CN1893962A - Autologous treatment of degenerated disc with cells - Google Patents
Autologous treatment of degenerated disc with cells Download PDFInfo
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- CN1893962A CN1893962A CNA2004800333235A CN200480033323A CN1893962A CN 1893962 A CN1893962 A CN 1893962A CN A2004800333235 A CNA2004800333235 A CN A2004800333235A CN 200480033323 A CN200480033323 A CN 200480033323A CN 1893962 A CN1893962 A CN 1893962A
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Abstract
The present invention relates to administering autologous uncultured cells into a diseased intervertebral disc.
Description
Related application
The present invention is the U.S. Patent application No.10/714 that is filed on November 14th, 2003,594 continuation application, and U.S. Patent application No.10/714, the 594th, be filed in the U.S. Patent application No.10/714 on November 13rd, 2003,559 part continuation application.Whole instructions of above-mentioned application are merged in this paper by reference.
Background of invention
Natural disc contains the vertebral pulp (nucleus pulposus) of colloidal substance, and it is on every side around fibrous fibrous ring (annulus fibrosus).Under axial load, vertebral pulp is compressed, and should load and radioactively transfer on the fibrous ring.The laminated essence of fibrous ring has been given hot strength of its height, and therefore makes its load that can respond to transfer be radial expansion.
In the intervertebral disc of health, the cell in the vertebral pulp only accounts for one of about percentage of disc tissue by volume.These cells produce extracellular matrix (ECM), wherein contain the Dan Baijutang (proteoglycan) of high percentage ratio.These Dan Baijutang contain in order to keep the sulphation functional group of water, and therefore the performance of damping can be provided to vertebral pulp.Nucleus pulposus cell also can be secreted the small amounts of cells factor and matrix metalloproteinase (MMPs).These cytokines and MMPs can assist the metabolism of regulation and control nucleus pulposus cell.
(disc degeneration disease, under some situation DDD), the regression gradually of intervertebral disc is that the mechanical instability by the spine other parts causes in the intervertebral disc degeneration disease.In these cases, load that vertebral pulp is increased and pressure make cell (or the macrophage of invading) the above-mentioned cytokine that the release ratio normal amount is bigger in the intervertebral disc.Under other situation of DDD, genetic factor or apoptosis also can cause the reduction of intervertebral disc cells quantity and/or these cytokines and MMP to reach the release of toxicity quantity.In some cases, the pumping action of intervertebral disc may break down (because, for example, the reduction of Dan Baijutang concentration in the vertebral pulp), hindered nutrient substance thus and flowed into intervertebral disc, and refuse flows out intervertebral disc.Ability reduction to cell provides nutrient substance and removes refuse may cause cell viability and metabolism to reduce, and this can cause the further regression of ECM, and the accumulation of high-caliber toxin, may cause nerve stimulation and pain.
Along with the development of DDD, the cytokine and the MMPs of the toxic level that exists in the vertebral pulp begin the ECM that degrades.Particularly, the part that is used to keep water of MMPs (being subjected to the regulation and control of cytokine) beginning scinderin polysaccharide reduces its water hold facility thus.This degraded causes the vertebral pulp pliability to reduce, and therefore can change the situation that the intervertebral disc internal loading distributes, thereby may cause the layering of fibrous ring.These variations have caused more serious mechanical instability, make cell discharge thus even more cytokine, typically, thereby MMPs just caused regulate.Along with the continuation of this destructive cascade and further developing of DDD, intervertebral disc begins projection (" outstanding intervertebral disc (a herniated disc) "), and finally breaks, and causes vertebral pulp to contact with spinal cord, produces pain.
U.S. Patent No. 6,352,557 (" Ferree ") have instructed following method: will treat and use material, for example, nucleus pulposus cell joins from granular (morselized) extracellular matrix that donor obtains, and this combination is expelled in the intervertebral disc.But beginning cell most need be cultivated, and joins in the donor substrate before implanting ill intervertebral disc again.This method can allow sufferer experience independent handling procedure twice, also can postpone the treatment to sufferer.The first road program is a harvesting, and it needs to be cultivated then.After the cultivation, cell is implanted in the patient again.
U.S. Patent No. 6,340,369 (" Ferree II ") have instructed following method: obtain intervertebral disc cells alive in patient, cultivate these cells, they are transplanted in the affected intervertebral disc again.Ferree II further instructs, and these cells can make up with II Collagen Type VI-mucopolysaccharide matrix or type i collagen-mucopolysaccharide matrix, and this depends on that cell harvesting is from vertebral pulp (NP) or fibrous ring (AF).Ferree II also proposes, and before transplanting, one or more treatments is joined in the cell with material.As the substituting source of cell, Ferree proposes to use NP or AF cell precursors cell, chondrocyte or other living cells, they and NP or similar NP or the AF cell of maybe can being divided into of AF cell function.In a word, to cultivate the cell of results before Ferree is taught in and transplants.
Alini, Eur.Spine J., 11 (Supp.2): S215-220 (2002) propose, and the bio-matrix that injection is embedded with cell might recover the functional of intervertebral disc.The experiment of Alini relates to isolated cell from vertebral pulp, and they are cultivated.Alini has also proposed other source of cell, comprises intervertebral disc cells and autologous stem cells from the allos donor.His instruction hint, stem cell may be ideal source, but does not also have known method to cultivate stem cell at present, makes them can be divided into nucleus pulposus cell before implanting.In a word, Alini need cultivate by pair cell before implanting.
Russell (Abstract 27 ISSLS 2003) has reported an experiment, and whether matter (mesenchymal) stem cell (MSCs) can be directed to the intervertebral disc phenotype of chondrocytes between being used for determining.Russell finds that when the adjusting that is subjected to condition of culture, and also add under the situation of TGF-B1, adult MSCs can be induced to differentiate into the chondrocyte phenotype.
Sakai (Abstract 24 ISSLS 2003) has reported whether subtend intervertebral disc autotransplantation MSCs can prevent the experiment that intervertebral disc degeneration is assessed.He uses rabbit, separates MSCs from bone marrow, cultivates for 2 weeks, transplants then.The result shows that intervertebral disc is had the effect of keeping significantly.
Sakai, Biomaterials, 24:3531-3541 (2003) has described a kind of method, and use therein final cell density is 1 * 10
6Cell/ml is expelled to each intervertebral disc by 27 grades of (27-gauge) insulin syringes with 0.04ml solution (wherein being embedded with the MSCs that cultivates from body).Find after transplanting that cell successfully breeds.
Sobajima (Abstract 43 ISSLS 2002) has studied the feasibility at the stem cell therapy of DDD.Isolate people NP cell from the sufferer of experience intervertebral disc operation, it is carried out common cultivation with the MSCs of the sufferer of performing the operation from the experience hip or the muscle derived stem cell that obtains from mice.Data show has cooperative effect between stem cell and the nucleus pulposus cell, and this makes, and proper interior Dan Baijutang is synthetic just to be regulated.
Ganey, Eur Spine J, 11 (Suppl.2): S206-S214 (2002) have reported the surgical operation that carries out in Germany, wherein, and in disc removal art (discectomy) afterwards, from the part harvesting of the intervertebral disc of sufferer.Then these cells are cultivated, later on its transplanting is got back in the patient.
Sander etc. instruct in U.S. Patent Application Publication file 2003/0069639, use and organize live body as the source from what sufferer obtained, to obtain for implantation into the cell in the regression intervertebral disc.
All instruct in the above-cited document and will cultivate by pair cell before implantation, the treatment that this corresponding meeting causes sufferer being in the intervertebral disc in the regression postpones to some extent.
Summary of the invention
The present inventor is developed and (intra-operative) program in a kind of operation, be used for effectively treating degenerative disc disease, this be by will from body not cultured cell (for example, a matter hepatocyte or chondrocyte or fibroblast) be incorporated in the intervertebral disc of sufferer and realize.This program provides direct nursing for treating method for sufferer.
According to one embodiment of the present invention, the present inventor is developed and a kind of method that is used for the treatment of intervertebral disc, wherein, the cell of gathering in the crops from the bone marrow of sufferer is introduced in the intervertebral disc of regression subsequently again, to be divided into vertebral pulp and/or the annulus fibrosis cells that is present in the intervertebral disc, improve the quantity of these cells that exist in the intervertebral disc thus.In some embodiments, cell is implanted to intervertebral disc can carry out after harvesting immediately, make sufferer can avoid following situation: the first road program of carrying out harvesting earlier, wait for that cell cultivated (may need several weeks), and then carry out and to be implanted to the second road program in the intervertebral disc through cultured cells.
Believe cell is incorporated into multiple benefit is arranged in the target intervertebral disc.The basic function of these cells is to produce extracellular matrix.As mentioned above, have multiple factor can cause cell death or dysfunction, it can cause the degraded of this substrate with that.A kind of strategy of rebuilding or producing again extracellular matrix is exactly the quantity that increases the functional intervertebral disc cells of the work that can produce substrate.The inventor believes that plasticity (plasticity) phenomenon of interstital stem cell (MSCs) makes the ideal that they become the cell type that can be divided into intervertebral disc cells after being implanted to the target intervertebral disc select.These cells can become the vertebral pulp (NP) and/or fibrous ring (AF) cell that can produce necessary extracellular matrix in intervertebral disc.In addition, when implanting, cell can make up with other therapeutic agent, and for example, somatomedin is survived in intervertebral disc to help cell.
Therefore, in one aspect of the invention, a kind of method for the treatment of degenerative disc disease in the intervertebral disc is provided, described method comprises: results are from the MSCs of sufferer, it is not cultivated, the MSCs that lives is incorporated in the intervertebral disc of regression of same sufferer, wherein, vertebral pulp and/or annulus fibrosis cells will be bred and be divided into to cell.
In some embodiments, cell is sent separately or is sent by carrier.In other embodiments, cell and extra therapeutic agent or material, for example somatomedin is delivered in the intervertebral disc together.
Detailed Description Of The Invention
Because DDD is successive process, the intervertebral disc in the regression of wherein bestowing cell can be any in a large amount of degenerated states.Therefore, the intervertebral disc in the regression can be complete intervertebral disc.Intervertebral disc in the regression can be the intervertebral disc of giving prominence to (that is, wherein, the part of fibrous ring has projection).Intervertebral disc in the regression can be disruptive intervertebral disc (that is, wherein, fibrous ring is broken, and a large amount of vertebral pulps ooze out).Intervertebral disc in the regression can be stratified (that is, wherein, the adjacent layer of fibrous ring separates).Intervertebral disc in the regression can have crack (that is, wherein, fibrous ring has tiny crack or tears, and can spill thus from the selected molecule of vertebral pulp).In all these degenerated states, the extracellular matrix of AF or NP also can be degraded.
The present invention relates in operation to the regression intervertebral disc of sufferer provide healthy, survive from plastid stroma stem cell (MSC).These cells can be delivered among vertebral pulp or fibrous ring or both, are used to repair and recover every kind of extracellular matrix separately.
The inventor believes that MSCs can provide special benefit for bestowing to the intervertebral disc in the regression, can help its easier ability that survives in the regression in the intervertebral disc in the rugged environment relatively because they have.Especially, MSCs has ideal plasticity level, and it makes them have the ability of breeding and being divided into NP and AF cell.
In one embodiment, MSCs obtains the bone marrow from sufferer self.In other embodiments, fat or muscular tissue can be the sources of MSCs.In some embodiments, the MSCs that will be bestowed to intervertebral disc provides with conc forms.When providing with conc forms, cell can not cultivated.Do not cultivate, spissated MSCs can be easily by centrifugal, filter (selective retention) or immunity absorption (immunoabsorption) obtains.When selecting filtration for use, United States Patent (USP) 6,049, the disclosed method of 026 (" Muschler ") can be used, and the content of this patent is incorporated into this paper by integral body by reference.For example, bone marrow aspirate suspension can pass through porous, bio-compatible, implantable substrate, has the composite bone graft body of organizing CFU-GM (tissue progenitor cells) that enriches content to provide.In some embodiments, be used to filter and the substrate of concentrated MSCs as therapeutic agent by co-administered vertebral pulp or fibrous ring.If this substrate has proper mechanical capacity, the height of the intervertebral disc space that it can be used to recover between degeneration stage and is lost.Described cell can be injected simultaneously, or is injected into the target area of intervertebral disc jointly with substrate.
Be used to gather in the crops MSCs sucking-off the bone marrow volume preferably at about 5cc between about 100cc.In concentration process, use this volume then, to concentrate MSCs.
When selecting for use centrifugal the time, the disclosed method of Connolly et al. can be used.Development of an Osteogenic bone Marrow Preparation, JBJS 71-A (No.5) (June 1989) is incorporated into this paper by integral body by reference.In this rabbit experiment, the Connolly report carries out having produced in centrifugal, the final cell suspending liquid every milliliter average 3.6 * 10 to 7-10ml bone marrow
6Individual nuclear cell.
When using centrifuging process to come concentrating cells, they can be delivered to intervertebral disc with the precipitation form in the suspension.In another embodiment, use carrier to transport cell.Carrier can comprise beadlet, microsphere, nanosphere, hydrogel, gel, polymer, pottery, collagen and platelet glue (platelet gel), the group of their formations of perhaps optional freedom.
The carrier of solid or liquid form can carry cell with different ways.Cell can be embedded into, encapsulated (encapsulate), suspend or adhere to the surface of carrier.In one embodiment, carrier provides nutrient substance with cell encapsulationization, and pair cell provides protection in they are delivered to intervertebral disc the time.After a period of time, the carrier degraded discharges cell in intervertebral disc.The specific form of various carriers hereinafter will be described.
In some embodiments, interstital stem cell is provided in the delayed release device (that is, continuing to send (sustained delivery) device).The prescription of bestowing can comprise delayed release device.Delayed release device is transformed into: can keep the time of an elongated segment in intervertebral disc, and the interstital stem cell that will wherein contain lentamente is discharged in the surrounding.This mode of administration makes interstital stem cell be able to the time that keeps an elongated segment with the treatment effective dose in intervertebral disc.Can also transport one or more extra therapeutic agent by continuing delivery apparatus.
Designed synthetic support, adjusted, made it can attract some cell, and the guide to these cells is provided, made them be able to break up in the target area for example based on fumaric support, and to it.Cell also can be embedded in the support, is injected into the target area then, and can not have influence on the propagation or the viability of cell.After implanting based on fumaric support, it can be along with the time degraded, and operation removes support and do not need further.
Carrier can also comprise hydrogel.After the gelation, cell can be by in the polymer chain of encapsulated water inlet gel.Hydrogel can be sent by the mode of Min. invasion, for example injects to the target area.Hydrogel also can be absorbed by health again.The attribute of hydrogel, for example, the space of degradation time, cell adhesion behavior and extracellular matrix accumulation (spatialaccumulation) etc. can be modified by chemistry and technology and be improved.
Being suitable for hydrogel of the present invention and comprising aqueous gel, that is, is the polymer of feature with the insoluble and hydrophilic in water.See, for example, " Hydrogels ", ConciseEncyclopedia of Polymer Science and Engineering, Eds.Mark et al., the 458-459 page or leaf among the Wiley and Sons (1990), its content is incorporated into this paper by integral body by reference.Though it uses is that optionally it is very beneficial comprising hydrogel, because they often have the character of wanting in a large number in the present invention.Rely on its hydrophilic and aqueous essence, hydrogel can accommodate living cells, interstital stem cell for example, and can offer help to the ability that intervertebral disc is born load.
In one embodiment, hydrogel is thin, pulverous synthetic water gel.Suitable hydrogel shows optimum combinations of attributes, for example, and with the compatibility and the bio-compatibility of the matrix polymer of selecting for use.Hydrogel can comprise one or more in the following substances: polysaccharide, protein, polyphosphazene (polyphosphazene), poly-(oxygen ethylene)-poly-(oxypropylene) block polymer, poly-(oxygen ethylene)-poly-(oxypropylene) block polymer of ethylenediamine, poly-(acrylic acid), the copolymer of poly-(methacrylic acid), acrylic acid and methacrylic acid, poly-(vinyl acetate) and sulfonated polymer.
Usually, these polymer are to small part water soluble solution, for example, and water or have water-alcoholic solutions or its monovalention salt of electrically charged side group.Multiple example with polymer of the acidic pendant groups that can react with cation is arranged, for example, poly-(phosphonitrile), poly-(acrylic acid) and gather (methacrylic acid).The example of acidic-group comprises hydroxy-acid group, sulfonic acid group and halogenated (preferably, fluorizated) alcohol groups.Example with polymer of the alkaline side group that can react with anion is poly-(vinylamine), poly-(vinylpyridine) and gathers (ethylene imidazoles).
According to the present invention, the method for degenerative disc disease in the intervertebral disc that a kind of treatment has vertebral pulp is provided, described method comprises the intervertebral disc of the interstital stem cell of not cultivating from body being bestowed regression.
In one embodiment, before being imparted into intervertebral disc, gather in the crops from the plastid stroma stem cell.
According to an aspect of the present invention, interstital stem cell can be delivered to intervertebral disc space with at least a extra therapeutic agent, for example, is used for the reagent of accessory cell propagation and differentiation.Can have, for example, a kind of extra therapeutic agent (that is, second kind of therapeutic agent) perhaps can have multiple extra therapeutic agent (for example, second kind and the third therapeutic agent).Extra therapeutic agent can with interstital stem cell administration simultaneously.In another embodiment, extra therapeutic agent is being bestowed interstital stem cell administration afterwards to intervertebral disc.In another embodiment, extra therapeutic agent is bestowed in advance, that is, bestowed before bestowing interstital stem cell to intervertebral disc.
Can also transport cell and extra therapeutic agent with same carrier.In some embodiments, cell is in carrier surface, and extra therapeutic agent is placed in carrier inside.In other embodiments, cell can come administration with different carriers with extra therapeutic agent.
Other extra therapeutic agent that can join in the intervertebral disc includes but not limited to: vitamin and other supplementary, hormone, glycoprotein, fibronectin, peptide and protein, carbohydrate (simple and/or complicated), Dan Baijutang, oligonucleotide (justice and/or antisense DNA and/or RNA), bone morphogenetic protein (BMPs), differentiation factor, the antibody antibody of infectious factor, tumor, medicine or hormone (for example, for), gene therapy reagent and antitumor and anticancer agent.Cell and/or other cell through genetic modification also can be comprised substrate into of the present invention.If necessary, agent that relieves the pain (that is, analgesic) and tranquilizer also can mix with the carrier that is used for administration, and are discharged into intervertebral disc space.
In some embodiments, somatomedin is extra therapeutic agent.Term used herein " somatomedin " comprise any can be to other cell, the growth of connective tissue CFU-GM or the differentiation cellular products of regulating especially.Can include but not limited to by somatomedin used according to the invention that the member of fibroblast growth family comprises acid and basic fibroblast growth factor (FGF-1 and FGF-2) and FGF-4; The member of platelet derived growth factor (PDGF) family comprises PDGF-AB, PDGF-BB and PDGF-AA; EGFs, the member of insulin like growth factor (IGF) family comprises IGF-I and IGF-II; The super family of TGF-β comprises TGF-β 1,2 and 3 (comprising MP-52), osteoid inducible factor (OIF), angiogenin, endothelin, hepatocyte growth factor and keratinocyte growth factor; The member of bone morphogenetic protein (BMPs), BMP-1, BMP-3, BMP-2, OP-1, BMP-2A, BMP-2B, BMP-4, BMP-7 and BMP-14; HBGF-1 and HBGF-2; Growth and differentiation factor (GDFs), the member of Hedgelog protein matter family (hedgehogfamily) comprises indica-type (indian), velocity of sound type (sonic) and desert type (desert) Hedgelog protein; ADMP-1; GDF-5; And the member of colony stimulating factor (CSF) family, comprise CSF-1, G-CSF and GM-CSF; And isotype.Somatomedin can for example, comprise in being rich in hematoblastic blood plasma from body, perhaps can obtain from commercial channels.In one embodiment, somatomedin is bestowed with the amount of effective repairing intervertebral discs tissue.
In some embodiments, somatomedin is selected from the group of being made up of TGF-β, bFGF and IGF-1.It is believed that these somatomedin can promote the regeneration of vertebral pulp, maybe can stimulate the propagation and/or the differentiation of chondrocyte, and the secretion of extracellular matrix.In one embodiment, somatomedin is TGF-β.More preferably, TGF-β bestows to the amount between about 5000ng/ml with about 10ng/ml, and for example, approximately 50ng/ml is between about 500ng/ml, and for example, approximately 100ng/ml is extremely approximately between the 300ng/ml.
In one embodiment, at least a in the extra therapeutic agent is TGF-β 1.In one embodiment, another kind of extra therapeutic agent is FGF.
In some embodiments, platelet concentrate is provided as extra therapeutic agent.In one embodiment, the amount of the somatomedin that discharges by platelet is the twice at least (for example, four times) that obtains the amount of finding in the hematoblastic blood.In some embodiments, platelet concentrate is from body.In some embodiments, platelet concentrate is to be rich in hematoblastic blood plasma (PRP).PRP is good, because it contains the somatomedin that can irritate the ECM growth once more, and, because its fibrin matrix provides the support that is suitable for growth of new tissue.
Therefore, according to the present invention, provide the method for degenerative disc disease in the intervertebral disc that a kind of treatment has vertebral pulp, described method comprises:
A) will not cultivate interstital stem cell from body and bestow intervertebral disc in the regression; And
B) at least a extra treatment reagent is bestowed intervertebral disc in the regression by the mode (transdiscally) of passing intervertebral disc.
With regard to purpose of the present invention, " pass intervertebral disc and bestow (transdiscaladministration) " includes but not limited to:
A) preparation is expelled to the vertebral pulp of the intervertebral disc in the regression, for example, the intervertebral disc in the complete relatively regression;
B) preparation is expelled to the fibrous ring of the intervertebral disc in the regression, for example, the intervertebral disc in the complete relatively regression;
C) in the paster that is attached to the fibrous ring outer wall (patch), provide preparation,
D) be arranged in outside the fibrous ring outer wall but providing preparation (" passing bestow (the trans-annular administration) of ring ") with the storage storehouse (depot) of its next-door neighbour's position; And
E) outside being arranged in adjacent vertebral body soleplate but provide preparation (" passing bestow (the trans-annular administration) of soleplate ") with the storage storehouse of its next-door neighbour's position.
Also be according to the present invention, a kind of preparation that is used for the treatment of degenerative disc disease also is provided, described preparation comprises:
A) interstital stem cell of not cultivating from body; And
B) at least a extra therapeutic agent,
Wherein, the amount that exists of described preparation (formulation) is suitable for being imparted in the intervertebral disc in the regression.
Also according to the present invention, provide a kind of preparation that is used for being used for the treatment of degenerative disc disease to be administered to the device of intervertebral disc, described device comprises:
A) contain the chamber of described preparation, described preparation comprises the interstital stem cell and at least a extra therapeutic agent of not cultivating from body; And
B) drug delivery port (delivery port), it is communicated with described chamber fluid, and is suitable for described preparation is administered to intervertebral disc.
In some embodiments, cell can be introduced into (promptly bestowing) in vertebral pulp or fibrous ring, and this depends on which kind of extracellular matrix needs to rebuild.In other embodiments, cell can be introduced in these two zones on the intervertebral disc., can be selected the disc area that is administered to according to cell specific therapeutic agent.
In some embodiments, can pass through pin, for example the pore pin is bestowed cell separately (for example, injection) to intervertebral disc.Perhaps, also available same pore pin is expelled to preparation in the intervertebral disc.In some embodiments, the hole of pin is about 22 grades or littler, thereby reduces the probability that forms projection.For example, the hole of pin can be about 24 grades or littler, thereby the probability that projection is produced further reduces.
Take place if the volume of direct injection cell or preparation is high enough to the situation that can cause vertebral pulp being produced excess pressure, so preferably, before bestowing (that is, direct injection) interstital stem cell, remove at least a portion vertebral pulp.The volume of the vertebral pulp that removes in some embodiments, is similar to the volume that preparation to be injected is arranged basically.The volume of the vertebral pulp that for example, removes can be between about 80-120% of volume of preparation that will injection.In addition, this process also has extra benefit,, has removed the intervertebral disc of some regressions of sufferer to small part that is.
When interstital stem cell was injected into vertebral pulp, the volume of the medicine of administration (that is, being suspended in the preparation of the cell in growth medium or the carrier) had been ideal between the extremely about 3.0ml of 0.5ml approximately, and this comprises the cell that is suspended in growth medium or the carrier.When with the injection of above-mentioned less amount, we believe, volume increase or alternate can not cause can be perceived to vertebral pulp in the increase of pressure.For determining that the factor that the administration medicine volume will be considered comprises the concentration of interstital stem cell in the amount of the size of intervertebral disc, the intervertebral disc that removes and growth medium or the carrier.
Though the present invention is shown in detail, and quote preferred embodiment and described, still, those skilled in the art are to be understood that, under situation about not breaking away from, can carry out multiple change in form and details by the included scope of the present invention of appended claim.
Claims (31)
1. method that is used for the treatment of the degenerative disc disease in the intervertebral disc with vertebral pulp, described method comprise, will from body not cultured cells bestow in the intervertebral disc of regression.
2. before the method for claim 1, wherein in being imparted into described intervertebral disc, described cell is concentrated.
3. method as claimed in claim 2, wherein, described cell is concentrated by centrifugal.
4. method as claimed in claim 2, wherein, described cell is concentrated by filtration.
5. the method for claim 1, wherein use carrier that described cell is bestowed described intervertebral disc.
6. method as claimed in claim 5, wherein, described carrier is selected from the group that is made of beadlet, microsphere, nanosphere, hydrogel, gel, polymer, pottery, collagen and platelet glue.
7. the method for claim 1, wherein extra therapeutic agent is imparted in the described intervertebral disc.
8. method as claimed in claim 7, wherein, described extra therapeutic agent is selected from the group that is made of somatomedin, differentiation factor and supplementary.
9. method as claimed in claim 8, wherein, described extra therapeutic agent is a somatomedin.
10. method as claimed in claim 7 wherein, uses carrier that described extra therapeutic agent and described cell are bestowed in the described intervertebral disc.
11. method as claimed in claim 10, wherein, described carrier is selected from the group that is made of beadlet, microsphere, nanosphere, hydrogel, gel, polymer, pottery, collagen and platelet glue.
12. method as claimed in claim 7 wherein, when described intervertebral disc is bestowed described cell, is bestowed described extra therapeutic agent.
13. method as claimed in claim 7 wherein, before bestowing described cell to described intervertebral disc, is bestowed described extra therapeutic agent.
14. method as claimed in claim 7 wherein, after described intervertebral disc is bestowed described cell, is bestowed described extra therapeutic agent.
15. the method for claim 1, wherein described cell is bestowed in preparation to described intervertebral disc, the volume of described preparation is approximately between the extremely about 10ml of 0.5ml.
16. method as claimed in claim 10, wherein, described carrier comprises hydrogel.
17. method as claimed in claim 10, wherein, described carrier comprises microsphere.
18. the method for claim 1, wherein described extra therapeutic agent is TGF-β.
19. the method for claim 1, wherein described therapeutic agent is a platelet concentrate.
20. the method for claim 1, wherein described cell is imparted in the described vertebral pulp of described intervertebral disc.
21. the method for claim 1, wherein described cell is imparted in the described fibrous ring of described intervertebral disc.
22. the method for claim 1, wherein before described cell is imparted into described intervertebral disc, remove the part of described vertebral pulp.
23. the method for claim 1, wherein bestow described cell by pin.
24. method as claimed in claim 23, wherein, described pin maximum level is about 24 grades.
25. the method for claim 1, wherein described cell is selected from the group that is made of interstital stem cell, chondrocyte and fibroblast.
26. the method for claim 1, wherein described cell comprises interstital stem cell.
27. a preparation that is used for the treatment of degenerative disc disease, described preparation comprises:
A) interstital stem cell of not cultivating from body; And
B) extra therapeutic agent,
Wherein, the amount that exists of described preparation is suitable for being imparted in the intervertebral disc in the regression.
28. preparation as claimed in claim 27, wherein, described interstital stem cell provides with conc forms.
29. preparation as claimed in claim 27, wherein, described extra therapeutic agent is a somatomedin.
30. a device is used for the described preparation of claim 27 is bestowed the intervertebral disc of regression, described device comprises:
A) contain the chamber of described preparation; And
B) be suitable for described preparation is imparted into the drug delivery port of described intervertebral disc.
31. the method for claim 1, wherein described preparation is to bestow less than the amount of about 1ml.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US71455903A | 2003-11-13 | 2003-11-13 | |
| US10/714,559 | 2003-11-13 | ||
| US10/714,594 | 2003-11-14 |
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| CN1893962A true CN1893962A (en) | 2007-01-10 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103013910A (en) * | 2012-10-26 | 2013-04-03 | 中国人民解放军第三军医大学第二附属医院 | Human degenerative intervertebral disc cartilage endplate stem cell, preparation method and application thereof |
| CN110693913A (en) * | 2019-10-18 | 2020-01-17 | 上海交通大学医学院附属第九人民医院 | Use of a substance for inducing fibrosis of nucleus pulposus cells in the preparation of a medicament |
| CN113631173A (en) * | 2019-01-02 | 2021-11-09 | 迈索布拉斯特国际有限公司 | Method for treating lumbago |
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2004
- 2004-11-11 CN CNA2004800333235A patent/CN1893962A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103013910A (en) * | 2012-10-26 | 2013-04-03 | 中国人民解放军第三军医大学第二附属医院 | Human degenerative intervertebral disc cartilage endplate stem cell, preparation method and application thereof |
| CN113631173A (en) * | 2019-01-02 | 2021-11-09 | 迈索布拉斯特国际有限公司 | Method for treating lumbago |
| CN110693913A (en) * | 2019-10-18 | 2020-01-17 | 上海交通大学医学院附属第九人民医院 | Use of a substance for inducing fibrosis of nucleus pulposus cells in the preparation of a medicament |
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