rebuild situation and wound inflammation reaction.
2.7 Western blot
Postoperative 1 week, 2 weeks, Cyclin-D1, c-myc, β-in 3 weeks western blot detection each group wound tissue
The expression such as catenin, p63, CK19, PCNA variation, using GAPDH as internal reference.
2.8 apoptotic indexes --- TUNEL method
Wound tissue is cut within postoperative 1 week, 2 weeks, 3 weeks, TUNEL method detects Apoptosis, calculates apoptotic index, proliferation rate.
3. experimental result
Healing postoperative wound surface rate is as shown in the table:
| Group | Postoperative 1 week (%) | Postoperative 2 weeks (%) | Postoperative 3 weeks (%) |
| Blank group | 18 | 45 | 77 |
| Control group | 2 | 5 | 6 |
| Wnt activation group | 33 | 76 | 98 |
| Wnt inhibition group | 3 | 4 | 6 |
It is as follows that observation result is dyed through HE:
It is detected using Western blot:
Postoperative 1 week, each expressing quantity of blank group had no significant change, and control group each group expressing quantity also becomes without obvious
Change, Wnt activation group each group egg expression quantity is white to be increased, and Wnt inhibition group each group expressing quantity is reduced.
Postoperative 2 weeks, each expressing quantity of blank group has to be increased on a small quantity, and control group each group expressing quantity also becomes without obvious
Change, Wnt activation group each group expressing quantity dramatically increases, and Wnt inhibition group each group expressing quantity substantially reduces.
Postoperative 3 weeks, each expressing quantity of blank group has to be increased on a small quantity, and control group each group expressing quantity also becomes without obvious
Change, Wnt activation group each group expressing quantity dramatically increases, and Wnt inhibition group each group expressing quantity substantially reduces.
Cell proliferation rate is detected using TUNEL method:
Postoperative 1 week, blank group cell proliferation rate was 140%, and cellular control unit appreciation rate is 110%, Wnt activation group cell
Appreciation rate is that 240%, Wnt inhibition group cell proliferation rate is 100%.
Postoperative 2 weeks, blank group cell proliferation rate was 260%, and cellular control unit appreciation rate is 110%, Wnt activation group cell
Appreciation rate is that 390%, Wnt inhibition group cell proliferation rate is 100%.
Postoperative 3 weeks, blank group cell proliferation rate was 390%, and cellular control unit appreciation rate is 120%, Wnt activation group cell
Appreciation rate is that 550%, Wnt inhibition group cell proliferation rate is 100%.
It can be seen from the results above that tissue engineering skin development and diabetes rat model modeling containing stem cell at
Function.
Wnt access during compound rest skin wound healing plays a role:
Activate Wnt signal path can wound healing；
Inhibit Wnt signal path that can inhibit wound healing.
In conclusion the method that induction stem cells hyperplasia provided by the invention is divided into epidermal stem cells, is utilized Wnt letter
Number access can induce stem cell proliferation to be divided into the mechanism of epidermal stem cells, and targeting is strong, and induction success rate is high；The present invention mentions
Application of the Wnt signal path of confession in wound healing provides good basis for the building of vitro tissue engineering skin,
It can play the role of accelerating wound healing, new thinking is provided for wound healing in clinical practice, have important
Application value.
Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention., rather than its limitations；To the greatest extent
Pipe present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that: its according to
So be possible to modify the technical solutions described in the foregoing embodiments, or to some or all of the technical features into
Row equivalent replacement；And these are modified or replaceed, various embodiments of the present invention technology that it does not separate the essence of the corresponding technical solution
The range of scheme.
Claims (10)
1.Wnt signal path is divided into the application in epidermal stem cells in induction stem cells hyperplasia.
2. a kind of method that induction stem cells hyperplasia is divided into epidermal stem cells, which is characterized in that the described method includes: activating
While Wnt signal path in stem cell, epidermal stem cells differentiating inducer is added.
3. according to the method described in claim 2, it is characterized in that, the method for the activation Wnt signal path is that Wnt letter is added
Number Pathway Activation agent.
4. according to the method described in claim 3, it is characterized in that, the Wnt signal path activator is Wnt3a albumen.
5. Wnt signal path activator as described in claim 3 or 4 is divided into epidermal stem cells in induction stem cells hyperplasia
Application.
Application of the 6.Wnt signal path in wound healing.
7. application according to claim 6, which is characterized in that the method for the wound healing is vitro tissue engineering
Skin building.
8. application according to claim 7, which is characterized in that the method for the vitro tissue engineering skin building is multiple
Close plantation culture stem cell on bracket.
9. application according to claim 8, which is characterized in that the compound rest is collagen-chitin bracket.
10. application according to claim 1, according to any one of claims 8 is answered at the described in any item methods of claim 2-4
With, which is characterized in that the stem cell is umbilical cord mesenchymal stem cells.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201710361510.5A CN108949667A (en) | 2017-05-22 | 2017-05-22 | The application of Wnt signal path and its activator |
Applications Claiming Priority (1)
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| CN111690612A (en) * | 2019-02-28 | 2020-09-22 | 同济大学 | Method for amplifying human neural precursor cells by regulating Wnt signals and/or Notch signals |
| CN111690612B (en) * | 2019-02-28 | 2023-07-25 | 同济大学 | Method for amplifying human neural precursor cells by modulating Wnt signaling and/or Notch signaling |
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