CN108441498A - It is a kind of enhancing human adipose mesenchymal stem cells anti-inflammatory power gene and its application - Google Patents
It is a kind of enhancing human adipose mesenchymal stem cells anti-inflammatory power gene and its application Download PDFInfo
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- CN108441498A CN108441498A CN201810277760.5A CN201810277760A CN108441498A CN 108441498 A CN108441498 A CN 108441498A CN 201810277760 A CN201810277760 A CN 201810277760A CN 108441498 A CN108441498 A CN 108441498A
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- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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- C07K14/475—Growth factors; Growth regulators
- C07K14/4756—Neuregulins, i.e. p185erbB2 ligands, glial growth factor, heregulin, ARIA, neu differentiation factor
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
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- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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Abstract
The invention discloses a kind of gene of enhancing human adipose mesenchymal stem cells anti-inflammatory power and its application, nucleotide sequence such as SEQ ID NO:Shown in 1.The present invention also provides application of the gene of enhancing human adipose mesenchymal stem cells anti-inflammatory power during treating kidney trouble medicine preparation.The gene is glial cell line-derived neurotrophic factor GDNF.The AMSCs modified through GDNF can optimize simple fat mesenchymal stem cell for treatment renal fibrosis, the effect for delaying kidney failure to be in progress.The present invention carries out kidney trouble correlative study with the AMSCs of GDNF modifications for the first time, and the method for optimizing stem-cell therapy has opened up the new approaches of conventional cell treatment.
Description
Technical field
The invention belongs to stem cells and kidney trouble technical field, and it is anti-inflammatory to be related to a kind of enhancing human adipose mesenchymal stem cells
The gene of ability and its application.
Background technology
Kidney region fibrosis is the necessary access of the kidney trouble progress caused by a variety of causes, and end-stage renal disease
(ESRD) common pathological state.Kidney failure is that various chronic renal diseases develop to renal function part caused by the later stage or complete
A kind of pathological state that portion loses.Kidney failure can be divided into acute renal failure and chronic renal failure, the disease progression of acute renal failure
Quickly, typically because of renal blood flow insufficient supply（Such as wound or burn）, kidney function caused by certain factor is blocked it is impaired or
It is to be injured by poisonous substance, causes the generation of acute renal failure.And chronic renal failure main cause is long-term renal lesions, with
The progress of time and disease, the function of kidney is gradually reduced, and causes the generation of kidney failure.The treatment of ESRD relies primarily at present
Dialysis and kidney transplant, but dialysis treatment complication is more, and the semelincident immunization inhibitor for treating after kidney transplant donor shortage and transplanting is all
Therefore the treatment for limiting ESRD inquires into the treatment of kidney region fibrosis, to delay even to block the progress of chronic kidney disease
It is significant.Stem cell be a kind of cell with self-renewing, polyphyly differentiation and hyperproliferation in recent years, with to dry thin
The gradual of born of the same parents' research gos deep into, and people start the treatment that stem cell is applied to a variety of diseases such as the heart, brain, and stem cell is between kidney
The research of matter fibrosis is also that the treatment of chronic kidney disease presents new direction.
Inflammatory reaction is developed to chronic kidney disease progression always through acute renal failure, effective to inhibit inflammation anti-
It answers, effect of the research macrophage in acute renal failure and chronic kidney disease and lapses to, can promote between stem-cell therapy kidney
The progress of matter fibrosis.Currently, research is even in animal experiment stage, the injection dosage and treatment time of stem cell
Still up for exploring.
Invention content
The object of the present invention is to provide a kind of gene of enhancing human adipose mesenchymal stem cells anti-inflammatory power and its answer
With.The gene can reach the therapeutic purposes for improving kidney fibrosis by improving inflammatory reaction.Through GNDF genetic modification people
Fat mesenchymal stem cell can enhance its regulating power to inflammatory reaction.The method for optimizing simple stem-cell therapy, is opened
The New view of gene therapy kidney trouble is opened up.
Its technical solution is as follows：
A kind of gene of enhancing human adipose mesenchymal stem cells anti-inflammatory power, nucleotide sequence such as SEQ ID NO:Shown in 1.
It is a kind of enhancing human adipose mesenchymal stem cells anti-inflammatory power gene smelting treat kidney trouble medicine preparation during
Using.
Compared with prior art, beneficial effects of the present invention：
The present invention provides one kind capable of enhancing human adipose mesenchymal stem cells（AMSCs）The gene of anti-inflammatory power --- colloid is thin
Born of the same parents derived neurotrophic factor GDNF (ID:2668).The AMSCs modified through GDNF can optimize simple fat mesenchymal stem cell
For treatment renal fibrosis, the effect for delaying kidney failure to be in progress.The present invention carries out kidney with the AMSCs of GDNF modifications for the first time
Popular name for correlative study, the method for optimizing stem-cell therapy have opened up the new approaches of conventional cell treatment.
Specific implementation mode
The technical solution further illustrated the present invention with reference to embodiment.
1. carry out the transfection of GNDF gene overexpressions as carrier using slow virus, viral school valence, transfection concentrations are closed
The control and adjustment of reason.The macrophage in the sources 2.THP-1 is internal by the PMA of debita spissitudo, LPS, INF- γ induction simulation
Inflammatory microenvironment.When macrophage and stem cell are co-cultured, the cells transwell or more inner cell ratio needs
Constantly grope.3. when GDNF-AMSCs being injected to UUO Mouse Kidney fibrosis models being treated, stem cell injection dosage with control
The treatment time is regulated and controled.
(1) stem cell is in that culture (2) slow virus carrier of certain scale is transfected and modified to the gene of stem cell in vitro
（GDNF slow virus carriers structure is completed by Shanghai JiKai Gene Chemical Technology Co., Ltd）.(3) it is filled between the fat of GDNF modifications
The anti-inflammatory power of matter stem cell is enhanced.Modified human adipose mesenchymal stem cells can keep the polynary of stem cell again simultaneously
Stability and the safety of property and recombination.The stem cell of the cell in vitro performance detection invention has good reconstruction work(
Can, the transformation of the Macrophage Inflamatory phenotype in the sources THP-1 can be promoted.Human body is simulated by PMA, LPS and INF- γ
Interior inflammatory microenvironment, THP-1 cells after induction are after AMSCs co-cultivations therewith, M1 macrophage Relevant phenotypes
（TNF-α, iNOS, P<0.05）It is remarkably decreased, part M2 indexs of correlation（IL-4、IL-10；P<0.05）It is apparent to rise.Through GDNF
Fat mesenchymal stem cell after genetic modification can strengthen this transformation so that inflammatory reaction is shown in cellular level
Writing improves.(4) AMSCs and GDNF-AMSCs are transplanted to respectively in UUO (unilateral ureteral obstruction) mouse model body（n=6）,
Observe that gdnf gene can reinforce AMSCs and improve the effect of inflammatory conditions（Stem-cell therapy group inflammation index COX-2, IL-6
It is significantly reduced compared with UUO groups, GDNF-AMSCs improves after treating 7 days to be become apparent from（P<0.05））.
1.GDNF-AMSCs passes through to be co-cultured with the macrophage in the sources THP-1, and M1 types macrophage can be promoted to M2
Type macrophage converts.2. the AMSCs being transformed through GDNF is migrated in UUO mouse bodies, it is found that it can be scorching by improving
Disease reaction is to achieve the purpose that treat kidney region fibrosis.
The present invention can more effectively improve macrophage in body by carrying out genetic modification to fat mesenchymal stem cell
Inflammatory reaction caused by interior, to the progress of more favorable delaying chronic kidney trouble.
The above, only best mode for carrying out the invention, any one skilled in the art is in the present invention
In the technical scope of disclosure, the simple change or equivalence replacement of the technical solution that can be become apparent to each fall within the present invention's
In protection domain.
Sequence table
<110>Xuzhou affiliated hospital of medical university
<120>It is a kind of enhancing human adipose mesenchymal stem cells anti-inflammatory power gene and its application
<160> 1
<170> SIPOSequenceListing 1.0
<210> 1
<211> 3810
<212> DNA
<213>Artificial sequence (Artificial Sequence)
<400> 1
ccgcctccag cgcgcccttg ctgccccgcg cgaccccagg attgcgaact cttgcccctg 60
acctgttggg cggggctccg cgctccagcc atcagcccgg atgggtctcc tggctgggac 120
ttggggcacc tggagttaat gtccaaccta gggtctgcgg agacccgatc cgaggtgccg 180
ccgccggacg ggactttaag atgaagttat gggatgtcgt ggctgtctgc ctggtgctgc 240
tccacaccgc gtccgccttc ccgctgcccg ccggtaagag gcctcccgag gcgcccgccg 300
aagaccgctc cctcggccgc cgccgcgcgc ccttcgcgct gagcagtgac tcaaatatgc 360
cagaggatta tcctgatcag ttcgatgatg tcatggattt tattcaagcc accattaaaa 420
gactgaaaag gtcaccagat aaacaaatgg cagtgcttcc tagaagagag cggaatcggc 480
aggctgcagc tgccaaccca gagaattcca gaggaaaagg tcggagaggc cagaggggca 540
aaaaccgggg ttgtgtctta actgcaatac atttaaatgt cactgacttg ggtctgggct 600
atgaaaccaa ggaggaactg atttttaggt actgcagcgg ctcttgcgat gcagctgaga 660
caacgtacga caaaatattg aaaaacttat ccagaaatag aaggctggtg agtgacaaag 720
tagggcaggc atgttgcaga cccatcgcct ttgatgatga cctgtcgttt ttagatgata 780
acctggttta ccatattcta agaaagcatt ccgctaaaag gtgtggatgt atctgactcc 840
ggctccagag actgctgtgt attgcattcc tgctacagtg caaagaaagg gaccaaggtt 900
cccaggaaat gtttgcccag aatggaagat gaggaccaag gaggcggagg aggaggaaga 960
agaagaggag gaggaggagg aggaggagga ggaggaggaa ggcagccatc atgggagcct 1020
ggtagaggga gatccagcta cagacaactg gacaggagag agagaaaaca gccctctgga 1080
ttctccagga tggcagccga tgtcactaga agctcagggc tgatgttcct ggttggctat 1140
tgccaccatt tcagctgata cagtccacca tcactgatta ccggcgcggt tgcggtggat 1200
gcacttgaac caaaccagtg tatctcctgt gatttgtttt catgtgtccg aagacaccag 1260
ggaaacagag atcctggtgt tgttccttgt tattacgttt tactgctgaa agtaagaggt 1320
ttatttttct gtcactcagt ggagacatac cctggaaagg agaggggaaa aaaaaagcaa 1380
agatacaaga gataatcacc tttgcatttg aaagttgagg cccgaggttt actacaacca 1440
gcatttttgc caacggttgg tgattgattt ccatcacggt gtgtggggtg ggaagaagtt 1500
ggctaggaac caaaaaggct gtgctcatga ttaaacacaa acctgaaggt atttccttta 1560
tgtccttgga aacaggaaac gagttgtggt tttcgccagc attcttgtag gagagaatcg 1620
gggaaggccc cgaactgccc ccgggcaggg agagcccctc aggcctgttg gtttacagag 1680
agacagatgt tacataacca gctccgttga tgcgtggtca ccagtgacca gagaagctac 1740
tcgatgcaat gcatctgttt cagatacaga aatatagaga agatatttat tgaaatttaa 1800
gttattgtta tttattaccg ttcactaatg aatttctctt ttttccctta tttattaaag 1860
tttcttttca aaggtgccaa agtatatgtg ctcgcaaaat gcaaagaaag gtgacaaaag 1920
gaaatttgaa ttgggaacaa gggtccatgc ttttcaaagt attaaaaagt tttttgccag 1980
gcaaaaatca cttactttac ctttttaaga aaatttgtca ttaattttcc ccagatttca 2040
gcatttttcc caatttttat ttgtggagca tctcaggcaa gccccctttc ctggagcagc 2100
gtgcagagac cactggcact tgactttatt tcttccttgc tccattgctg aacagaaatg 2160
tcgtgggctc cacttcctgt tgtctttaag ctcttagtcc cctccacgta tacctatctg 2220
tactatgcat aaccatatgt agaaaaggtt cagttccttt tagtaggtag tcctggattt 2280
aatgctgacc taaaagtaat gtcgacaatg ctgtcaggta gctgccgttc taccgactcc 2340
ctccatccct gcccacccac tgccctcccg agaatatgct ggctgcccag tgcagcccgg 2400
gagacacagg ggccttccag aggtagggtc taccaggtcc tgtacaaccc ctgggctgtc 2460
accgggggtc aacagctgct gctcctatat acccaaacac ctgacagctc cctggggagc 2520
agatggctga gaagggtgct gaggaagcca tattgggacc agccacagcc acacacatgg 2580
agcctcatac ttaggagcgt gctgccttta aatgaaggtg gtcggggcca gtgcagcggc 2640
tcacacccat aatcccaaca ctttggaaag ccaaggtggg aggatctctt gaacccagga 2700
gtttgagacc agcttgggca acatagggag accctgtctc tacagaaact ttaaaaatta 2760
ggcaggcatg atggtgcaca cctgtggtcc cagctactca agaggctgaa ggaggatcac 2820
ttgagtccag aaggtcgagg ctgcagtgag ctgtgatcat gccactgcac tccagcctaa 2880
gtgacagtgc ggtaccctgt ctcaaaaaaa aaaaaaaaaa aaaaaagagg ttggagcagg 2940
aggaagcata ggggcgggaa cagccacctc ctccatgccc tagattgtga atttatcggg 3000
cagccaacac atgtatgaca cactaggccc tgtattacag cttgttacgc atttcataaa 3060
agggattttc attaaggaga taatctatta ctacctacct tagtggctac tagtataaaa 3120
ctatgacaga tttagcaatt aaatgaaata ctggcctcca tcaaataatc atagtaacaa 3180
gaagcagcag ttaccagaca tctgatcccc ttcccccaaa atacccaaat tcttcatggt 3240
tctgcccttc tctgtccttt ctgctcccct tgctcgcctg ggaaatggag gaaaggcctt 3300
ccctctcaca ctgtcttggg atcttgctga gaattcagac tgctcgaaac agtgacaaac 3360
cccagccatc cagtcattcg tggagcacaa tttggatgtg gccccagggg catctgtccc 3420
attcagagaa ccttggcagt gcgatggcca ctgttcccag gcttcaacct cagtgacccc 3480
ccccaacaac tccccatgga gagtccctgc ccaaaaaagc tgtaggatcc aaggggtgtc 3540
aatagctcgt tcccggcatc acctacacac cacaagcagg ttttaatgga agcaagttgc 3600
tccaccaaat ccacaaaagg gtaaagtttg tgatttttct ttatcattgc gatcaccatc 3660
tgataccgta aggagtgcac ttgtttggaa gttctgactt ctctgatctg tcttggtcgt 3720
ttgtgttata aaaccaaagt tctctacaga ctttattttt gtacaatatc attttgtaac 3780
tttttacaaa taaaaactca tttctattgc 3810
Claims (2)
1. a kind of gene of enhancing human adipose mesenchymal stem cells anti-inflammatory power, which is characterized in that its nucleotide sequence such as SEQ
ID NO:Shown in 1.
2. the gene of enhancing human adipose mesenchymal stem cells anti-inflammatory power described in claim 1 treats kidney trouble medicine preparation in smelting
Application in the process.
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| CN201810277760.5A CN108441498A (en) | 2018-03-31 | 2018-03-31 | It is a kind of enhancing human adipose mesenchymal stem cells anti-inflammatory power gene and its application |
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| CN201810277760.5A CN108441498A (en) | 2018-03-31 | 2018-03-31 | It is a kind of enhancing human adipose mesenchymal stem cells anti-inflammatory power gene and its application |
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| CN108441498A true CN108441498A (en) | 2018-08-24 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110004151A (en) * | 2019-04-11 | 2019-07-12 | 徐州医科大学附属医院 | It is a kind of enhance fat mesenchymal stem cell excretion body angiogenesis promoting ability gene and its application |
-
2018
- 2018-03-31 CN CN201810277760.5A patent/CN108441498A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110004151A (en) * | 2019-04-11 | 2019-07-12 | 徐州医科大学附属医院 | It is a kind of enhance fat mesenchymal stem cell excretion body angiogenesis promoting ability gene and its application |
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Application publication date: 20180824 |
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