CN103083667A - Continuous dosage scheme of olfactory ensheathing cell proliferation reagent - Google Patents
Continuous dosage scheme of olfactory ensheathing cell proliferation reagent Download PDFInfo
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- CN103083667A CN103083667A CN201110337608XA CN201110337608A CN103083667A CN 103083667 A CN103083667 A CN 103083667A CN 201110337608X A CN201110337608X A CN 201110337608XA CN 201110337608 A CN201110337608 A CN 201110337608A CN 103083667 A CN103083667 A CN 103083667A
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Abstract
The invention provides an effective dosage scheme of an olfactory ensheathing cell proliferation reagent, a kit containing the olfactory ensheathing cell proliferation reagent, and a use of the kit. The scheme opposite to a short-period high-dosage dosage scheme is characterized in that the olfactory ensheathing cell proliferation reagent, such as human chorionic gonadotrophin (HCG), lactogen and the like, is continuously delivered to a mammal subject in a low dosage manner for several days.
Description
Technical field
The invention belongs to field of tissue engineering technology, particularly, relate to a kind of test kit of Olfactory bulb cell propagation, the application of this test kit and medication that promotes Olfactory bulb cell propagation of promoting.
Background technology
The exploitation of smelling the technology of the separation of sheath and In vitro culture pluripotency Olfactory essheathing cell (olfactory ensheathing cells, OECs) has significantly changed the treatment prospect of nervous system disease and disease.Have been found that fetal brain can be used for separating and In vitro culture pluripotency Olfactory essheathing cell.No matter be from fetus or adult brain, OECs has the characteristic of central nervous system's (CNS) astrocyte and periphery Xue Wangshi cell, OCEs after transplanting can move in the myeloid tissue of host's damage, can guide the neurite of supporting damage to regenerate, grow, extend.But also can make it carry the allogenic gene that some promotes neuron regeneration by transgenic technology, express the molecule of some short neuranagenesis, thereby improve the internal medium of nerve injury, induce the spinal neuron regeneration of damage, make the potentiality of impaired spinal cord regeneration be brought into play, reach the purpose of spinal cord regeneration and functional rehabilitation.The source that these find not only to provide the neurocyte that can be used for transplanting has also confirmed the existence of pluripotency neural stem cell in the adult brain and has generated the probability of neurons or neurogliocyte from these stem cell original positions.
Olfactory essheathing cell propagation reagent comprises can increase any material of mammal Olfactory essheathing cell quantity in external or body.Promotion reagent used herein has identical meanings with propagation reagent.The reagent that can increase Olfactory essheathing cell quantity comprises:
1) follicle stimulating hormone (FSH): can combine with the effect of LH (interstitialcellstimulating hormone (ICSH)), and induce the LH expression of receptor, thereby strengthen the effect of LH signal conduction.
2) human chorionic gonadotropin (HCG): be that it is comprised of α and the dimeric glycoprotein of β by a kind of glycoprotein of the trophoblastic cell secretion of Placenta Hominis, but irritating smell sheath cell propagation.
3) growth hormone (GH): but irritating smell sheath cell propagation.
4) insulin-like growth factor (IGFs) (comprising IGF-1): can with GH coordinative role, and irritating smell sheath cell propagation.
5) growth hormone releasing hormone (GHRH): by the hypothalamus secretion, and induce GH to discharge from antepituitary, cause the increase of GH cyclical level.
6) prolactin antagonist (PRL): secretion and promotion Olfactory essheathing cell propagation from antepituitary.
7) Prolactin-Releasing Peptide (PRP): can cause the release of prolactin antagonist.
8) fibroblast growth factor (FGF): promote the mitotic reagent of Olfactory essheathing cell.
9) estrogen: the propagation that promotes Olfactory essheathing cell.
10) serotonin: the propagation that promotes neural stem cell in Hippocampus.
11) epidermal growth factor: the mitogenesis reagent of neural stem cell.
Summary of the invention
The Olfactory essheathing cell propagation and the differentiation agents that are used for the treatment of nervous system disease do not ratified clinically at present.These reagent are useful for treatment nervous system disease and disease, thereby effective dosage regimen of utilizing these reagent need to be arranged.The invention provides effective dosage regimen of using Olfactory essheathing cell propagation reagent, comprise the test kit of implementing the effective dosage regimen of Olfactory essheathing cell propagation reagent and and uses thereof.Particularly, with opposite with the high dose administration in a short time, low dosage is bred reagent with Olfactory essheathing cell and is delivered to mammalian subject in a continuous manner.
The object of the present invention is to provide effective dosage regimen and the purposes of Olfactory essheathing cell propagation test kit, its reagent.Especially, high dose reagent is opposite with giving in a short time, and Olfactory essheathing cell propagation reagent is delivered to mammalian subject in continuous low dosage mode.But the compositions of described reagent and method short-term or life-time service.
Accordingly, the invention provides the Olfactory essheathing cell propagation reagent of optimization effective dose, and the method and the test kit that effectively increase Olfactory essheathing cell quantity in mammal, comprise and Olfactory essheathing cell is bred reagent give continuously mammal a period of time.By selecting test kit, the accumulated dose of the Olfactory essheathing cell propagation reagent that gives within described period equals effective dose, and wherein said medicine-feeding period is at least three days.
Method and the test kit of neurodegenerative disease or disease in this further provides treatment or has improved mammal.Described method comprises by optional this test kit that uses, and the Olfactory essheathing cell of effective dose is bred reagent give continuously mammal one period, and wherein said medicine-feeding period is at least three days.
Description of drawings
Fig. 1 is that the subcutaneous injection prolactin antagonist promotes the Olfactory essheathing cell proliferation experiment
Fig. 2 is that the subcutaneous injection human chorionic gonadotropin promotes the Olfactory essheathing cell proliferation experiment
The specific embodiment
Embodiment 1
Test kit described in the invention can further be provided for the proliferation and differentiation reagent of the optimal dose of whole treatment phase, and the proliferation and differentiation reagent accumulated dose that wherein gives within the described treatment phase equals effective dose, and the wherein said treatment phase is at least three days.
Any method administration that Olfactory essheathing cell propagation reagent can have been set up by this area, for example, by in intravenous, intra-arterial, colonic, trachea, in intraperitoneal, intranasal, blood vessel, intracranial, subcutaneous, intramuscular, topical or its combination in any.The drug delivery device or its element that are used for administration can be included in the test kit that has comprised Olfactory essheathing cell propagation reagent.
In male rat with the concentration h inf prolactin antagonist that is equivalent to 10～20 times of Intraventricular prolactin antagonist six days.Fig. 1 has showed the total amount from bromodeoxyribouridine positive cell in the chamber inferior segment (SVZ) of 8 sections of every animal.Observed the optimal growth in SVZ Olfactory essheathing cell propagation level with 15 times of meterings the time.Significance with respect to contrast: 10 *=* p＜0.05; 15 *=* p＜0.01; 20 *=* p＜0.05; For condition n=3 used; Carry out single factor variance with Turkey posthoc test and divide plate.
Fig. 2 has showed that the subcutaneous injection human chorionic gonadotropin can promote Olfactory essheathing cell propagation.When the HCG that uses respectively 100ug and 330ug concentration carried out 6 days h infs, the propagation of the Olfactory essheathing cell in SVZ will be far longer than the RSA contrast.
Claims (5)
1. offer the method for the Olfactory essheathing cell propagation reagent of mammal effective dose, be included in and give continuously mammal Olfactory essheathing cell propagation reagent in the first treatment phase, the Olfactory essheathing cell propagation reagent accumulated dose that wherein gives within described the first treatment phase equals effective dose, and wherein said the first treatment phase is at least three days.
2. method according to claim 1, wherein the persistent period of the first treatment phase be selected from least four days, at least five days, at least six days, at least seven days and fortnight at least.
3. method according to claim 1, further be included in and give continuously mammal Olfactory essheathing cell propagation reagent in the second treatment phase, and wherein the second treatment phase was opened in after the first treatment phase finished, and the cycle is at least three days.
4. according to claim 1,2,3 described methods, wherein Olfactory essheathing cell propagation reagent is by the every day of subcutaneous injection administration at least one times.
5. according to claim 1,2,3 described methods, wherein Olfactory essheathing cell propagation reagent is not by the infusion administration.
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| CN201110337608XA CN103083667A (en) | 2011-11-01 | 2011-11-01 | Continuous dosage scheme of olfactory ensheathing cell proliferation reagent |
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Citations (5)
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| WO2005097184A2 (en) * | 2004-03-26 | 2005-10-20 | Human Genome Sciences, Inc. | Antibodies against nogo receptor |
| CN1759888A (en) * | 2004-10-13 | 2006-04-19 | 中山大学 | Application scheme for treating injury of spinal cord by transplanting Olfactory essheathing cells |
| CN101405021A (en) * | 2006-03-17 | 2009-04-08 | 干细胞治疗公司 | Continuous dosing regimens for neural stem cell proliferating agents and neural stem cell differentiating agents |
| CN101460621A (en) * | 2006-06-07 | 2009-06-17 | 建新公司 | Gene therapy for amyotrophic lateral sclerosis and other spinal cord disorders |
| CN101591641A (en) * | 2008-05-30 | 2009-12-02 | 北京市虹天济神经科学研究院 | The Olfactory essheathing cell culture supernatant is induced the Olfactory stem cell differentiation method |
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2011
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005097184A2 (en) * | 2004-03-26 | 2005-10-20 | Human Genome Sciences, Inc. | Antibodies against nogo receptor |
| CN1759888A (en) * | 2004-10-13 | 2006-04-19 | 中山大学 | Application scheme for treating injury of spinal cord by transplanting Olfactory essheathing cells |
| CN101405021A (en) * | 2006-03-17 | 2009-04-08 | 干细胞治疗公司 | Continuous dosing regimens for neural stem cell proliferating agents and neural stem cell differentiating agents |
| CN101460621A (en) * | 2006-06-07 | 2009-06-17 | 建新公司 | Gene therapy for amyotrophic lateral sclerosis and other spinal cord disorders |
| CN101591641A (en) * | 2008-05-30 | 2009-12-02 | 北京市虹天济神经科学研究院 | The Olfactory essheathing cell culture supernatant is induced the Olfactory stem cell differentiation method |
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| 李升等: "嗅鞘细胞对神经干细胞增殖与分化的影响", 《神经解剖学杂志》 * |
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Addressee: Beijing QMLC Stem Cell Technology Co., Ltd. Document name: Notification of Publication and of Entering the Substantive Examination Stage of the Application for Invention |
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Address after: 100084, C building, Tsinghua Science and technology building, No. 1 Zhongguancun East Road, Beijing, Haidian District, 301 Applicant after: Beijing QMLC Stem Cell Technology Co., Ltd. Address before: 100097 Beijing city Haidian District minzhuang Road No. 3, Tsinghua Science Park building 204 Yuquan Huigu 7 Applicant before: Beijing QMLC Stem Cell Technology Co., Ltd. |
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Application publication date: 20130508 |