Unlock instant, AI-driven research and patent intelligence for your innovation.

Composition for proliferation, differentiation promotion, or senescence inhibition of stem cells, containing JAK1 inhibitor as active ingredient

A technology of active ingredients and cell proliferation, applied to medical preparations containing active ingredients, organic active ingredients, animal cells, etc., can solve the problems of inhibiting aging restrictions, stem cell survival rate, and rising costs

Inactive Publication Date: 2018-12-21
UNIV OF ULSAN FOUND FOR IND COOPERATION
View PDF1 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] However, since Bmi-1 itself is an oncogene that may cause tumors (Haupt, Y. et al., Oncogene, 8; 3161-3164, 1993; Bruggeman, S.W. et al. Cancer cell 12; 328-341 2007 ), therefore, the possibility of tumor formation cannot be ruled out when mesenchymal stem cells treated with Bmi-1 and hTERT (telemorase catalytic subunit) are used as cell therapy agents
In addition, the method of treating FGF-2 in culture requires continuous use of relatively high-priced FGF-2 during culture, which increases the cost, and only temporary cell growth is expected compared to the inhibition of aging by FGF-2 Increased effect, so there is a limitation in inhibiting aging
[0005] In addition, various biological stem cell therapeutic agents have been tried in the past to treat diseases, but due to the aging of inflammatory stem cells, there is a problem with the survival rate of stem cells after transplantation, so there is a limitation that it is difficult to ensure the therapeutic effect of stem cells

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Composition for proliferation, differentiation promotion, or senescence inhibition of stem cells, containing JAK1 inhibitor as active ingredient
  • Composition for proliferation, differentiation promotion, or senescence inhibition of stem cells, containing JAK1 inhibitor as active ingredient
  • Composition for proliferation, differentiation promotion, or senescence inhibition of stem cells, containing JAK1 inhibitor as active ingredient

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0085] Confirmation of resistance to inflammatory aging following treatment with tofacitinib as a JAK1 inhibitor

[0086] Confirmation that aging of stem cells was reduced with tofacitinib treatment

[0087] In order to confirm whether there is an effect of reducing aging of stem cells by tofacitinib treatment, the present inventors confirmed using SA-b-gal staining, which is a representative technique for measuring cell aging.

[0088] More specifically, stem cells were plated in 6-well plates (2×10 4 cell / well) and treated with poly IC (1ug / ml) 1 day later. Tofacitinib (1ug / ml) was pretreated 2 hours before poly IC treatment. After 2 days of poly IC treatment, the degree of aging was measured using a senescence cell shistochemical staining kit (CS0030, Sigma). For this purpose, after washing twice with phosphate buffered saline (PBS), fixation buffer (fixation buffer; 2% formaldehyde, 0.2% glutaraldehyde, 7.04mM Na 2 HPO 4 , 1.47mM KH 2 PO 4 , 0.137M NaCl, and 2.6...

Embodiment 2

[0118] Inflammatory aging resistance confirmed in JAK1 knockout stem cells

[0119] Confirmation of reduction in aging of stem cells following JAK1 knockdown

[0120] The present inventors cloned the JAK1 gide RNA sequence in the plentiCRISPRv2 vector in order to create JAK1 knockout cells. Thereafter, for packaging as lentivirus, the plentiCRISPR-JAK1, pMD2.G and psPAX2 plasmids were transfected into 293T cells. After 3 days of transfection, stem cells were treated with virus-containing medium to infect plentiCRISPR-JAK1 lentivirus. Puromycin selection was performed for 2 days using the puromycin resistance gene present in the plentiCRISPRv2 vector, and then only surviving cells were cultured. Knockout of the JAK1 gene was confirmed by Western blot, sequencing (Western blot - see Figure 3C).

[0121] In order to confirm whether the JAK1-knockout cells produced as described above have an effect of reducing stem cell aging, it was confirmed by SA-b-gal staining, which i...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The present invention relates to a composition for proliferation, differentiation promotion, and senescence inhibition of stem cells, containing a JAK1 inhibitor as an active ingredient. JAK1 inhibitor-treated stem cells or JAK1 knockout stem cells, of the present invention, have an activity for decreasing senescence and increasing the survival rate of the stem cells, thereby being usable in a composition for proliferation, differentiation promotion, and senescence inhibition of stem cells. In addition, JAK1 knockout stem cells have an activity for inhibiting or decreasing the expression of HLA-A or HLA-B, which is an immunogenicity related protein, and promoting or increasing the expression of TGF-b or HGF, which is a T cell activity inhibitory protein, thereby also being usable in the prevention or treatment of immune diseases.

Description

technical field [0001] The present invention relates to a composition for proliferation, differentiation promotion and aging suppression of stem cells containing a JAK1 inhibitor as an active ingredient. Background technique [0002] Stem cells (stem cells) are stem cells with multi-differentiation properties produced by various living cells such as bone marrow, umbilical cord blood, placenta (or placental tissue cells), fat (or adipose tissue cells). For example, mesenchymal stem cells produced from bone marrow (bone marrow) are being researched in various ways for the development of cell therapy agents due to their multi-differentiation ability to differentiate into adipose tissue, bone / cartilage tissue, and muscle tissue. In addition, similar to other human primary cultured cells, mesenchymal stem cells are known to sharply reduce cell division when cultured in vitro due to a senescence mechanism unrelated to telomere shortening (Shibata , K.R. et al. Stem cells, 25; 237...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C12N5/0775A61K35/28A61P37/00
CPCA61K31/519A61K31/541A61P37/02A61K35/28C12N5/0662C12N2501/727C12N2501/40
Inventor 金昇厚金相润李香珠
Owner UNIV OF ULSAN FOUND FOR IND COOPERATION