CN115039759B - Erythrocyte preservation solution and application thereof - Google Patents

Erythrocyte preservation solution and application thereof Download PDF

Info

Publication number
CN115039759B
CN115039759B CN202210215718.7A CN202210215718A CN115039759B CN 115039759 B CN115039759 B CN 115039759B CN 202210215718 A CN202210215718 A CN 202210215718A CN 115039759 B CN115039759 B CN 115039759B
Authority
CN
China
Prior art keywords
red blood
blood cell
cell preservation
preservation solution
solution
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN202210215718.7A
Other languages
Chinese (zh)
Other versions
CN115039759A (en
Inventor
张磊
王文天
张文慧
杨仁池
池颖
李慧媛
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Cell Ecology Haihe Laboratory
Institute of Hematology and Blood Diseases Hospital of CAMS and PUMC
Original Assignee
Cell Ecology Haihe Laboratory
Institute of Hematology and Blood Diseases Hospital of CAMS and PUMC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Cell Ecology Haihe Laboratory, Institute of Hematology and Blood Diseases Hospital of CAMS and PUMC filed Critical Cell Ecology Haihe Laboratory
Priority to CN202210215718.7A priority Critical patent/CN115039759B/en
Publication of CN115039759A publication Critical patent/CN115039759A/en
Priority to PCT/CN2023/078627 priority patent/WO2023169249A1/en
Application granted granted Critical
Publication of CN115039759B publication Critical patent/CN115039759B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N1/00—Preservation of bodies of humans or animals, or parts thereof
    • A01N1/02—Preservation of living parts
    • A01N1/0205—Chemical aspects
    • A01N1/021—Preservation or perfusion media, liquids, solids or gases used in the preservation of cells, tissue, organs or bodily fluids
    • A01N1/0226—Physiologically active agents, i.e. substances affecting physiological processes of cells and tissue to be preserved, e.g. anti-oxidants or nutrients
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N1/00—Preservation of bodies of humans or animals, or parts thereof
    • A01N1/02—Preservation of living parts
    • A01N1/0205—Chemical aspects
    • A01N1/021—Preservation or perfusion media, liquids, solids or gases used in the preservation of cells, tissue, organs or bodily fluids
    • A01N1/0221—Freeze-process protecting agents, i.e. substances protecting cells from effects of the physical process, e.g. cryoprotectants, osmolarity regulators like oncotic agents
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention provides a red blood cell preservation solution and application thereof. The red blood cell preservation solution comprises a red blood cell preservation base solution and an antioxidant, wherein the antioxidant comprises uric acid. The red blood cell preservation solution can be used for preserving red blood cells in vitro for a long time, and can further activate the red blood cells by introducing uric acid into a red blood cell preservation base solution as an antioxidant, so that the anti-hemolytic apoptosis capability of the red blood cells is remarkably enhanced, and the in vitro preservation time is remarkably prolonged, so that the red blood cell preservation solution has great application value for the ultra-long-period in vitro low-temperature preservation of red blood cells for blood transfusion.

Description

Erythrocyte preservation solution and application thereof
Technical Field
The invention belongs to the technical field of medical treatment, and particularly relates to a red blood cell preservation solution and application thereof.
Background
Red Blood Cells (RBC) are the major constituent cells of human blood, RBC content in adult bloodUp to 5X 10 12 /L(5×10 9 Per mL,5000 million/mL) and hematocrit (the percentage of red blood cells in whole blood) of 40-50%. The primary physiological function of erythrocytes is to transport oxygen from the lungs and release it to the body for metabolism. In emergency cases such as blood loss, anemia and the like, the number of red blood cells of the organism is seriously reduced, and life safety is endangered. Therefore, erythrocyte transfusion has become a fundamental treatment for clinically critical patients. Currently, red blood cells for transfusion emergency are mainly from social donation, and then are separated by red blood cells and stored in red blood cell preservation solution. However, when blood is stored in a liquid matrix, a series of biochemical and structural changes to the red blood cells occur, i.e., damage to the red blood cells during storage can affect the survival of the red blood cells after transfusion and cause functional changes. At present, development of erythrocyte preservation solution has become an important point and a hot spot of research by a plurality of scholars.
CN1857312a discloses a erythrocyte cryoprotectant comprising small molecule sugar (trehalose, glucose, sucrose, maltose, fructose or mannitol), sodium chloride, potassium dihydrogen phosphate and disodium hydrogen phosphate. The protective liquid can realize deep low-temperature preservation of the red blood cells, reduce the hemolysis rate of the red blood cells, greatly simplify the washing procedure of the red blood cells after thawing, but the preservation time of the protective liquid on the red blood cells needs to be further improved.
CN111919835a discloses a preservation solution for maintaining erythrocyte activity, comprising: heparin-poloxamer, glycine, monopotassium phosphate, basic fibroblast growth factor and trimethoprim can ensure the oxygen carrying activity of erythrocytes, but the preservation solution only maintains the activity of erythrocytes by increasing the effective concentration of nitric oxide gas, and no study on apoptosis and hemolysis of erythrocytes is disclosed.
CN104705287a discloses a red blood cell cryopreservation solution comprising: tripotassium citrate monohydrate, sodium dihydrogen phosphate dihydrate, disodium hydrogen phosphate dodecahydrate and glycerin. The preservation solution can realize physiological balance inside and outside erythrocyte membranes and avoid rupture of the erythrocyte membranes, but the existence of glycerol can cause complicated washing process in later use of the erythrocyte, thereby causing burden to medical staff.
Based on the above research, it can be seen that the development of the red blood cell preservation solution at present is very much, and although the red blood cell preservation solution can obviously prolong the service life of red blood cells, the key anti-apoptosis and anti-hemolysis core technology of the red blood cells is not mastered, and the research on further improving the anti-apoptosis, anti-hemolysis and anti-natural disintegration capabilities of the red blood cell preservation solution on the red blood cells and prolonging the preservation time of the red blood cells is still needed.
Disclosure of Invention
Aiming at the defects and actual requirements of the prior art, the invention aims to provide a red blood cell preservation solution and application thereof. The red blood cell preservation solution can strongly protect red blood cells and extremely remarkably prolong the service life of the red blood cells.
In order to achieve the aim of the invention, the invention adopts the following technical scheme:
in a first aspect, the present invention provides a red blood cell preservation solution comprising a red blood cell preservation base solution and an antioxidant comprising uric acid.
According to the invention, uric acid is introduced into the erythrocyte preservation base solution as an antioxidant, so that erythrocytes can be further activated, the anti-hemolytic apoptosis capability of the erythrocytes is remarkably enhanced, the in-vitro preservation time is remarkably prolonged, and the method has great application value for the ultra-long-term in-vitro low-temperature preservation of erythrocytes for blood transfusion.
While hepatic xanthine dehydrogenase (xanthine dehydrogenase, XDH) is the rate-limiting enzyme for uric acid production, the lack of XDH enzyme in erythrocytes means that even if adenine (a precursor for uric acid production) is added to the existing erythrocyte preservation solution, erythrocytes cannot efficiently produce uric acid. Thus, unless added extracellularly, erythrocytes themselves are unable to store sufficient levels of uric acid. Uric acid is a purine metabolite specific to primates (humans, etc.). In other mammals, uric acid is further metabolized to allantoin for excretion with urine. Studies have demonstrated that uric acid, which is an antioxidant, can effectively increase the life span of model organisms, and thus uric acid is not only a metabolic end product in the human body, but also has important physiological functions.
In the present invention, the base red blood cell preservation solution may be a commercially available red blood cell preservation solution (including MAP preparation or Aldrich solution).
Wherein the MAP preparation contains trisodium citrate, citric acid, glucose, sodium dihydrogen phosphate, adenine, sodium chloride and mannitol.
The Alzhi liquid contains sodium chloride, sodium citrate, citric acid and glucose.
In the invention, the concentration of uric acid in the red blood cell preservation solution is 10-1000 mu M.
The 10-1000. Mu.M may be 10. Mu.M, 50. Mu.M, 100. Mu.M, 200. Mu.M, 300. Mu.M, 400. Mu.M, 500. Mu.M, 600. Mu.M, 700. Mu.M, 800. Mu.M, 900. Mu.M, 1000. Mu.M, etc.
Other values within the above numerical ranges are selectable, and will not be described in detail herein.
Preferably, the uric acid is present in the red blood cell preservation solution at a concentration of 200-800. Mu.M.
Further preferably, the uric acid is present in the red blood cell preservation solution at a concentration of 300 to 500. Mu.M.
The concentration of uric acid in the red blood cell preservation solution is 10-1000 mu M, which can ensure the protection of red blood cells, preferably 200-800 mu M, more preferably 300-500 mu M, because the normal value of uric acid level in human body is 100-300 mu M, and hyperuricemia can reach 500 mu M. In addition, according to the in vitro erythrocyte culture experiment of the invention, 300-500 mu M uric acid can extremely obviously protect erythrocytes and resist the hemolysis phenomenon induced by vitamin C. In addition, even without vitamin C, erythrocytes will naturally hemolyze in MAP nutrient solution, and the addition of uric acid can obviously protect erythrocytes against natural hemolysis reaction.
In the invention, the use temperature of the erythrocyte preservation solution is 4-10 ℃.
The temperature of 4-10deg.C can be 4deg.C, 4.5 deg.C, 5.5 deg.C, 6 deg.C, 6.5 deg.C, 7 deg.C, 7.5 deg.C, 8 deg.C, 8.5 deg.C, 9 deg.C, 9.5 deg.C or 10deg.C, etc.
Other values within the above numerical ranges are selectable, and will not be described in detail herein.
In a second aspect, the present invention provides a use of the red blood cell preservation solution according to the first aspect for preserving red blood cells in vitro.
Compared with the prior art, the invention has the following beneficial effects:
according to the invention, uric acid is introduced into the erythrocyte preservation base solution as an antioxidant, so that erythrocytes can be activated, the anti-hemolytic apoptosis capability of the erythrocytes is remarkably enhanced, and the membrane steady state of the erythrocytes is improved, thereby realizing long-term preservation of the erythrocytes in an optimal state, and having great application value for the ultra-long-term in-vitro low-temperature preservation of erythrocytes for blood transfusion.
Drawings
FIG. 1 is a graph showing the results of preservation of erythrocytes by the erythrocyte preservation solution obtained in example 1;
FIG. 2 is a graph showing the preservation result of erythrocytes by the erythrocyte preservation solution obtained in example 2;
FIG. 3 is a graph showing the preservation result of erythrocytes by the erythrocyte preservation solution obtained in example 3;
FIG. 4 is a graph showing the preservation result of red blood cells by the red blood cell preservation solution obtained in example 4;
FIG. 5 is a graph showing the preservation result of erythrocytes by the erythrocyte preservation solution obtained in example 5;
FIG. 6 is a graph showing the preservation result of erythrocytes by the erythrocyte preservation solution obtained in example 6;
FIG. 7 is a graph showing the preservation result of red blood cells by the red blood cell preservation solution obtained in comparative example 1;
FIG. 8 is a graph of apoptosis of erythrocytes in various dosing groups.
Detailed Description
The technical scheme of the invention is further described by the following specific embodiments. It will be apparent to those skilled in the art that the examples are merely to aid in understanding the invention and are not to be construed as a specific limitation thereof.
The corresponding materials and sources of raw materials in the following preparation examples, comparative examples and test examples were purchased as follows:
wherein, MAP reagent is purchased from Shanghai remote mu organism, and the model is R18099; the Aldrich fluid is purchased from Beijing Soy Bao, model R1016; uric acid was purchased from Shanghai source leaf organism under model S30610. The remaining materials and starting materials are available from other commercial sources without specific description.
Example 1
The present embodiment provides a red blood cell preservation solution, comprising: 1mL MAP reagent, 500. Mu.M uric acid.
Wherein 500. Mu.M refers to the concentration of uric acid in the red blood cell preservation solution.
Example 2
The present embodiment provides a red blood cell preservation solution, comprising: 1mL MAP reagent, 200. Mu.M uric acid.
Wherein 200. Mu.M refers to the concentration of uric acid in the red blood cell preservation solution.
Example 3
This example provides a red blood cell preservation solution differing from example 1 only in that the uric acid concentration in the red blood cell preservation solution is 10. Mu.M, and the remaining parameters remain the same as in example 1.
Example 4
This example provides a red blood cell preservation solution differing from example 1 only in that the uric acid concentration in the red blood cell preservation solution is 50. Mu.M, and the remaining parameters remain the same as in example 1.
Example 5
This example provides a red blood cell preservation solution differing from example 1 only in that the uric acid concentration in the red blood cell preservation solution is 100. Mu.M, and the remaining parameters remain the same as in example 1.
Example 6
This example provides a red blood cell preservation solution differing from example 1 only in that the uric acid concentration in the red blood cell preservation solution is 1000. Mu.M, and the remaining parameters remain the same as in example 1.
Comparative example 1
This comparative example provides a red blood cell preservation solution differing from example 1 only in that the red blood cell preservation solution does not include uric acid, and the remaining parameters remain the same as example 1.
Test example 1
This test example uses the red blood cell preservation solutions obtained in examples 1 to 6 and comparative example 1 to preserve red blood cells and observe the anti-hemolytic apoptosis ability of red blood cells.
The test method is as follows: the red blood cells were counted by taking 1mL of human peripheral blood. The cells were seeded in 12-well plates according to the standard of 50 ten thousand RBC/1mL red blood cell stock solution. Incubation at 37 ℃. After 24h observation was carried out under a microscope.
As shown in FIGS. 1-7, it can be seen from FIGS. 1-6 that the red blood cell preservation solution provided by the present invention still has a large number of RBCs in the non-hemolyzed finished state and bright cells after 24 hours of preservation time for red blood cells. Whereas the erythrocytes in FIG. 7 (which also contained no uric acid in their preservation) were substantially completely hemolyzed after 24h incubation at 37℃with only erythrocyte membrane structure remaining. By comparison, the specific protective effect of uric acid on erythrocytes can be fully demonstrated.
Test example 2
In this test example, 100 ten thousand erythrocytes were placed in 1640 medium, each in normoxic (21% O) 2 ) And low oxygen (5% O) 2 ) A1 mM Vitamin C (VC), 500. Mu.M Uric Acid (UA), 1mM VC+500. Mu.M UA double-factor dosing experiment was performed under the control, and after 3 days, observation was performed under a microscope.
As shown in FIG. 8, after 3 days of drug addition, compared with the control group (i.e., ctrl group), the 1mM VC group had a large number of hemolytic apoptosis, while the 500. Mu.M UA group had significantly reduced hemolytic apoptosis. In particular at 5% O 2 Nearly 100% of the erythrocytes are hemolyzed by VC, while at least 50% of erythrocytes have a complete cell membrane structure under UA protection. As can be seen from the vc+ua group, UA can strongly protect erythrocytes against VC-induced apoptosis by hemolysis.
In conclusion, uric acid is introduced into the erythrocyte preservation base solution as an antioxidant, so that erythrocytes can be activated, the anti-hemolytic apoptosis capacity of the erythrocytes is remarkably enhanced, and the membrane steady state of the erythrocytes is further improved, so that the erythrocytes in the optimal state can be preserved for a long time, and the method has great application value for the ultra-long-period in-vitro low-temperature preservation of erythrocytes for blood transfusion and has wide application prospect.
The applicant declares that the above is only a specific embodiment of the present invention, but the scope of the present invention is not limited thereto, and it should be apparent to those skilled in the art that any changes or substitutions that are easily conceivable within the technical scope of the present invention disclosed by the present invention fall within the scope of the present invention and the disclosure.

Claims (4)

1. The application of the red blood cell preservation solution in the in-vitro preservation of red blood cells and the anti-hemolysis apoptosis is characterized in that the red blood cell preservation solution consists of a red blood cell preservation base solution and an antioxidant;
the antioxidant is uric acid;
the uric acid concentration in the red blood cell preservation solution is 200-800 mu M.
2. The use according to claim 1, wherein the red blood cell preservation base fluid comprises: MAP formulation or Arshi solution.
3. The use according to claim 1, wherein the uric acid is present in the red blood cell preservation solution at a concentration of 300-500 μm.
4. The use according to claim 1, wherein the red blood cell preservation solution is used at a temperature of 4-10 ℃.
CN202210215718.7A 2022-03-07 2022-03-07 Erythrocyte preservation solution and application thereof Active CN115039759B (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
CN202210215718.7A CN115039759B (en) 2022-03-07 2022-03-07 Erythrocyte preservation solution and application thereof
PCT/CN2023/078627 WO2023169249A1 (en) 2022-03-07 2023-02-28 Red blood cell preservation solution and use thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202210215718.7A CN115039759B (en) 2022-03-07 2022-03-07 Erythrocyte preservation solution and application thereof

Publications (2)

Publication Number Publication Date
CN115039759A CN115039759A (en) 2022-09-13
CN115039759B true CN115039759B (en) 2023-11-03

Family

ID=83157282

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202210215718.7A Active CN115039759B (en) 2022-03-07 2022-03-07 Erythrocyte preservation solution and application thereof

Country Status (2)

Country Link
CN (1) CN115039759B (en)
WO (1) WO2023169249A1 (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115039759B (en) * 2022-03-07 2023-11-03 细胞生态海河实验室 Erythrocyte preservation solution and application thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1987004072A1 (en) * 1986-01-08 1987-07-16 Shobhana Vora Method and additives for improving the quality and shelf life of stored blood
CN113383769A (en) * 2021-06-29 2021-09-14 广州朗坤生物科技有限公司 Cell preservation solution and preparation method and application thereof
CN113557295A (en) * 2019-03-15 2021-10-26 株式会社美加细胞 Preservation solution for mammalian cells

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6020120A (en) * 1997-10-22 2000-02-01 South Alabama Medical Science Foundation Use of N-acetylcysteine to store red blood cells and a method of aging red cells with nitrogen
CN115039759B (en) * 2022-03-07 2023-11-03 细胞生态海河实验室 Erythrocyte preservation solution and application thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1987004072A1 (en) * 1986-01-08 1987-07-16 Shobhana Vora Method and additives for improving the quality and shelf life of stored blood
CN113557295A (en) * 2019-03-15 2021-10-26 株式会社美加细胞 Preservation solution for mammalian cells
CN113383769A (en) * 2021-06-29 2021-09-14 广州朗坤生物科技有限公司 Cell preservation solution and preparation method and application thereof

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
Restoration of Physiological Levels of Uric Acid and Ascorbic Acid Reroutes the Metabolism of Stored Red Blood Cells;Manon Bardyn;《Metabolites》;参见摘要和4.1. Preparation of Red Blood Cell Concentrates and Treatment *
Uric Acid Provides Protective Role in Red Blood Cells by Antioxidant Defense: A Hypothetical Analysis;Yunxiao Song;《Hindawi》;参见摘要 *
Uric acid variation among regular blood donors is indicative of red blood cell susceptibility to storage lesion markers: a new hypothesis tested;Vassilis L. Tzounakas;《TRANSFUSION》;参见摘要 *

Also Published As

Publication number Publication date
CN115039759A (en) 2022-09-13
WO2023169249A1 (en) 2023-09-14

Similar Documents

Publication Publication Date Title
Kager et al. Allopurinol in the treatment of visceral leishmaniasis
FISHER et al. A randomized study of phosphate therapy in the treatment of diabetic ketoacidosis
CN102349500B (en) Mesenchymal stem cell self-preserving liquid
CN107926933B (en) Cell preservation solution
US20050276794A1 (en) Composition and method for improving pancreatic islet cell survival
IE60063B1 (en) Synthetic, plasma-free, transfusible platelet storage medium
CN115039759B (en) Erythrocyte preservation solution and application thereof
US20030124503A1 (en) Pyruvate cardioplegia solutions for administration to the heart during cardiopulmonary surgery and methods of use thereof
Searcy et al. Congenital hemolytic anemia in the Basenji dog due to erythrocyte pyruvate kinase deficiency
CN112841174A (en) Cryopreservation liquid for long-term storage of human umbilical cord mesenchymal stem cells
CN109769797A (en) A kind of organ preservative fluid
Zabucchi et al. Exocytosis in human polymorphonuclear leukocytes induced by A 23187 and calcium
CN111513059B (en) Erythrocyte preservation solution and application thereof
CN111602648B (en) Immune cell serum-free cryopreservation liquid and cryopreservation method
Morshed et al. Propylene glycol-mediated cell injury in a primary culture of human proximal tubule cells
Silva et al. Oxygen cost of chloride transport in perfused rectal gland of Squalus acanthias
Granholm et al. The effect of combined respiratory and nonrespiratory alkalosis on energy metabolites and acid‐base parameters in the rat brain
CN102327289B (en) Erythrocyte freeze-dried powder preparation for injection and preparation method thereof
CN104107436B (en) A kind of preservation liquid for preserving dog whole blood and application thereof
CN104056270A (en) Histone deacetylase inhibitor for preparing medicaments for treating multi-organ damage
Utsunomiya et al. Myocardial protection with prostacyclin after lethal endotoxemia
CN101926823A (en) Penetrating agent used for peritoneal dialysate and dialysate thereof
CN115349515A (en) Cell preservation solution and cell preservation method
CN109349270A (en) Cell-preservation liquid and the method for saving cell using cell-preservation liquid
Luh et al. The effects of hyperosmolarity on the viability and function of endothelial cells

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
TA01 Transfer of patent application right

Effective date of registration: 20230106

Address after: 300462 2-1-101, Building 1-3, Bolong Industrial Park, north of Yuexin Road and east of Huixin Road, Binhai Science and Technology Park, Binhai New Area, Tianjin

Applicant after: Cell Ecology Haihe Laboratory

Applicant after: Hematology Hospital of Chinese Academy of Medical Sciences (Institute of Hematology, Chinese Academy of Medical Sciences)

Address before: 300020 No. 288, Nanjing Road, Heping District, Tianjin

Applicant before: Hematology Hospital of Chinese Academy of Medical Sciences (Institute of Hematology, Chinese Academy of Medical Sciences)

TA01 Transfer of patent application right
GR01 Patent grant
GR01 Patent grant