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CN112514888A - Preparation process of cryopreservation protection solution for umbilical cord mesenchymal stem cells - Google Patents

Preparation process of cryopreservation protection solution for umbilical cord mesenchymal stem cells
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Publication number
CN112514888A
CN112514888ACN202011399412.9ACN202011399412ACN112514888ACN 112514888 ACN112514888 ACN 112514888ACN 202011399412 ACN202011399412 ACN 202011399412ACN 112514888 ACN112514888 ACN 112514888A
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umbilical cord
cells
mesenchymal stem
digestion
treatment
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CN202011399412.9A
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周自豪
强斌
廉云飞
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Jiangsu Tuohong Kangheng Pharmaceutical Co ltd
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Jiangsu Tuohong Kangheng Pharmaceutical Co ltd
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Abstract

Translated fromChinese

本发明涉及生物细胞技术领域,尤其为一种用于脐带间充质干细胞的冻存保护液制备工艺,包括以下步骤:首先将脐带组织进行剪开和铺开,然后使用消毒液对脐带组织的表面进行清理;对脐带组织进行剪碎处理,然后对剪碎之后的脐带组织内加入胰酶和EDTA进行消化处理;对酶解消化后的细胞进行离心处理然后在完全培养基重选后,进行密度传代;对液体进行离心处理;对离心得到的上清中进行加入二甲基亚砜,然后进行混合处理,再转入液氮中进行长期的保存处理,本发明中,通过上述技术工艺,不仅可以有效的避免牛血清的使用,从而尽可能少引入异源的病毒和致敏源,而且可以有效的提高脐带间充质干细胞的冻存保护液的质量。The invention relates to the technical field of biological cells, in particular to a process for preparing a cryopreservation protection solution for umbilical cord mesenchymal stem cells, comprising the following steps: firstly cutting and spreading the umbilical cord tissue, and then using a disinfectant to sterilize the umbilical cord tissue. The surface is cleaned; the umbilical cord tissue is shredded, and then trypsin and EDTA are added to the shredded umbilical cord tissue for digestion; the digested cells are centrifuged and then reselected in complete medium. Density passage; centrifuge the liquid; add dimethyl sulfoxide to the supernatant obtained by centrifugation, then carry out mixing treatment, and then transfer to liquid nitrogen for long-term storage treatment. In the present invention, through the above technical process, Not only can effectively avoid the use of bovine serum, so as to introduce as few heterologous viruses and allergens as possible, but also can effectively improve the quality of the cryopreservation solution for umbilical cord mesenchymal stem cells.

Description

Preparation process of cryopreservation protection solution for umbilical cord mesenchymal stem cells
Technical Field
The invention relates to the technical field of biological cells, in particular to a preparation process of a cryopreservation protection solution for umbilical cord mesenchymal stem cells.
Background
Mesenchymal stem cells are adult stem cells derived from mesoderm and ectoderm in early development, have high self-renewal and multi-directional differentiation potential, and are present in various connective tissues and organ mesenchyme such as bone marrow, fat and the like. Mesenchymal stem cells have become a research hotspot in the stem cell field due to the great potential in the fields of tissue engineering, hematopoietic stem cell transplantation and gene therapy. The mesenchymal stem cells from the umbilical cord have very high differentiation potential, can be directionally induced and differentiated into a plurality of tissues such as bones, cartilages, muscles, tendons, ligaments and nerves, have low immunogenicity, convenient material taking and small ethical disputes, and have wider application prospect compared with the mesenchymal stem cells from other sources such as bone marrow. The mesenchymal stem cells have the characteristic of being capable of being greatly expanded, the human umbilical cord mesenchymal stem cells can obviously age and die when being excessively subcultured, the multi-differentiation potential is reduced due to long-term in vitro culture, the adhesion capability is reduced, the cell apoptosis rate is increased, and the phenomenon that people suffer from intestinal atrophy and the like can be caused by Crohn's disease.
Disclosure of Invention
The invention aims to provide a preparation process of a cryopreservation protection solution for umbilical cord mesenchymal stem cells, so as to solve the problems in the background technology.
In order to achieve the purpose, the invention provides the following technical scheme:
a preparation process of a cryopreservation protection solution for umbilical cord mesenchymal stem cells comprises the following steps:
the method comprises the following steps: cleaning treatment: firstly, using sterilized surgical scissors to cut and spread umbilical cord tissues, fixing the spread umbilical cord tissues, then using a disinfectant to clean the surfaces of the umbilical cord tissues, using a cotton ball to dip the disinfectant to repeatedly disinfect and clean the surfaces of the umbilical cord during cleaning, wherein the disinfection and cleaning frequency is 3-5 times, then using a cell pretreatment cleaning buffer solution to clean the umbilical cord tissues, and during cleaning, using the cotton ball to dip the buffer solution to repeatedly clean the umbilical cord tissues, wherein the cleaning frequency is 3-5 times, so that the proportion of red blood cells on the umbilical cord tissues is effectively reduced, and then collecting the umbilical cord tissues for later use;
step two: and (3) digestion treatment: then, carrying out shearing treatment on the umbilical cord tissue obtained in the step one, and controlling the shearing size of the umbilical cord tissue during the shearing treatment so that the area of the upper end surface of a single umbilical cord tissue is controlled to be 0.08cm2-0.2cm2Adding pancreatin and EDTA into the minced umbilical cord tissue for digestion treatment, wherein during the digestion treatment, the pancreatin and EDTA completely immerse the umbilical cord tissue, during the digestion treatment, the umbilical cord tissue is repeatedly turned over, then the umbilical cord tissue is removed after the digestion treatment, then a mesenchymal stem cell culture medium is added into an enzymolysis liquid, so that the digestion is stopped, finally, the cells obtained after the enzymolysis are cleaned, and finally, a cell suspension is obtained;
step three: cell culture: centrifuging the cells subjected to enzymolysis and digestion obtained in the step two, wherein during centrifugation, the cells are centrifuged at a rotating speed of 5000-8000 rpm to ensure the rupture of the cells, and then performing density passage after complete culture medium reselection to continuously grow the cells for 24-72 h;
step four: centrifuging and taking a supernatant: centrifuging the liquid obtained in the third step, wherein the centrifugation is carried out at the rotating speed of 1500-1800 rpm for 10-15 minutes, and then taking the supernatant for later use;
step five: freezing treatment: and D, adding dimethyl sulfoxide into the supernatant obtained in the fourth step, mixing, storing at low temperature overnight after mixing, and finally transferring into liquid nitrogen for long-term storage.
Preferably, 0.02mL/cm is added to the cells in the second step20.2% pancreatin and 0.03% EDTA, and a digestion time of 20 min.
Preferably, 0.01mL/cm is added to the cells in the second step20.3% pancreatin and 0.04% EDTA and digestion time 15 min.
Preferably, 0.03mL/cm is added to the cells in the second step20.1% pancreatin and 0.02% EDTA, and a digestion time of 25 min.
Preferably, the ratio of 5000 cells/cm in step three28000 cells/cm2The passage density of (2) is subjected to passage.
Compared with the prior art, the invention has the beneficial effects that:
according to the invention, by the technical process, the use of bovine serum can be effectively avoided, so that heterologous viruses and sensitization sources are introduced as little as possible, and the quality of the cryopreservation protection solution for the umbilical cord mesenchymal stem cells can be effectively improved.
Detailed Description
Example 1: the invention provides a technical scheme that:
a preparation process of a cryopreservation protection solution for umbilical cord mesenchymal stem cells comprises the following steps:
the method comprises the following steps: cleaning treatment: firstly, using sterilized surgical scissors to cut and spread umbilical cord tissues, fixing the spread umbilical cord tissues, then using a disinfectant to clean the surfaces of the umbilical cord tissues, using a cotton ball to dip the disinfectant to repeatedly disinfect and clean the surfaces of the umbilical cord during cleaning, wherein the disinfection and cleaning frequency is 3-5 times, then using a cell pretreatment cleaning buffer solution to clean the umbilical cord tissues, and during cleaning, using the cotton ball to dip the buffer solution to repeatedly clean the umbilical cord tissues, wherein the cleaning frequency is 3-5 times, so that the proportion of red blood cells on the umbilical cord tissues is effectively reduced, and then collecting the umbilical cord tissues for later use;
step two: and (3) digestion treatment: then, carrying out shearing treatment on the umbilical cord tissue obtained in the step one, and controlling the shearing size of the umbilical cord tissue during the shearing treatment so that the area of the upper end surface of a single umbilical cord tissue is controlled to be 0.08cm2-0.2cm2Then adding pancreatin and EDTA into the minced umbilical cord tissue for digestion treatment, wherein the pancreatin and EDTA completely immerse the umbilical cord tissue during the digestion treatment, repeatedly turning over the umbilical cord tissue during the digestion treatment, removing the umbilical cord tissue after the digestion treatment, then adding a mesenchymal stem cell culture medium into an enzymolysis solution,thereby terminating digestion, and finally cleaning cells obtained after enzymolysis to finally obtain cell suspension;
step three: cell culture: centrifuging the cells subjected to enzymolysis and digestion obtained in the step two, wherein during centrifugation, the cells are centrifuged at a rotating speed of 5000-8000 rpm to ensure the rupture of the cells, and then performing density passage after complete culture medium reselection to continuously grow the cells for 24-72 h;
step four: centrifuging and taking a supernatant: centrifuging the liquid obtained in the third step, wherein the centrifugation is carried out at the rotating speed of 1500-1800 rpm for 10-15 minutes, and then taking the supernatant for later use;
step five: freezing treatment: and D, adding dimethyl sulfoxide into the supernatant obtained in the fourth step, mixing, storing at low temperature overnight after mixing, and finally transferring into liquid nitrogen for long-term storage.
In the second step, 0.03mL/cm is added to the cells20.1% pancreatin and 0.02% EDTA, and a digestion time of 25min, in steps three according to 5000 cells/cm28000 cells/cm2The passage density of the umbilical cord mesenchymal stem cells is increased, and the quality of the cryopreservation protection solution for the umbilical cord mesenchymal stem cells is effectively guaranteed.
According to the invention, by the technical process, the use of bovine serum can be effectively avoided, so that heterologous viruses and sensitization sources are introduced as little as possible, and the quality of the cryopreservation protection solution for the umbilical cord mesenchymal stem cells can be effectively improved.
Example 2: the invention provides a technical scheme that:
a preparation process of a cryopreservation protection solution for umbilical cord mesenchymal stem cells comprises the following steps:
the method comprises the following steps: cleaning treatment: firstly, using sterilized surgical scissors to cut and spread umbilical cord tissues, fixing the spread umbilical cord tissues, then using a disinfectant to clean the surfaces of the umbilical cord tissues, using a cotton ball to dip the disinfectant to repeatedly disinfect and clean the surfaces of the umbilical cord during cleaning, wherein the disinfection and cleaning frequency is 3-5 times, then using a cell pretreatment cleaning buffer solution to clean the umbilical cord tissues, and during cleaning, using the cotton ball to dip the buffer solution to repeatedly clean the umbilical cord tissues, wherein the cleaning frequency is 3-5 times, so that the proportion of red blood cells on the umbilical cord tissues is effectively reduced, and then collecting the umbilical cord tissues for later use;
step two: and (3) digestion treatment: then, carrying out shearing treatment on the umbilical cord tissue obtained in the step one, and controlling the shearing size of the umbilical cord tissue during the shearing treatment so that the area of the upper end surface of a single umbilical cord tissue is controlled to be 0.08cm2-0.2cm2Adding pancreatin and EDTA into the minced umbilical cord tissue for digestion treatment, wherein during the digestion treatment, the pancreatin and EDTA completely immerse the umbilical cord tissue, during the digestion treatment, the umbilical cord tissue is repeatedly turned over, then the umbilical cord tissue is removed after the digestion treatment, then a mesenchymal stem cell culture medium is added into an enzymolysis liquid, so that the digestion is stopped, finally, the cells obtained after the enzymolysis are cleaned, and finally, a cell suspension is obtained;
step three: cell culture: centrifuging the cells subjected to enzymolysis and digestion obtained in the step two, wherein during centrifugation, the cells are centrifuged at a rotating speed of 5000-8000 rpm to ensure the rupture of the cells, and then performing density passage after complete culture medium reselection to continuously grow the cells for 24-72 h;
step four: centrifuging and taking a supernatant: centrifuging the liquid obtained in the third step, wherein the centrifugation is carried out at the rotating speed of 1500-1800 rpm for 10-15 minutes, and then taking the supernatant for later use;
step five: freezing treatment: and D, adding dimethyl sulfoxide into the supernatant obtained in the fourth step, mixing, storing at low temperature overnight after mixing, and finally transferring into liquid nitrogen for long-term storage.
In the second step, 0.02mL/cm is added to the cells20.2% of pancreatin and 0.03% of EDTA, and a digestion time of 20min, in steps three according to 5000 cells/cm28000 cells/cm2The passage density of the umbilical cord mesenchymal stem cells is increased, and the quality of the cryopreservation protection solution for the umbilical cord mesenchymal stem cells is effectively guaranteed.
According to the invention, by the technical process, the use of bovine serum can be effectively avoided, so that heterologous viruses and sensitization sources are introduced as little as possible, and the quality of the cryopreservation protection solution for the umbilical cord mesenchymal stem cells can be effectively improved.
Example 3: the invention provides a technical scheme that:
a preparation process of a cryopreservation protection solution for umbilical cord mesenchymal stem cells comprises the following steps:
the method comprises the following steps: cleaning treatment: firstly, using sterilized surgical scissors to cut and spread umbilical cord tissues, fixing the spread umbilical cord tissues, then using a disinfectant to clean the surfaces of the umbilical cord tissues, using a cotton ball to dip the disinfectant to repeatedly disinfect and clean the surfaces of the umbilical cord during cleaning, wherein the disinfection and cleaning frequency is 3-5 times, then using a cell pretreatment cleaning buffer solution to clean the umbilical cord tissues, and during cleaning, using the cotton ball to dip the buffer solution to repeatedly clean the umbilical cord tissues, wherein the cleaning frequency is 3-5 times, so that the proportion of red blood cells on the umbilical cord tissues is effectively reduced, and then collecting the umbilical cord tissues for later use;
step two: and (3) digestion treatment: then, carrying out shearing treatment on the umbilical cord tissue obtained in the step one, and controlling the shearing size of the umbilical cord tissue during the shearing treatment so that the area of the upper end surface of a single umbilical cord tissue is controlled to be 0.08cm2-0.2cm2Adding pancreatin and EDTA into the minced umbilical cord tissue for digestion treatment, wherein during the digestion treatment, the pancreatin and EDTA completely immerse the umbilical cord tissue, during the digestion treatment, the umbilical cord tissue is repeatedly turned over, then the umbilical cord tissue is removed after the digestion treatment, then a mesenchymal stem cell culture medium is added into an enzymolysis liquid, so that the digestion is stopped, finally, the cells obtained after the enzymolysis are cleaned, and finally, a cell suspension is obtained;
step three: cell culture: centrifuging the cells subjected to enzymolysis and digestion obtained in the step two, wherein during centrifugation, the cells are centrifuged at a rotating speed of 5000-8000 rpm to ensure the rupture of the cells, and then performing density passage after complete culture medium reselection to continuously grow the cells for 24-72 h;
step four: centrifuging and taking a supernatant: centrifuging the liquid obtained in the third step, wherein the centrifugation is carried out at the rotating speed of 1500-1800 rpm for 10-15 minutes, and then taking the supernatant for later use;
step five: freezing treatment: and D, adding dimethyl sulfoxide into the supernatant obtained in the fourth step, mixing, storing at low temperature overnight after mixing, and finally transferring into liquid nitrogen for long-term storage.
In the second step, 0.01mL/cm is added to the cells20.3% of pancreatin and 0.04% of EDTA, and the digestion time is 15min, in step three according to 5000 cells/cm28000 cells/cm2The passage density of the umbilical cord mesenchymal stem cells is increased, and the quality of the cryopreservation protection solution for the umbilical cord mesenchymal stem cells is effectively guaranteed.
According to the invention, by the technical process, the use of bovine serum can be effectively avoided, so that heterologous viruses and sensitization sources are introduced as little as possible, and the quality of the cryopreservation protection solution for the umbilical cord mesenchymal stem cells can be effectively improved.
The principles and embodiments of the present invention are explained herein using specific examples, which are presented only to assist in understanding the method and its core concepts of the present invention. The foregoing is only a preferred embodiment of the present invention, and it should be noted that there are objectively infinite specific structures due to the limited character expressions, and it will be apparent to those skilled in the art that a plurality of modifications, decorations or changes may be made without departing from the principle of the present invention, and the technical features described above may be combined in a suitable manner; such modifications, variations, combinations, or adaptations of the invention using its spirit and scope, as defined by the claims, may be directed to other uses and embodiments.

Claims (5)

the method comprises the following steps: cleaning treatment: firstly, using sterilized surgical scissors to cut and spread umbilical cord tissues, fixing the spread umbilical cord tissues, then using a disinfectant to clean the surfaces of the umbilical cord tissues, using a cotton ball to dip the disinfectant to repeatedly disinfect and clean the surfaces of the umbilical cord during cleaning, wherein the disinfection and cleaning frequency is 3-5 times, then using a cell pretreatment cleaning buffer solution to clean the umbilical cord tissues, and during cleaning, using the cotton ball to dip the buffer solution to repeatedly clean the umbilical cord tissues, wherein the cleaning frequency is 3-5 times, so that the proportion of red blood cells on the umbilical cord tissues is effectively reduced, and then collecting the umbilical cord tissues for later use;
step two: and (3) digestion treatment: then, carrying out shearing treatment on the umbilical cord tissue obtained in the step one, and controlling the shearing size of the umbilical cord tissue during the shearing treatment so that the area of the upper end surface of a single umbilical cord tissue is controlled to be 0.08cm2-0.2cm2Adding pancreatin and EDTA into the minced umbilical cord tissue for digestion treatment, wherein during the digestion treatment, the pancreatin and EDTA completely immerse the umbilical cord tissue, during the digestion treatment, the umbilical cord tissue is repeatedly turned over, then the umbilical cord tissue is removed after the digestion treatment, then a mesenchymal stem cell culture medium is added into an enzymolysis liquid, so that the digestion is stopped, finally, the cells obtained after the enzymolysis are cleaned, and finally, a cell suspension is obtained;
CN202011399412.9A2020-12-022020-12-02Preparation process of cryopreservation protection solution for umbilical cord mesenchymal stem cellsPendingCN112514888A (en)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication numberPriority datePublication dateAssigneeTitle
CN102660497A (en)*2012-05-212012-09-12博雅干细胞科技有限公司Method for freezing and reviving umbilical cord tissues and for separating and increasing stem cells
CN102660502A (en)*2012-05-212012-09-12博雅干细胞科技有限公司Methods for freezing and thawing whole cell of umbilical cord and separating and augmenting stem cell
CN105145547A (en)*2015-10-282015-12-16广州赛莱拉干细胞科技股份有限公司Cryopreservation protective fluid and method for umbilical cord mesenchymal stem cells
US20200165571A1 (en)*2015-12-112020-05-28Lei GuoMethod for separating and culturing mesenchymal stem cells from wharton's jelly tissue of umbilical cord

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication numberPriority datePublication dateAssigneeTitle
CN102660497A (en)*2012-05-212012-09-12博雅干细胞科技有限公司Method for freezing and reviving umbilical cord tissues and for separating and increasing stem cells
CN102660502A (en)*2012-05-212012-09-12博雅干细胞科技有限公司Methods for freezing and thawing whole cell of umbilical cord and separating and augmenting stem cell
CN105145547A (en)*2015-10-282015-12-16广州赛莱拉干细胞科技股份有限公司Cryopreservation protective fluid and method for umbilical cord mesenchymal stem cells
US20200165571A1 (en)*2015-12-112020-05-28Lei GuoMethod for separating and culturing mesenchymal stem cells from wharton's jelly tissue of umbilical cord

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Application publication date:20210319


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