CN101138655B - Farrow skin prosoma organization for renovating skin wound, preparing method and use method thereof - Google Patents
Farrow skin prosoma organization for renovating skin wound, preparing method and use method thereof Download PDFInfo
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Abstract
The present invention provides a fetal pig skin precursor tissue for repairing the skin wound. The fetal pig skin precursor tissue is originated from the inbred strain of all pig species, the fetal pig of the blocked group and the fetal pig of the hybridization breeds. The gestational age of the fetal pig is from 21 days till the birth day, which comprises direct obtaining the fetal pig skin precursor tissue or the fetal pig skin precursor tissue after gene modification. The xenotransplantation is conducted after preparing the tissue into the shape of the cell suspension, the cell mass, the particle or the stamp skin or the big piece of skin. Under proper microenvironment, the present invention comprises the cleaning, the low cell immune response ability, induction of the immune tolerance between the host and the implant (fetal pig skin) or modification in the pig skin precursor tissue. The skin precursor tissue provided in the present invention can grow and develop into a complete skin with the dermis, the epidermis and the appendages of the skin. The present invention can be used in repairing the skin defect caused by various kinds of reasons. The present invention can promote the wound healing; therefore a complete skin is formed.
Description
Technical field
The present invention relates to a kind of dermatoheteroplasty source that is used for wound repair, specifically, the present invention relates to the Farrow skin prosoma organization of using certain pregnant age, the wound surface that is used to repair due to a variety of causes is damaged, rebuild intact skin, reach the physiological reparation of real meaning.
Background technology
The wound surface problem is the key problem of serious burning, trauma care.From body skin source critical shortage, have allosome, the xenogenesis skin of mechanicalness and physiological protective effect, be the biological dressing of present flap coverage, temporary simulated skin function.But grow up allosome or dermatoheteroplasty need overcome intensive immunological rejection, though can prolong time-to-live of allosome or xenograft by suppressing rejection, inducing immune tolerance, are finally still repelled by receptor.
The research that with the seed cell is the organization engineering skin of core has obtained certain progress.But bottlenecks such as the external extensive rapid amplifying of seed cell have limited its application in large tracts of land burning trauma care.And the structure of organization engineering skin is simple relatively, is difficult to reach the purpose of real physiological wound repairing.
Stem cell has reduced immunogenicity, has multidirectional differentiation potential, can directed differentiation be mature tissue's cell under given conditions.Thomson etc. by 5 days blastocyst of artificial fertilization, successfully induce the cell of three germinal layers external, for regenerative medicine has been established new milestone.Report is arranged when being induced to differentiate into sophisticated various histoorgan by stem cell; Yet, are great challenge to various specific accurately inducing of mature tissue from embryonic stem cell.Studies show that induce the ripe skin histology that breaks up and form by stem cell, effectively wound closure, and immunogenicity is low, even non-immunogenicity (autologous stem cells), suitably can rebuild holostrome skin under the situation with skin appendages such as hair follicles.But source of stem cell and amplification in vitro are very limited, and there is technological challenge in accurate directed differentiation, and length consuming time, are unsuitable for the sealing of large tracts of land burning, wound and wound surface.
From the beginning of the nineties in last century, people begin systematically embryonic cell or embryonal tissue to be carried out external processing and transplant to substitute lacking or impaired histoorgan, and these embryonal tissues comprise pancreas, kidney, lungs, heart, small intestinal, hepatocyte precursor and neuron precursor etc.Embryonal tissue has characteristics such as the source is abundant, and growth potential is big, and immunogenicity is low.Application embryo's prosoma organization (Embryonic precursor tissues) carries out xenotransplantation and can solve allograft skin source shortage problem, and it has reduced immunogenicity what is more important, even without immunosuppressant rejection does not take place yet after transplanting.But a large amount of in the past experimentatioies does not all have to overcome fully embryonal tissue forms teratomatous risk.Especially on the larger animal model, carry out clinical before experiment more do not obtain gratifying effect.
Rogers etc. migrate to E15 embryo metanephros in the SD rat omentum majus under not using the immunosuppressant situation, graft can revascularization in homologous adult rat body, histiocyte growth, differentiation, and form form and the structure that is similar to normal kidney, and have certain urinary function.Transplant 10 weeks of back, the form and the structure of transplanting metanephros are all normal.
Transplant in rat E16 after Xu Jian, Zheng Shu Lignum Rhamnellae will be preserved, the capable omentum majus of E17 embryo metanephros, and be aided with the ciclosporin A subcutaneous injection, can form organ, and the performance function.Transplant 3 weeks of back, the visible metanephros well-grown of transplanting in the receptor Mus omentum majus, blood supply is abundant.Nephron and ureter physically well develop, and transplant metanephros and are kidney shape, and quality is soft, and cortex and medullary substance are all known and manifested.Electronic Speculum shows that transplanting back glomerule endotheliocyte, mesangial cell, basement membrane, podocyte and podocytic process morphosis are normal, and near-end renal cells and microvillus, distal renal tubular and collecting tubule epithelial cell physically well develop; Transplant 8 weeks of back, transplanted kidney divides the urinary system amount can reach 16.60 ± 3.65 μ l/h, and creatinine clearance rate can reach 0.501 ± 0.197 μ l/s.
Studies show that of above-described graft about specific embryo age: all should there be the time window an of the best in embryonal tissue in growth and development process, in this narrow time window, particular organization still can become corresponding organ (tissue) by growth promoter after xenotransplantation, do not form teratoma again, and have the characteristics of high growth potential and reduced immunogenicity.
Summary of the invention
The purpose of this invention is to provide a kind of Farrow skin prosoma organization, can be used for covering the reparation of the wound surface that burn, wound etc. cause, reach the effect of rebuilding intact skin.And invention also provides the preparation method and the using method of this Farrow skin prosoma organization.
The present invention is to provide a kind of skin prosoma organization that derives from the tire pig.Tire pig precursor skin histology described here can be the pig kind that derives from different strains, such as: Guizhou pig, Wuzhi Mountain pig, crust horse pig, Rongchang County pig etc.Inbred line also can be a closed colony, or even Hybrid, the tire pig prosoma organization that all can provide the present invention to send out to state.
Farrow skin prosoma organization of the present invention is meant after the accurate period of pregnancy, in 21 days to the Farrow skin prosoma organization that goes out the specific gestational age between the birthday.
The preparation method of Farrow skin prosoma organization of the present invention is as follows:
At first from pregnant age took out the tire pig to the sow body that goes out the birthday in 21 days, cleaning and sterilizing as clean bubble tire pig with PBS, soaks 10min with the normal saline that contains 0.01% bromo geramine then and carries out disinfection;
Strip the holostrome Farrow then, put into the normal saline of 0.005% bromo geramine;
In the process of practical application, according to different wound surface situations, the holostrome Farrow can be made different forms, as shred and make microparticle skin, size is about 1mm
3, perhaps its preparation is become cell suspension or cell mass (being used for big Zhang Yiti or xenogenesis skin covers) by tissue homogenate; Or be prepared into big or small 0.25cm
2-4cm
2Stamp skin book (cover or be attached on the wound surface) with pressurizations such as dressing at big Zhang Yiti or xenogenesis skin, perhaps directly uses a Farrow greatly without cutting, acquisition Farrow skin prosoma organization directly uses or preserves standby.
Farrow skin prosoma organization provided by the invention, not only can directly use in the back of drawing materials, can also be through the CTLA4/Ig (fusion gene of relevant anti-4 extracellular regions of cytotoxic T lymphocyte and human normal immunoglobulin's molecule I gG Fc section, J-Immunol, 1993,151 (5): 2453-61), CD40 (leukocyte differentiation antigen 40, transmit costimulatory signal by CD40L), CD40/Ig (the fusion gene of CD40 extracellular region and IgG Fc section, PNAS, USA, 1992,89 (14): 6550-4), CD40L (ligand molecular of CD40), PD1 (programmed death molecule 1, activated T, the inhibition receptor of expressing on the B cell, Genomics, 1994,23 (3): 704-6), OX40 (has another name called CD134, mainly is expressed on the T cell, transmit costimulatory signal by OX40L, EMBO-J, 1990,9 (4): 1063-8) wait gene or its protein product directly or indirectly to modify the back and use; After modifying, said gene, fusion gene or corresponding proteins, fusion rotein be applied to the reparation of skin wound again, do not change its oriented growth, grow and to be the characteristic of ripe skin histology, not only still have the ability that growth promoter is complete ripe skin, and can significantly reduce the immunological rejection between itself and the host.
Farrow skin prosoma organization provided by the invention, contain gene or protein modified after Farrow skin prosoma organization not only can be after being prepared into appropriate format use immediately, can also preserve the back through low temperature, ultralow temperature and use, not change its oriented growth, growth is the characteristic of ripe skin histology.Specifically be under about 4-8 ℃ low temperature, to preserve, or frozen in profound hypothermia such as liquid nitrogen.
Farrow skin prosoma organization provided by the invention, dark two degree of skin that can be widely used in due to a variety of causes such as clinical burn and scald, wound (contain dark two degree, three degree quarterings) above damaged wound surface, perhaps because radiation, the irreversible damage of autologous skin (this class wound surface need be made skin graft to promote healing, to reduce cicatrization clinically) due to the factors such as canceration.
Farrow skin prosoma organization of the present invention is being used for the use of repairing skin wound surfaces, could grow under suitable microenvironment, bud into has normal configuration and functional integrity maturation skin histology.Therefore, at first host self need provide a cleaning or relatively cleaning, aseptic or aseptic relatively microenvironment, because if microorganism is too much, especially pathogenic microorganism is too much, to directly consume Farrow skin prosoma organization, perhaps compete its nutrition, perhaps bring out the strong excessively inflammatory reaction of local microenvironment, cause not surviving of graft.Secondly, though Farrow skin prosoma organization provided by the present invention has the low characteristics of immunogenicity, but the sound individuality of normal immunity still has immunological rejection to it, especially cell-mediated immunoreation, therefore the place microenvironment that is mainly Farrow skin prosoma organization and provides will be in a low immunity or normal immune state, comprises host's self immunodeficiency and uses low-level cell immune response state in long period due to the immunoregulation means.In addition, also need the cell immune response of the microenvironment region that provides lower, comprise that variety of methods induces the longer transplantation immunity tolerance of host to Farrow.
In addition, because normal skin is an external organ, growth has a certain orientation, only with the proximate condition of normal skin growth phase under, could guarantee its not entanglement of final structure.At Farrow skin prosoma organization microgranule, cell suspension, cell mass, stamp skin and spready hide with above-mentioned preparation, transplant after the skin injury place that blood kind reason causes, also need to add one deck or multilayer coatingn at last, covering comprises various fur dead barks alive of the same race, xenogeneic, and various biologies or abiotic dressing.
The Farrow skin prosoma organization of taking from the Best Times window of the present invention, it is multi-form to be prepared into microgranule, stamp skin or cell suspension, cell mass etc., growth, bud into have the complete holostrome skin truly of epidermis, corium and the appendages of skin, and do not form teratoma in host's microenvironment that can suit after transplanting.Here the suitable microenvironment of mentioning not only comprises host's microenvironment of low immune state, also comprises host's microenvironment (gene, protein modified or combined immunization regulating measure) that immunity is sound; Farrow skin prosoma organization after the transplanting can not only play long-term flap coverage, the effect of protecting from infection, it can be grown simultaneously, bud into has corium and the sophisticated Corii Sus domestica skin of epidermis, provides abundant xenogenesis skin source to the skin injury due to reparation large tracts of land burning, the wound; And this Farrow skin can be brought into play some or all of physiological function complete, ripe skin after transplanting, and such as, mechanical strength, tenacity, comprcssive strength etc., significantly reduces the formation of cicatrix in the wound repair process, improves prognosis.
Description of drawings
Fig. 1, E42 tire pig precursor skin histology H-E dye (100 times): the cuticular cellulose of the Guizhou Fructus Foeniculi pig Farrow skin scabies soma in 42 days pregnant ages is few, and intradermal does not have obvious identifiable appendages.Holostrome skin matter is soft, crisp.
Fig. 2, E55 tire pig precursor skin histology H-E dye (100 times): the cuticular cellulose of the Guizhou Fructus Foeniculi pig Farrow skin scabies soma in 55 days pregnant ages is many than E42, and obvious identifiable appendages has appearred in intradermal, but can not confirm the kind of appendages.Holostrome skin still matter is soft, crisp.Do not see hair growth.
Fig. 3, E42 transplant 6 all back part wound surface and draw materials (substantially): subcutaneous visible porcelain white " sucker " sample neoplasm, obvious black hair follicle is arranged on it, and on " sucker ", radially distribute, the hair follicle tip is towards epidermis side.
Fig. 4, E42 transplant nude mouse after February: had obvious black wool to grow in the wound surface of healing, and had a little subcutaneous protuberance not see obvious black speck and black wool.
Fig. 5, E55 transplant nude mouse after February: existing obvious black speck and black wool grow in the wound surface of healing.
February (auricle is subcutaneous) after Fig. 6, E55 transplant: existing obvious shadow in the subcutaneous protuberance of auricle, the part black speck has appeared epidermis, but does not see that obvious black wool grows epidermis.
The specific embodiment
Embodiment 1: pregnant age E42 and E55 the obtaining and prepare of Guizhou Fructus Foeniculi pig Farrow skin prosoma organization
1, anesthesia: female Guizhou Fructus Foeniculi pig sow in accurate pregnant age (E42 and E55), 3% pentobarbital sodium: accumulated dose 1ml/kg, auricular vein gradation injection; Half amount is divided 2-3 injection first, and the about 15min of its interbody spacer takes the circumstances into consideration increase and decrease as the case may be.
2, the positive split shed in abdominal part rear portion, the about 8cm of incision length successively opens each layer, enters the abdominal cavity.
3, carefully rout up the uterus, touch uterus bump pad (the tire pig is arranged) with hands, the part is opened osculum incision uterus and is got tire, the ligation umbilical cord, and the blanket formula is sewed up the Uterus wall holostrome.
4, clean bubble tire pig with PBS, soak 10min with the normal saline that contains 0.01% bromo geramine then.
5, get Farrow:
(1) with tissue cut, tissue clamps strips the holostrome Farrow.Put into the normal saline of 0.005% bromo geramine.
(2) shred into microparticle skin with organizing to cut, size is about 1-2mm
3About.
(3) keep about 4-8 ℃ of low temperature with heat-preserving container.Prepare follow-up transplantation experiments (finishing in the 4h).
Embodiment 2: pregnant age, the BABL/c nude mouse of Guizhou Fructus Foeniculi pig Farrow skin prosoma organization of E42 and E55 was transplanted.
1, anesthesia: mice body weight 15-18g/, 1% pentobarbital sodium 0.1ml ip if revive in the art, only takes the circumstances into consideration to append 0.02ml/.(by accumulated dose 5-8 μ l/g body weight).
2, fixing: with the fixing nude mouse of aseptic medical proof fabric.
3, sterilization: iodophor disinfection nude mouse back and ears exterior feature.
4, auricle subcutaneous puncture: with 1/3 place on No. 12 lumbar puncture needle are in bilateral auricle dorsal part from distal end to the capable subcutaneous puncture of proximal part, successful diaphragm punctures, the careful inner core that promotes, No. 12 tire pig microparticle skin implantation auricles outside the lumbar puncture needle front end pin hole space are subcutaneous with being placed in advance.
5, the back is started with scalpel: 1cm * 1.5cm or 1cm * 2cm, the holostrome skin injury is to the sarolemma layer.
6, back wound surface corpse (people) skin covers: continuously or behind three of the interrupted sutures, put into microparticle skin from other one side, sew up fully; Pack or do not pack.
7, wound surface Corii Sus domestica in back covers, sewing method as above 6.Corii Sus domestica is provided by ancestor Shen, Chongqing brightness biotech firm of army.
8, the single only single cage of postoperative nude mouse is raised.
Embodiment 3: back growing state (record wound surface and the subcutaneous variation substantially of auricle) is transplanted in observation.
1, E42 post-transplantation back wound surface changes.The Farrow skin prosoma organization post-transplantation of E42, nude mouse back wound surface is covered by allograft skin, and allograft skin is the meeting blackening within a week, can accompany vesicle etc., and all backs allograft skin is total necrosis almost, forms dry crusts and is attached at wound surface; In 3-4 week, some subcutaneous protuberances appear in the dry crusts of allograft skin and normal skin intersection in succession, and quantity is few, and is not obvious, and the top layer normal skin covers, and can slide with skin; In 4-5 week, protuberance further increases, and number increases, and obviously as seen, protuberance matter is real, is similar round, and the back that protrudes in the form of annular discs sees through the visible subcutaneous shadow of epidermis, by indistinctly to obvious as seen; 5-6 week, the protuberance continued growth, subcutaneous shadow partial penetration top layer skin forms dark brown or black splotch (stricture of vagina), and has a small amount of black hair to grow on black speck.After 6 weeks, black speck and black wool continue to increase, and black speck is expanded, and merge mutually and form bigger speckle, and black wool quantity increases, and one-tenth is scooped up or scattered growth, and length increases.From 4 weeks, just come off from wound surface with the downright bad skin of the allosome of transplanting.
2, E55 post-transplantation back wound surface changes.The Farrow skin prosoma organization post-transplantation of E55, nude mouse back wound surface is covered by allograft skin, and allograft skin is the meeting blackening within a week, can accompany vesicle etc., and all backs allograft skin is total necrosis almost, forms dry crusts and is attached at wound surface; In 2-3 week, some subcutaneous protuberances appear in the dry crusts of allograft skin and normal skin intersection in succession, and quantity is few, and is not obvious, and the top layer normal skin covers, and can slide with skin; In 3-4 week, protuberance further increases, and number increases, and obviously as seen, protuberance matter is real, is similar round, and the back that protrudes in the form of annular discs sees through the visible subcutaneous shadow of epidermis, by indistinctly to obvious as seen; 4-5 week, the protuberance continued growth, subcutaneous shadow partial penetration top layer skin forms dark brown or black splotch (stricture of vagina), and has a small amount of black hair to grow on black speck.After 5 weeks, black speck and black wool continue to increase, and black speck is expanded, and merge mutually and form bigger speckle, and black wool quantity increases, and one-tenth is scooped up or scattered growth, and length increases.From postoperative 15 days, just come off from wound surface with downright bad allograft skin.
3, E42 Farrow skin prosoma organization is transplanted the subcutaneous back of auricle situation of change.In 1 week behind the auricle subcutaneous transplantation, outward appearance does not have significant change; 2-3 week, the visible subcutaneous pale red subcutaneous mass (bladder) that occurs of auricle; In 4-5 week, enclosed mass further increases, and the visible indistinctly brown or black point of part is embedded among the pale red subcutaneous mass; 5-6 week is almost replaced by black spots in the subcutaneous bladder of auricle entirely, but do not see that obvious black speck appears the skin of pinna surface this moment.After 6 weeks, there is black spots to appear skin in succession, do not see obvious black hair.In 6 thoughtful February, subcutaneous bladder size variation of auricle is not obvious during this, and change color is obvious, and naked eyes are not seen black wool.
4, E55 Farrow skin prosoma organization is transplanted the subcutaneous back of auricle situation of change.In 1 week behind the auricle subcutaneous transplantation, outward appearance does not have significant change; 2-3 week, the visible subcutaneous pale red subcutaneous mass (bladder) that occurs of auricle; In 3-4 week, enclosed mass further increases, and the visible indistinctly brown or black point of part is embedded among the pale red subcutaneous mass; 4-5 week is almost replaced by black spots in the subcutaneous bladder of auricle entirely, but do not see that obvious black speck appears the skin of pinna surface this moment.After 6 weeks, there is black spots to appear skin in succession, do not see obvious black hair.In 6 thoughtful February, subcutaneous bladder size variation of auricle is not obvious during this, and change color is obvious, and naked eyes are not seen black wool.
5, tissue slice conventional H-E dyeing tissues observed structure.
The above results shows that under suitable microenvironment (low immunity, cleaning and cytokine), the Farrow skin prosoma organization in certain pregnant age can be grown, the sophisticated pig skin tissue of appendages such as bud into has hair follicle, pigment.
Embodiment 4: the preparation of the Farrow skin prosoma organization of genetic modification
1, preparation contain CTLA4/Ig or (with) recombinant adenoviral vector (being adenovirus particles) of CD40/Ig fusion gene: pAdeasy-CTLA4/Ig, pAdeasy-CD40/Ig, pAdeasy-CTLA4/Ig-IRES2-CD40/Ig.Here mentioned CTLA4/Ig and CD40/Ig are meant that the Fc section coding region sequence of CTLA4, CD40 extracellular region coded sequence and human normal immunoglobulin IgG merges the fusion gene that forms.Confirm all can express corresponding fusion proteins through Western-blot.Method of modifying is seen following 2-4 or 5.
2, every square metre of Farrow skin prosoma organization (cell suspension, cell mass etc. are by area before preparing) is 10 with 1.0 liters of titres
8The above-mentioned adenovirus infection of PFU/ml, (pH7.2 contains glutamine 0.29g/L, Hepes1.5g/L, refining NaHCO to virus with serum-free DMEM dilution
31.6g/L).
3, infectious condition is 37 ℃, 2h.
4, metainfective Farrow skin prosoma organization can use immediately or cryopreservation standby.
5 or will Farrow skin prosoma organization directly transplanting or preserve the back and transplant, on covering, smear the carbomer frost 0.4g/cm that contains recombinant adenovirus immediately by the wound surface area
2, the about 2.0mm of thickness.The concrete preparation method of carbomer frost is: take by weighing the medical cream base carbomer of 0.48g and pack in the 50ml plastic centrifuge tube, use
60Behind the Co radiosterilization, add 1 * 10
9PFU/ml recombinant adenovirus venom 40ml, the vortex mixer mixing, and transfer to pH7.0 with 1mol/L Tris (pH9.0); Be stored in 4 ℃ standby.
The preparation of the Farrow skin prosoma organization that embodiment 5:CTLA4 protein extracellular is modified
1, the CTLA4 extracellular region protein obtains.(Yi Shaoxuan, Wu Jun. etc., the screening of the structure of people CTLA-4 extracellular region cDNA yeast expression vector and high copy stable integration bacterial strain. Chongqing medical science, 2002,31 (8): 679-681).
2, the CTLA4 extracellular region protein (1.0 μ g/ μ l) with above-mentioned preparation mixes (1.0-2.0 μ g/10 with the cell suspension of Farrow skin tissue
6Cell), directly be applied on the wound surface, stick in wound surface after perhaps immersing gel sponge, biological, abiotic dressing such as reuse allograft skin or xenogenesis skin covers on it.
Embodiment 6: the preservation of Farrow skin prosoma organization
1, after drawing materials (through or not modified) Farrow prosoma organization (cell suspension, cell mass, microparticle skin, stamp skin etc.) can be stored in 4-8 ℃ of refrigerator standby (2-3d).Perhaps frozen as follows.
2,4 ℃ of freeze proof 30min; Anti frozen liquid: 20%DMSO, 6% propylene glycol, basal liquid are PBS (pH7.2).
3, the direct liquid nitrogen cryopreservation in freeze proof back can recover the vigor more than 70% behind the rewarming.
Embodiment 7: Farrow skin prosoma organization combined immunization regulator transplantation immunity perfects mice
1, the sound SPF level BABL/c mice of immunity, preserved skin, the back prepares the holostrome skin injury, and (about 1.0 * 2.0cm), Farrow skin precursor microgranule is transplanted, and people's cadaver skin covers, and sews up.
2, CTLA4-Ig fusion rotein associating anti-CD 40 L monoclonal antibody tail vein injection: CTLA4-Ig dosage is 200 μ g/ Mus, and the dosage of CD40L monoclonal antibody (MR1) is 250 μ g/ Mus; Be respectively the 0d after the transplanting inject time, 2d, 4d, 6d, 14d, 28d (per two weeks injection once after 14 days).Matched group is injecting normal saline only.
3, the immunity of observation use in conjunction immunomodulator perfects the growth promoter situation of the Farrow skin prosoma organization of mouse back wound surface.
(1) on average to survive be 10 ± 3 days to the graft of matched group (immunity perfects mice and transplants not modified Farrow), and massive inflammatory cells infiltrated is arranged.Almost all be ostracised in 2 weeks.
(2) the processed group graft can long-term surviving, and can the same growth promoter with the Farrow that migrates to nude mouse for having black hair and melanic pig skin tissue.A small amount of inflammatory cell infiltration is also arranged, but significantly reduce than matched group.
The above results explanation use in conjunction immunomodulating means, Farrow skin prosoma organization can the control environment after transplanting in growth promoter be complete, sophisticated skin histology.
Claims (3)
1. a Farrow skin prosoma organization that is used for repairing skin wound surfaces is characterized in that described Farrow skin prosoma organization derives from the tire pig of inbred line, closed colony or the Hybrid of all pig kinds, the pregnant age of tire pig be 21 days to going out the birthday; Described Farrow skin prosoma organization adopts the Farrow skin prosoma organization through genetic modification; The Farrow skin prosoma organization of described genetic modification comprise protein CTL A4/Ig, CD40, CD40/Ig, CD40L, PD1 or OX40 with and derived fusion proteins and the corresponding gene of these albumen directly or the Farrow skin prosoma organization that obtains by carrier modification.
2. Farrow skin prosoma organization according to claim 1 is characterized in that: described pig kind is Guizhou pig, crust horse pig or Rongchang County pig.
3. Farrow skin prosoma organization according to claim 2 is characterized in that: described pig kind is Guizhou Fructus Foeniculi pig or crust horse Fructus Foeniculi pig.
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| CN1397355A (en) * | 2002-08-14 | 2003-02-19 | 苏州大学 | Material for repairing defective tissue of body and its preparing process |
| CN1504241A (en) * | 2002-12-04 | 2004-06-16 | 曹谊林 | Tissue engineering artificial skin constructed on the rack of heterogenous or xenogenous bone matrix gelatin |
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| CN1397355A (en) * | 2002-08-14 | 2003-02-19 | 苏州大学 | Material for repairing defective tissue of body and its preparing process |
| CN1504241A (en) * | 2002-12-04 | 2004-06-16 | 曹谊林 | Tissue engineering artificial skin constructed on the rack of heterogenous or xenogenous bone matrix gelatin |
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