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Application of mesenchymal stem cells combined with TPO and analogues thereof in treatment of chronic myeloid leukemia

A myeloid leukemia and mesenchymal stem cell technology, applied in animal cells, vertebrate cells, bone/connective tissue cells, etc., to induce differentiation of leukemia cells and avoid drug resistance

Pending Publication Date: 2021-12-07
NANJING UNIV
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  • Abstract
  • Description
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  • Application Information

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Problems solved by technology

MPL is continuously expressed in normal hematopoietic stem cells and megakaryocytes, and studies have found that the expression of this receptor gradually decreases with the progression of CML, which may become a breakthrough in the future treatment of CML

Method used

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  • Application of mesenchymal stem cells combined with TPO and analogues thereof in treatment of chronic myeloid leukemia
  • Application of mesenchymal stem cells combined with TPO and analogues thereof in treatment of chronic myeloid leukemia
  • Application of mesenchymal stem cells combined with TPO and analogues thereof in treatment of chronic myeloid leukemia

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Embodiment Construction

[0021] The principles and features of the present invention are described below in conjunction with examples, which are only used to explain the present invention and are not used to limit the scope of the present invention.

[0022] Isolation and subculture of umbilical cord mesenchymal stem cells

[0023] 1. Prepare tissue digestion enzymes (type II collagenase 250U / ml, dispase 100U / ml, hyaluronidase 10U / ml), dissolve in α-MEM medium at 37°C, filter and sterilize with a 0.22μm filter for later use ;

[0024] 2. Take the umbilical cord tissue of the newborn baby, put the umbilical cord into a petri dish, wash it with PBS containing 0.1% penicillin-streptomycin double antibody, put it into α-MEM medium, peel off the three blood vessels, and cut the umbilical cord into pieces 1-2mm 3 organization block;

[0025] 3. Mix the shredded tissue pieces and the prepared tissue digestion enzyme solution in a volume ratio of 1:1 in a 50ml centrifuge tube, digest at 37°C, 200rpm for 3 ...

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Abstract

The invention belongs to the technical field of medical biology, and particularly relates to application of umbilical cord-derived mesenchymal stem cells combined with TPO and analogues thereof in preparation of drugs for treating chronic myelogenous leukemia. The mesenchymal stem cells are human-derived umbilical cord mesenchymal stem cells (UC-MSCs), can efficiently induce differentiation of chronic myeloid leukemia cells after being combined with a TPO analogue Eltrombopag, and the capability is realized by secreting TPO by MSCs and inducing leukemia cells to express a TPO receptor (MPL); and compared with chemotherapy, mesenchymal stem cell transplantation is lower in toxic and side effects, has low immunogenicity and meets clinical requirements, and the Eltrombopag is a clinically approved drug. The method provides a new thought for stem cell transplantation treatment of myeloid leukemia, and can be applied to differentiation treatment of myeloid leukemia.

Description

technical field [0001] The invention belongs to the technical field of medicine and biology, and in particular relates to a combination method of mesenchymal stem cells, TPO and its analogs and its application in the treatment of chronic myelogenous leukemia. Background technique [0002] Chronic myeloid leukemia (CML) is an uncontrolled proliferation of stem / progenitor cells in hematopoietic stem cells (HSC) due to chromosomal translocation t(9;22)(q34;q11) and arrested differentiation resulting in proliferative neoplasms in which clonal expansion of leukemic cells is driven by a BCR-ABL fusion protein with constitutive tyrosine kinase activity. Tyrosine kinase inhibitors (TKIs), such as imatinib mesylate (IM), can target the pathogenic protein BCR-ABL, and are currently the standard treatment for CML. However, CML patients with IM drug resistance progress rapidly and have a poor prognosis. Therefore, IM drug resistance has become an urgent problem to be solved in CML trea...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/19A61K35/28A61P35/02C12N5/0775A61K31/4152
CPCA61K38/196A61K35/28A61K31/4152A61P35/02C12N5/0668C12N5/0662A61K2300/00
Inventor 沈萍萍左诗曼孙璐琛杨南飞郑薇
Owner NANJING UNIV
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