CN103655614A - Application of adipose tissue progenitor cell for preventing or treating hepatitis - Google Patents
Application of adipose tissue progenitor cell for preventing or treating hepatitis Download PDFInfo
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- CN103655614A CN103655614A CN201210350363.9A CN201210350363A CN103655614A CN 103655614 A CN103655614 A CN 103655614A CN 201210350363 A CN201210350363 A CN 201210350363A CN 103655614 A CN103655614 A CN 103655614A
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Abstract
The invention relates to application of an adipose tissue progenitor cell for preventing or treating hepatitis. Specifically, karyocyte of adipose tissues of the adipose tissue progenitor cell (namely SVF) has extremely excellent hepatitis (especially hepatitis B) preventing or treating effect. A medicine composition provided by the invention is applied to a needed object and has remarkable hepatitis (especially hepatitis B) preventing or treating effect, so that a plurality of surface antigens or antibodies are descended quantitatively, DNA (Deoxyribonucleic Acid) of hepatitis virus is remarkably reduced, AST (Asparate Aminotransferase) and ALT (Alanine Aminotransferase) are lowered, and repair of the liver function is promoted. The invention further provides a method for preventing and treating hepatitis.
Description
Technical field
The invention belongs to stem cell and biomedicine field.Particularly, the present invention relates to the application of fatty tissue CFU-GM in prevention or treatment hepatitis.
Background technology
Hepatitis B is a kind of main disease of China particularly in the world, and its morbidity is dangerous, and progress rapidly, most of patient's prognosis mala, and occur rapidly large area hepatic necrosis, thereby cause liver function to be badly damaged, the function of liver metabolism, excretion and removing toxic substances also has and goes down.Hepatitis B can cause body immunity to decline, and has therefore formed vicious cycle.
For the treatment means of hepatitis B, be at present mainly plasmapheresis and liver transplantation clinically, plasmapheresis expense is huge and dangerous high, and liver transplantation is because donor lacks, and a lot of patients are dead during waiting for transplantation donor.Therefore, liver function support timely and effectively and promotion liver cell regeneration are the important medical procedure that helps liver failure patient to recover voluntarily without liver transplantation.
Stem-cell therapy refers to by stem cell or by the functioning cell of its differentiation generation implants the function that diseased region is lost with compensatory sick cell, or by cell method for disease treatment after external genetic technique operation.Since the development of hepatocyte transplantation treatment technology, treatment cell, from initial allogeneic mature hepatocytes, develops into xenogenesis hepatocyte, fetal liver cell, liver stem cells, bone marrow stem cell, navel blood stem cell and embryonic stem cell.Wherein the stem cell in liver is difficult to extensive use because the difficulty of drawing materials, separation and Culture are complicated; Fetal liver cell and embryonic stem cell, because embryo's source relates to the problems such as ethics, are limited application.
Fatty tissue is considered to storing energy and endocrine organ conventionally, is necessity tissue that soft tissue is filled and liposuction is processed.The effective source that is simultaneously also considered to adult stem cell, because fatty tissue contains multiple CFU-GM, can be divided into multiple pedigree.In fatty tissue, mainly comprising adipose cell, ASCs, vascular endothelial cell, fibroblast, macrophage and extracellular matrix strives SCs and is considered to a kind of thin swollen order of ancestral that shows adipose cell and vascular cell, it between adipose cell, blood vessel is around or in extracellular matrix, can promote lapsing to of fatty tissue.
CFU-GM in fatty tissue (SVF) contains very complicated cell component, comprise other precursor that endotheliocyte, smooth muscle cell, perivascular cell, fibroblast, front adipose cell and differentiation potential are determined etc., the nucleated cell in this class fatty tissue is through cultivating the mescenchymal stem cell that can obtain the extremely strong adipose tissue-derived of plasticity.But lapsing to of fatty tissue is a very very long process, and the adult every year on average adipose cell of nearly 10% left and right is updated, and ASCs is present in the interstitial blood vessel fragment of fatty tissue.
This area does not also have a kind of method of effective treatment hepatitis at present, therefore in the urgent need to exploiting economy, effectively prevents or treat the method for hepatitis.
Summary of the invention
Object of the present invention is just to provide the application of fatty tissue CFU-GM in treatment hepatitis B.
In a first aspect of the present invention, a kind of purposes of fatty tissue CFU-GM is provided, it is used to the pharmaceutical composition that preparation prevents and/or treats hepatitis.
In another preference, described hepatitis is selected from lower group: viral hepatitis, alcoholic hepatitis, autoimmune hepatitis, drug induced hepatitis or its combination.
In another preference, described viral hepatitis is selected from lower group: hepatitis A, hepatitis B, hepatitis C, hepatitis D, hepatitis E.
In another preference, described hepatitis is hepatitis B.
In another preference, described fatty tissue CFU-GM has the arbitrary or various features that is selected from lower group:
(i) more than 30% cell has surface antigen CD29;
(ii) more than 50% cell has surface antigen CD73;
(iii) more than 90% cell has surface antigen CD49d;
(iv) more than 60% cell has surface antigen CD90.
In another preference, more than 35% cell has surface antigen CD29.
In another preference, more than 55% cell has surface antigen CD73.
In another preference, more than 92% cell has surface antigen CD49d.
In another preference, more than 65% cell has surface antigen CD90.
In another preference, described fatty tissue CFU-GM has the arbitrary or various features that is selected from lower group:
(v) cell below 85% has surface antigen CD34;
(vi) cell below 15% has surface antigen CD45.
In another preference, the cell below 80% has surface antigen CD34.
In another preference, the cell below 12% has surface antigen CD45.
In another preference, described fatty tissue CFU-GM secretion is selected from the cytokine of lower group: stem cell factor (HGF), VEGF (VEGF), platelet derived growth factor (PDGF), transforming growth factor-beta (TGF-β), M-CSF (GM-CSF), interleukin-2 (IL-2), IL-10 INTERLEUKIN-10 (IL-10) or its combination in any.
In another preference, the concentration >=0.5ng/ml of the stem cell factor (HGF) of fatty tissue CFU-GM secretion.
In another preference, the concentration >=35pg/ml of the VEGF (VEGF) of fatty tissue CFU-GM secretion, preferably >=40pg/ml.
In another preference, the concentration >=150pg/ml of the transforming growth factor-beta (TGF-β) of fatty tissue CFU-GM secretion, preferably >=180pg/ml.
In another preference, the concentration >=15pg/ml of the interleukin-2 (IL-2) of fatty tissue CFU-GM secretion, preferably >=20pg/ml, more preferably >=30pg/ml.
In another preference, the concentration >=15pg/ml of the IL-10 INTERLEUKIN-10 (IL-10) of fatty tissue CFU-GM secretion, preferably >=20pg/ml, more preferably >=30pg/ml, best >=40pg/ml.
In a second aspect of the present invention, provide a kind of for preventing and/or treating the pharmaceutical composition of hepatitis, described pharmaceutical composition comprises: the fatty tissue CFU-GM of effective dose, and pharmaceutically acceptable carrier.
In another preference, described pharmaceutically acceptable carrier comprises (but being not limited to): saline, buffer, glucose, water, glycerol, ethanol and combination thereof.
In another preference, described pharmaceutical composition is subcutaneous injection reagent.
In another preference, in described subcutaneous injection reagent, the concentration of fatty tissue CFU-GM is 0.1-100 * 10
4individual/ml is preferably 1-10 * 10
4individual/ml is more preferably 2-5 * 10
5individual/ml.
In a third aspect of the present invention, a kind of method that prevents and/or treats hepatitis is provided, comprise step: the pharmaceutical composition of using fatty tissue CFU-GM or containing fatty tissue CFU-GM to the object of needs.
In another preference, described object is behaved or non-human mammal.
In another preference, described non-human mammal is Mus, rabbit, cattle, sheep, pig etc.
In another preference, described method comprises step: feed back described fatty tissue CFU-GM to the object vein of needs, or the pharmaceutical composition that contains fatty tissue CFU-GM.
In should be understood that within the scope of the present invention, above-mentioned each technical characterictic of the present invention and can combining mutually between specifically described each technical characterictic in below (eg embodiment), thus form new or preferred technical scheme.As space is limited, at this, tire out and state no longer one by one.
Accompanying drawing explanation
Following accompanying drawing is used for illustrating specific embodiment of the invention scheme, and be not used in, limits the scope of the invention being defined by claims.
Fig. 1 has shown by flow cytometer method the fatty tissue CFU-GM of preparation has been carried out to the analysis result of surface antigen marker expression.
The specific embodiment
The research that inventor's process is extensive and deep, is surprised to find that first, and fatty tissue CFU-GM has the effect of extremely excellent prevention or treatment hepatitis (especially hepatitis B).Particularly, use the pharmaceutical composition that contains fatty tissue CFU-GM of the present invention to the object needing, for hepatitis, have significant prevention or therapeutical effect, can make kinds of surface antigen decline, viral DNA significantly reduces, and lowers ALT, promotes the reparation of liver function.The present invention also provides a kind of prevention and the method for the treatment of hepatitis and the pharmaceutical composition that contains fatty tissue CFU-GM.Completed on this basis the present invention.
Term
As used herein, term " more than " and " below " comprise given figure, for example " more than 95% " refer to >=95%, " below 0.2% " refer to≤0.2%.
Hepatitis
As used herein, term " hepatitis " is optionally from lower group: viral hepatitis, alcoholic hepatitis, autoimmune hepatitis, drug induced hepatitis or its combination.Hepatitis of the present invention is preferably viral hepatitis, and viral hepatitis can be selected from lower group: hepatitis A, hepatitis B, hepatitis C, hepatitis D, hepatitis E.
In the present invention, described hepatitis is preferably hepatitis B.
Fat
Autologous fat is the good source of shaping and antidotal therapy, and fatty tissue material can derive from the positions such as waist, buttocks, abdominal part, thigh, upper arm.Those skilled in the art can adopt general technical method to obtain autologous fat tissue, include, but is not limited to the methods such as suction, operation separation.
In the present invention, fatty tissue or fatty raw material are not particularly limited, and can be the fatty tissuees that derives from any position of animal or human, preferably people's fatty tissue.Preferably, fatty tissue can be the tissue at the positions such as waist, buttocks, abdominal part, thigh, upper arm.
Fatty tissue CFU-GM
Interstitial blood vessel fragment (SVF, Stromal Vascular fraction)
As used herein, term " fatty tissue CFU-GM ", " SVF ", " fatty tissue nucleated cell " or " interstitial blood vessel fragment " can exchange use.
Fatty tissue CFU-GM is the separated a kind of stem cell with multi-lineage potential obtaining from fatty tissue.Fatty tissue CFU-GM can stablize in vitro propagation and decline rate low, it is drawn materials easily, large, the suitable large-scale culture of cylinder storage amount,, wide material sources little to body injury, suitable autotransplantation.Fatty tissue CFU-GM is most important component in the auxiliary fat transplantation of stem cell.By collagenase digesting, the cell mass that separated various kinds of cell mixture forms from fatty tissue is just called interstitial blood vessel fragment.In interstitial blood vessel fragment, containing abundant mesenchymal cell, can be divided into the cell of multiple pedigree, is the optimal seed cells such as regenerative medicine, organizational project,
Those skilled in the art can use general method to carry out separation and the purification of fatty tissue CFU-GM.
As used herein, term " separation method ", " side's inventive method of the present invention ", " separation method of fatty tissue CFU-GM " can exchange use, all refer to obtain the Method and Process of separated fatty tissue CFU-GM from original fatty tissue.Adipose cell material for the fatty tissue CFU-GM obtaining, first washs, and removes hemocyte; Fat is broken, digestion; Remove indigested tissue, obtain fatty filtrate of organizing CFU-GM; The centrifugal fatty tissue CFU-GM that obtains.The fatty tissue CFU-GM obtaining can be for further going down to posterity, cultivation or frozen.
In a preferred embodiment, isolated adipose tissue CFU-GM can comprise step (but being not limited to): the fat after liposuction is rinsed twice repeatedly with PBS, then under 37 ℃ of conditions, use collagenase digesting 30min, after the centrifugal 10min of 1200g, obtain highdensity SVF fragment, wherein mainly comprise Interstitial cell, vascular endothelial cell and parietal cell.In addition, in fatty tissue CFU-GM, also comprise the cell in some blood vessel sources, as leukocyte and erythrocyte etc., between various cells, there is cooperative effect.
The Detection of antigen of fatty tissue CFU-GM
By the fatty tissue CFU-GM that the present invention uses, there is very high purity, be substantially devoid of cell or the stem cell of other types.This can be verified by the detection of cell surface antigen.
Fatty tissue CFU-GM has multiple specific antigen and receptor, mainly contains CD3, CD13, D29, CD34, CD45, CD49e, CD59, CD73, CD90, CD105, HLA-ABC etc.
CD34 antigen is a kind of high glycosylation I type transmembrane protein, it is optionally expressed in mankind hemopoietic stem cell (HSC), CFU-GM (PC) and vascular endothelial cell (EC) surface, with the fatty tissue CFU-GM of CD34, in the ratio of total stem cell, be preferably≤0.2%, more preferably ,≤0.2%.
CD45 is present in the surface of all hematopoietic cells, comprises hematopoietic stem cell and osteoclast.With the fatty tissue CFU-GM of CD45, in the ratio of total stem cell, be preferably≤0.1%.
CD29, CD73, CD49d, CD90 etc. are mainly present in fat mesenchymal stem cell surface.
With the fatty tissue CFU-GM of CD29, in the ratio of total stem cell, be preferably >=30%, more preferably >=32%, best >=35%.
With the fatty tissue CFU-GM of CD73, in the ratio of total stem cell, be preferably >=50%, more preferably >=60%, best >=70%.
With the fatty tissue CFU-GM of CD49d, in the ratio of total stem cell, be preferably >=85%, more preferably >=90%, best >=95%.
With the fatty tissue CFU-GM of CD90, in the ratio of total stem cell, be preferably >=55%, more preferably >=60%, best >=65%.
Those skilled in that art can use purity and the differentiation degree of general method detection fatty tissue CFU-GM, as flow cytometer method.During detection, add different and specific antibody targetedly, antibody can be complete monoclonal or polyclonal antibody, can be also to have immunocompetent antibody fragment, as Fab ' or (Fab) 2 fragments; Heavy chain of antibody; Light chain of antibody; Genetically engineered scFv molecule (people such as Ladner, U.S. Patent No. 4,946,778); Or chimeric antibody, as there is murine antibody binding specificity but still retain the antibody from people's antibody moiety.Add antibody to be combined certain hour with the antigen of cell surface, with flow cytometer, cell is carried out to automatic analysis and sorting.
The detection of the emiocytosis factor of fatty tissue CFU-GM
Fatty tissue CFU-GM of the present invention can be secreted cytokine profiles, as stem cell factor (HGF), VEGF (VEGF), platelet derived growth factor (PDGF), transforming growth factor-beta (TGF-β), M-CSF (GM-CSF), interleukin-2 (IL-2), IL-10 INTERLEUKIN-10 (IL-10) etc.Those of ordinary skill in the art can use conventional method to detect the cytokine of secretion.As use conventional ELISA method.
The described fatty tissue CFU-GM secretion that the present invention uses is selected from the cytokine of lower group: stem cell factor (HGF), VEGF (VEGF), platelet derived growth factor (PDGF), transforming growth factor-beta (TGF-β), M-CSF (GM-CSF), interleukin-2 (IL-2), IL-10 INTERLEUKIN-10 (IL-10) or its combination.
In another preference, the concentration >=0.5ng/ml of the stem cell factor (HGF) of fatty tissue CFU-GM secretion.
In another preference, the concentration >=35pg/ml of the VEGF (VEGF) of fatty tissue CFU-GM secretion, preferably >=40pg/ml.
In another preference, the concentration >=150pg/ml of the transforming growth factor-beta (TGF-β) of fatty tissue CFU-GM secretion, preferably >=180pg/ml.
In another preference, the concentration >=15pg/ml of the interleukin-2 (IL-2) of fatty tissue CFU-GM secretion, preferably >=20pg/ml, more preferably >=30pg/ml.
In another preference, the concentration >=15pg/ml of the IL-10 INTERLEUKIN-10 (IL-10) of fatty tissue CFU-GM secretion, preferably >=20pg/ml, more preferably >=30pg/ml, best >=40pg/ml.
Pharmaceutical composition
The present invention also provides a kind of pharmaceutical composition, the fatty tissue CFU-GM that it contains effective dose, and pharmaceutically acceptable carrier.
Conventionally, fatty tissue CFU-GM can be formulated in to nontoxic, inertia with pharmaceutically acceptable aqueous carrier medium in, in normal saline, wherein pH is about 5-8 conventionally, preferably, pH is about 7-8.
As used herein, term " effective dose " or " effective dose " refer to and can produce function or amount active and that can be accepted by people and/or animal to people and/or animal.
As used herein, the composition of " pharmaceutically acceptable " is applicable to people and/or mammal and without excessive bad side reaction (as toxicity, stimulation and allergy), has the material of rational benefit/risk ratio.Term " pharmaceutically acceptable carrier " refers to be used for the treatment of the carrier of agent administration, comprises various excipient and diluent.
The fatty tissue CFU-GM that pharmaceutical composition of the present invention contains safe and effective amount and pharmaceutically acceptable carrier.This class carrier comprises (but being not limited to): saline, buffer, glucose, water, glycerol, ethanol and combination thereof.Conventionally pharmaceutical preparation should match with administering mode, and pharmaceutical composition of the present invention can be made into injection form, for example, with normal saline or contain glucose and the aqueous solution of other adjuvant is prepared by conventional method.Described pharmaceutical composition should be manufactured under aseptic condition.The dosage of active component is treatment effective dose.Pharmaceutical preparation of the present invention also can be made into slow releasing preparation.
The effective dose of fatty tissue CFU-GM of the present invention can change with order of severity of the pattern of administration and disease to be treated etc.The selection of preferred effective dose can be determined (for example, by clinical trial) according to various factors by those of ordinary skills.Described factor includes but not limited to: described pharmacokinetic parameter biological example utilization rate, metabolism, half-life etc.; The order of severity of the disease that patient will treat, patient's body weight, patient's immune state, the approach of administration etc.
Pharmaceutical composition of the present invention is preferably subcutaneous injection reagent.In another preference, in described subcutaneous injection reagent, the concentration of fatty tissue CFU-GM is 0.1-100 * 10
4individual/ml is preferably 1-10 * 10
4individual/ml is more preferably 2 * 10
5individual/ml.
Major advantage of the present invention:
(1) fatty tissue CFU-GM has significant prevention or therapeutical effect for hepatitis (particularly hepatitis B);
(2) fatty tissue CFU-GM declines hepatitis B cell kinds of surface antigen, and viral DNA significantly reduces, and lowers glutamate pyruvate transaminase ALT;
(3) fatty tissue CFU-GM can promote the reparation of liver function.
Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment are only not used in and limit the scope of the invention for the present invention is described.The experimental technique of unreceipted actual conditions in the following example, conventionally according to normal condition as people such as Sambrook, molecular cloning: laboratory manual (New York:Cold Spring Harbor Laboratory Press, 1989) condition described in, or the condition of advising according to manufacturer.
Experiment reagent and consumptive material
Aseptic operation apparatus and consumptive material
Aseptic long handle operation surgical forceps, aseptic 100 micron screen, sterilizing 40 micron screen, centrifuge tube
Aseptic reagent
DMEM (serum-free medium)
Type i collagen enzyme (now with the current): 0.1% collagenase I compound method: take 0.1g collagenase I powder dissolution and do not add in the culture medium of any factor in 100ml, with 37 ℃ of preheatings before.
Sodium chloride injection
The separation of fatty tissue CFU-GM
1. receive fatty tissue
The collecting bottle outer wall of the reception fatty tissue that alcohol wipe with 75% is aseptic; Aseptic needle tubing is drawn deep fat tissue from human body, in 1h, is moved in receiving vessel.
2. subpackage fatty tissue
Each 50ml centrifuge tube subpackage fatty tissue 20ml, 10ml pipet is drawn lower floor's red liquid in fatty collecting bottle, discards, and after remaining upper strata fat is mixed, carries out subpackage.
3. wash fatty tissue
Washing fatty tissue, removes hemocyte.In centrifuge tube, add 20ml sodium chloride injection, tighten lid, acutely rock 3 minutes fully to wash fatty tissue, follow static 3-5 minute, difference is separated, suck lower floor's water; Repeat above operation three times, until subnatant is comparatively limpid.
4. collagenase I digestion
The collagenase I solution that adds the preheating (half an hour is in the shaken cultivation case preheating of 37 ℃ in advance) of the new preparation of equivalent, sealed membrane sealing, acutely rock culture bottle 5～10 seconds, be placed in shaken cultivation case, 37 ℃, 100rpm, digests 40 minutes, every 15 minutes, acutely rock culture bottle 5～10 seconds, until tissue seems comparatively level and smooth.
5. isolated adipose tissue CFU-GM (SVF)
Postdigestive tissue is divided in the centrifuge tube that installs to 50ml with aseptic 100 mesh filter screens, centrifugal 5 minutes of room temperature 1500rpm, the precipitation obtaining is fatty tissue CFU-GM.
6. purify precipitation
After centrifugal, fatty tissue CFU-GM is deposited on centrifuge tube bottom, with pipet, carefully removes the collagenase solution of upper strata oils and fats and lower floor from top to bottom.Attention: leave a small amount of solution above fatty tissue CFU-GM precipitation, in order to avoid disturbance sedimentation cell.Appropriate normal saline re-suspended cell, dispels centrifugal 5 minutes of room temperature 1500rpm.45ml normal saline suspension cell,, room temperature 1500rpm is centrifugal 5 minutes again, adds 10ml normal saline after centrifugal and suspends.After filtering, 40 mesh sieves obtain cell mixture again.
Embodiment 2
The evaluation of fatty tissue CFU-GM
1. the flow cytometer detection of fatty tissue CFU-GM
By enzyme digestion by cell harvesting in centrifuge tube, it is 1 * 10 that cell suspension is adjusted density
5mL-1,800r/min (120g), centrifugal 5min, discards supernatant, with the cold D-Hanks of 4 ℃, rinses re-suspended cell, again by cell suspension with 800r/min, centrifugal 5min, afterwards supernatant discarded.Then with D-Hanks, cell is resuspended to 1mL, add antibody 5～10 μ L, lucifuge, places 30min on ice.With D-Hanks, rinse, centrifugal, abandon supernatant, repeat this flushing process 2～3 times, guarantee, by binding antibody Ex-all is not last, to add the D-Hanks of approximately 200 to 300 μ L to make suspension, with flow cytometer, detect.
The flow cytometer detection of fatty tissue CFU-GM the results are shown in Table 1.
Table 1
By flow cytometer, fatty tissue CFU-GM is carried out the analysis of cell surface antigen marker expression, result shows: in the stem cell of fresh separated, fatty tissue CFU-GM ratio is 60%, and hematopoietic stem cell content is 70%, and cell mixing is more.
2. the detection of the emiocytosis factor
Fatty tissue CFU-GM is cultivated to 48h in specific culturing room, get supernatant and detect.Getting umbilical cord stem cell is matched group, the results are shown in Table 2.
Table 2
Result shows, the cytokine of fatty tissue CFU-GM mixture secretion is greatly more than umbilical cord stem cell.
Embodiment 3
The therapeutic effect of fatty tissue CFU-GM to hepatitis B
Method: the cell of results is injected to 100ml normal saline, be prepared into cell suspension, concentration is 2 * 10
5individual/ml, is used in order to feeding back.
Feed back arrangement of time:
Cell separation same day, feeds back for the first time, and (it is 2 * 10 that stem cell feeds back total amount to adopt vein adoptive therapy
7individual);
Three month, the 6th month, each liposuction 20ml repeats above step, and (it was 2 * 10 that stem cell feeds back total amount
7individual);
Feed back 3rd month after front and feedback, do clinical effectiveness scoring by conventional method or commercially available detection kit June respectively, the curative effect of judgement fatty tissue CFU-GM treatment hepatitis B.
Hepatitis B patient 3 examples, before feeding back, feed back one month respectively at cell, and after three months, blood drawing detects five indexes of hepatitis b, hepatitis B virus DNA and ALT, and its result is as follows.
| Test item | Before feedback | Feed back latter 3 months | Feed back latter 6 months |
| Hepatitis B surface antigen | 3983 | 2925 | 1402 |
| Hepatitis B surface antibody | <2 | <2 | <2 |
| Hepatitis B virus e antigen | 0.258 | 0.182 | 0.201 |
| Hepatitis B e antibody | 0.003 | 0.003 | 0.004 |
| Hepatitis B core antibody | 0.005 | 0.008 | 0.008 |
| Hepatitis B virus DNA | 3.79×10 4 | 4.95×10 3 | 1.02×10 3 |
| Glutamate pyruvate transaminase ALT | 64.2 | 36 | 27 |
Patient 2
| Test item | Before feedback | Feed back latter 3 months | Feed back latter 6 months |
| Hepatitis B surface antigen | 1272 | 1184 | 1811 |
| Hepatitis B surface antibody | <2.0 | <2.0 | <2.0IU/L |
| Hepatitis B virus e antigen | 1189 | 1037 | 888.5 |
| Hepatitis B e antibody | 5.38 | 5.39 | 3.11 |
| Hepatitis B core antibody | 0.005 | 0.005 | 0.007 |
| Hepatitis B virus DNA | 6.57×10 7 | 4.80×10 7 | 7.62×10 5 |
| Glutamate pyruvate transaminase ALT | 78 | 56 | 30 |
Patient 3
| Test item | Before feedback | Feed back latter 3 months | Feed back latter 6 months |
| Hepatitis B surface antigen | 3167 | 2581 | 1970 |
| Hepatitis B surface antibody | <2 | <2 | <2 |
| Hepatitis B virus e antigen | 0.319 | 0.267 | 0.186 |
| Hepatitis B e antibody | 0.002 | 0.003 | 0.004 |
| Hepatitis B core antibody | 0.005 | 0.006 | 0.008 |
| Hepatitis B virus DNA | 545000 | 68100 | 846 |
| Glutamate pyruvate transaminase ALT | 65.8 | 56.9 | 46 |
From above result, find out, the cell mixture of fatty tissue CFU-GM has significant therapeutic effect for hepatitis B, can make kinds of surface antigen decline, and viral DNA significantly reduces, and lowers ALT, has promoted the reparation of liver function.
All documents of mentioning in the present invention are all quoted as a reference in this application, just as each piece of document, are quoted as a reference separately.In addition should be understood that those skilled in the art can make various changes or modifications the present invention after having read above-mentioned teachings of the present invention, these equivalent form of values fall within the application's appended claims limited range equally.
Claims (10)
1. a purposes for fatty tissue CFU-GM, is characterized in that, it is used to the pharmaceutical composition that preparation prevents and/or treats hepatitis.
2. purposes as claimed in claim 1, is characterized in that, described hepatitis is selected from lower group: viral hepatitis, alcoholic hepatitis, autoimmune hepatitis, drug induced hepatitis or its combination.
3. purposes as claimed in claim 1, is characterized in that, described fatty tissue CFU-GM has the arbitrary or various features that is selected from lower group:
(i) more than 30% cell has surface antigen CD29;
(ii) more than 50% cell has surface antigen CD73;
(iii) more than 90% cell has surface antigen CD49d;
(iv) more than 60% cell has surface antigen CD90.
4. purposes as claimed in claim 1, is characterized in that, described fatty tissue CFU-GM has the arbitrary or various features that is selected from lower group:
(v) cell below 85% has surface antigen CD34;
(vi) cell below 15% has surface antigen CD45.
5. purposes as claimed in claim 1, it is characterized in that, described fatty tissue CFU-GM secretion is selected from the cytokine of lower group: stem cell factor (HGF), VEGF (VEGF), platelet derived growth factor (PDGF), transforming growth factor-beta (TGF-β), M-CSF (GM-CSF), interleukin-2 (IL-2), IL-10 INTERLEUKIN-10 (IL-10) or its combination in any.
6. for preventing and/or treating a pharmaceutical composition for hepatitis, it is characterized in that, described pharmaceutical composition comprises: the fatty tissue CFU-GM of effective dose, and pharmaceutically acceptable carrier.
7. pharmaceutical composition as claimed in claim 6, is characterized in that, described pharmaceutical composition is subcutaneous injection reagent.
8. a method that prevents and/or treats hepatitis, is characterized in that, comprises step: use fatty tissue CFU-GM or use the pharmaceutical composition that contains fatty tissue CFU-GM to the object of needs.
9. method as claimed in claim 8, is characterized in that, described object is behaved or non-human mammal.
10. method as claimed in claim 8, is characterized in that, comprises step: feed back described fatty tissue CFU-GM to the object vein of needs, or the pharmaceutical composition that contains fatty tissue CFU-GM.
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