CN105709278A - Tissue engineering spinal marrow containing directional axons in various areas - Google Patents
Tissue engineering spinal marrow containing directional axons in various areas Download PDFInfo
- Publication number
- CN105709278A CN105709278A CN201510224166.6A CN201510224166A CN105709278A CN 105709278 A CN105709278 A CN 105709278A CN 201510224166 A CN201510224166 A CN 201510224166A CN 105709278 A CN105709278 A CN 105709278A
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- Prior art keywords
- tissue engineering
- axons
- nerve cells
- spinal cord
- neurocyte
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Links
- 210000003050 axon Anatomy 0.000 title abstract description 11
- 239000000463 material Substances 0.000 claims abstract description 33
- 230000004009 axon guidance Effects 0.000 claims abstract description 12
- 239000002356 single layer Substances 0.000 claims abstract description 5
- 230000001174 ascending effect Effects 0.000 claims abstract 3
- 210000000278 spinal cord Anatomy 0.000 claims description 20
- 210000004027 cell Anatomy 0.000 claims description 13
- 239000000835 fiber Substances 0.000 claims description 3
- 210000004885 white matter Anatomy 0.000 claims description 3
- 210000004884 grey matter Anatomy 0.000 claims description 2
- 239000012141 concentrate Substances 0.000 claims 2
- 102000004127 Cytokines Human genes 0.000 claims 1
- 108090000695 Cytokines Proteins 0.000 claims 1
- 230000008520 organization Effects 0.000 claims 1
- 210000002569 neuron Anatomy 0.000 abstract description 14
- 239000010410 layer Substances 0.000 abstract description 6
- 238000011084 recovery Methods 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract 2
- 230000007830 nerve conduction Effects 0.000 abstract 1
- 230000008054 signal transmission Effects 0.000 abstract 1
- 210000001519 tissue Anatomy 0.000 description 9
- 208000020431 spinal cord injury Diseases 0.000 description 7
- 210000005036 nerve Anatomy 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 238000004088 simulation Methods 0.000 description 4
- 108010082117 matrigel Proteins 0.000 description 3
- 230000000694 effects Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 210000002804 pyramidal tract Anatomy 0.000 description 2
- 230000008929 regeneration Effects 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 1
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 1
- 108090000368 Fibroblast growth factor 8 Proteins 0.000 description 1
- 102100037680 Fibroblast growth factor 8 Human genes 0.000 description 1
- 102000009065 Netrin-1 Human genes 0.000 description 1
- 108010074223 Netrin-1 Proteins 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000005056 cell body Anatomy 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 239000012531 culture fluid Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000002161 motor neuron Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 210000003009 spinothalamic tract Anatomy 0.000 description 1
- 230000001228 trophic effect Effects 0.000 description 1
- 230000010415 tropism Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
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- Prostheses (AREA)
Abstract
The invention discloses tissue engineering spinal marrow containing directional axons in various areas. By controlling the directions of axons growing from nerve cells in a stent material in accordance with the areas, the neuron changing time of the nerve cells in the stent material can be greatly reduced. In an ascending area, nerve cells area are distributed on the bottom of the stent layer in a monolayer mode, and substances, which are adsorbed with axon guidance factors, are arranged on the top of the stent material; in a descending area, nerve cells area are distributed on the top of the stent layer in a monolayer mode, and substances, which are adsorbed with axon guidance factors, are arranged on the bottom of the stent material. Through cultivation, axons can grow from the nerve cells in the ascending area upwards, while axons can grow from the nerve cells in the descending area downwards. Therefore, the tissue engineering spinal marrow disclosed by the invention can simulate the directivity of a nerve conduction path under a physiological status and can complete the connection and the repair of transected spinal marrow with relatively less neuron changing times, so that the stability and the accuracy of signal transmission after the transplanted tissue engineering spinal marrow is integrated with host spiral marrow are guaranteed, and the recovery of spinal marrow functions is promoted.
Description
Art:
The present invention relates to a kind of tissue engineering spinal cord for repairing spinal cord injury, especially contain the tissue engineering spinal cord of upstream or downstream aixs cylinder according to zones of different.
Background technology:
Neurocyte/neuron belongs to permanent cell, lacks regeneration capacity, therefore spinal cord injury, and especially the patient of spinal cord transection wound is difficult to recover normal spinal function voluntarily.In repair of spinal cord injury research field, people attempt building artificial spinal cord rack material composite nerve trophic factors and seed cell to repair spinal cord injury, its ultimate principle is: the man-made support material of transplanting can provide, for the cell that spinal cord reparation is relevant, the growing environment being suitable for, promote the Growth and Differentiation of seed cell (it is crucial that neurocyte) in timbering material and the regeneration of host's spinal cord broken ends of fractured bone neuron axon, reconnect by upper and lower for host's lesion level neutral net with the effect of similar relay station.
Neuron is the cell of a kind of polarization, and form is mainly made up of cell space (including dendron) and the root length aixs cylinder sent by cell space.Nervous pathway in spinal cord to experience and once to arrive neuron for several times and change unit under normal circumstances, when changing unit, upper neuronic aixs cylinder is connected with cell space or the dendron of lower motor neuron, change the neuron axon after unit with change unit before neuron axon on direction, keep consistent.
But, through consulting patent and the bibliographical information of all kinds of man-made support material relevant with repair of spinal cord injury, even if we have found that existing timbering material partition type tissue engineering spinal cord is also simply provided with longitudinal duct in the distributed areas of uplink and downlink nerve fibre bundle, and the direction of the sent aixs cylinder of neurocyte in uncontrollable conduit, namely the neurocyte in longitudinal duct random up or down can grow aixs cylinder.The aixs cylinder grown up sent such as neurocyte in conduit is likely to be connected with the descending nerve cell axons of host, and this connected mode can not exercise its normal function.And owing to the neurocyte of plantation is uniformly distributed in whole three-dimensional bracket material, this can cause that uplink and downlink Nervous pathway repeatedly changes unit in timbering material and aixs cylinder directivity erroneous matching occurs, making nerve signal effectively not conduct, repairing effect is had a greatly reduced quality.
Summary of the invention:
In order to overcome the randomness in the direction of growth of nerve cell axons in existing tissue engineering spinal cord and neurocyte to change the deficiency that unit's number of times is too much, the invention provides a kind of novel tissue engineering spinal cord, this tissue engineering spinal cord can by the direction of the sent aixs cylinder of Region control neurocyte, and can greatly reduce neurocyte in material change unit number of times.
The technical solution adopted for the present invention to solve the technical problems is: according to aixs cylinder trend, timbering material is marked off up region and descender region.In descender, neurocyte will be planted in the upper end of timbering material, and the neurocyte in the up district of aixs cylinder will be planted in the lower end of timbering material.We can insert the material of slow release axon guidance cue (such as FGF-2, FGF-8, netrin-1 etc.) at the material other end relative with cell simultaneously, and the aixs cylinder that inducing nerve cell sends grows towards the direction at axon guidance cue place.In vitro culture a period of time, until neurocyte after timbering material interior orientation grows the aixs cylinder of certain length, this timbering material containing directed aixs cylinder is transplanted in the organism of spinal cord injury by again.In host's nerve cell axons grows into our timbering material, growth without experiencing distance can be set up with the neurosome being positioned at material upper end or lower end or dendron and is connected, and changing the neurocyte after unit in material can be connected with host subordinate Neuronal soma or dendron foundation with same tropism's aixs cylinder.Thus we can effectively by uplink and downlink nervous pathway according to direction UNICOM again originally, reach to repair the purpose of spinal cord injury.
The invention has the beneficial effects as follows: the directivity of simulation physiological status Nervous pathway, and change unit's number of times with less neurocyte and complete the connection reparation of cross-section spinal cord.Thus the stability that after ensureing the tissue engineering material transplanted and the integration of host's spinal cord, nerve signal transmits and accuracy, promote the recovery of spinal function.
Accompanying drawing illustrates:
Below in conjunction with drawings and Examples, the present invention is further described.
Fig. 1 is single longitudinal duct and the internal structure ideograph thereof of the present invention.
Fig. 2 is the cross section ideograph of one embodiment of the present of invention.
Fig. 3 is the I--I sectional view of Fig. 2.
Detailed description of the invention:
In FIG, neurocyte (1) is planted in one end of conduit (4), material (3) containing axon guidance cue is present in the other end of conduit (4), in vitro in incubation, cell space (1) the direction oriented growth that the aixs cylinder (2) sent can exist towards axon guidance cue.For ensureing that axon guidance cue forms the Concentraton gradient successively decreased to cell space end in conduit, the material (3) containing axon guidance cue is preferably selected slow-release material (in the present embodiment, we select gelfoam).
In the embodiment depicted in figure 2, tissue engineering spinal cord timbering material marks the scope (9) of grey matter according to corresponding segments of spinal cord, and white matter part comprises the big interval of uplink and downlink two, wherein up district and descender can be segmented as required further, in the present embodiment, up district is further divided into the rear up district (5) of simulation fasciculus gracilis cuneate fascicle and simulates the up district, side (6) of spinothalamic tract by us, and descender is further divided into the front descender (8) of simulation anterior corticospinal tract and the descender, side (8) of simulation lateral corticospinal tract.
Embodiment shown in Fig. 3 illustrates the I--I sectional view of Fig. 2, many longitudinal ducts (16) are comprised in rear up district (5) and front descender (8), first neurocyte is laid in the upper cultivation of spawn (matrigel) of thin layer by us, after cell attachment is stable, matrigel layer (12) containing monolayer neuronal cell is taken off gently, covering is packed in the bottom in rear up district (5), and the gelfoam floor (10) containing axon guidance cue covers the top in up district (5) after being packed in simultaneously.And in front descender (8), the matrigel layer (13) containing monolayer neuronal cell covers and is packed in its top, the gelfoam layer (11) containing axon guidance cue covers and is packed in bottom it.Timbering material is laterally statically placed in culture fluid and cultivates a period of time (4-7 days), after being positioned at, the neurocyte of bottom, up district (5) upwards grows aixs cylinder (14), and the neurocyte at front descender (8) top grows downwards aixs cylinder.
Claims (4)
1. subregional organization's engineering spinal cord, it is made up of bioavailability bracket material, cytokine and the seed cell being planted in timbering material, and it is divided into white matter and grey matter district, in white matter district, the form scope according to Ascending Fiber bundle and Descending fibers bundle arranges longitudinal duct.It is characterized in that: up district and comprise the directed aixs cylinder sent by neurocyte in the longitudinal duct of descender.
2. tissue engineering spinal cord according to claim 1, is characterized in that the neurocyte in up district concentrates on the bottom of conduit, and the material being adsorbed with axon guidance cue is placed in the top of conduit.
3. tissue engineering spinal cord according to claim 1, is characterized in that the neurocyte of descender concentrates on the top of conduit, and the material being adsorbed with axon guidance cue is placed in the bottom of conduit.
4. tissue engineering spinal cord according to claim 1, is characterized in that the neurocyte in material uplink and downlink district is monolayer arrangement.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510224166.6A CN105709278B (en) | 2015-05-06 | 2015-05-06 | Contain the tissue engineering spinal cord of orientation aixs cylinder in subregion |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510224166.6A CN105709278B (en) | 2015-05-06 | 2015-05-06 | Contain the tissue engineering spinal cord of orientation aixs cylinder in subregion |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105709278A true CN105709278A (en) | 2016-06-29 |
| CN105709278B CN105709278B (en) | 2019-05-21 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510224166.6A Active CN105709278B (en) | 2015-05-06 | 2015-05-06 | Contain the tissue engineering spinal cord of orientation aixs cylinder in subregion |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101278865A (en) * | 2008-05-09 | 2008-10-08 | 南通大学 | Partition type tissue engineering spinal cord |
| CN101766836A (en) * | 2009-01-21 | 2010-07-07 | 丁坦 | Preparation method of nano silver cordspinal cord and peripheral nerve repairing material |
| US20100291180A1 (en) * | 2007-02-20 | 2010-11-18 | Uhrich Kathryn E | Nerve guidance tubes |
-
2015
- 2015-05-06 CN CN201510224166.6A patent/CN105709278B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100291180A1 (en) * | 2007-02-20 | 2010-11-18 | Uhrich Kathryn E | Nerve guidance tubes |
| CN101278865A (en) * | 2008-05-09 | 2008-10-08 | 南通大学 | Partition type tissue engineering spinal cord |
| CN101766836A (en) * | 2009-01-21 | 2010-07-07 | 丁坦 | Preparation method of nano silver cordspinal cord and peripheral nerve repairing material |
Non-Patent Citations (2)
| Title |
|---|
| DANIEL J. MACAYA等: ""Astrocyte infiltration into injectable collagen-based hydrogels containing FGF-2 to treat spinal cord injury"", 《BIOMATERIALS》 * |
| 邵阳 等: ""组织工程支架及其修复技术在脊髓损伤中的应用"", 《中国组织工程研究与临床康复》 * |
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| Publication number | Publication date |
|---|---|
| CN105709278B (en) | 2019-05-21 |
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Effective date of registration: 20190408 Address after: 20101 No. 2880 Qiju Road, Minhang District, Shanghai Applicant after: Shanghai Blue Cross Brain Hospital Co., Ltd. Address before: 45 000 1 Liuyuan 15, No. 100 Science Avenue, Zhengzhou High-tech Zone, Henan Province Applicant before: Zhou Han |
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Effective date of registration: 20200615 Address after: Room 158, floor 14, building 2, No. 588, Zixing Road, Minhang District, Shanghai 200000 Patentee after: Shanghai Lansheng brain medical research Co., Ltd Address before: 20101 No. 2880 Qiju Road, Minhang District, Shanghai Patentee before: Shanghai Blue Cross Brain Hospital Co.,Ltd. |
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