Search

KR-102958780-B1 - COMPOSITION FOR DIFFERENTIATION OF STEM CELLS

KR102958780B1KR 102958780 B1KR102958780 B1KR 102958780B1KR-102958780-B1

Abstract

The present invention relates to a composition for enhancing the osteogenic differentiation efficiency of adipose-derived stem cells. The present invention reveals that differentiation efficiency can be maximized by restoring damaged paracrine function through treatment with FGF2 and/or HGF during the early stages of differentiation of ADSCs derived from older donors with reduced differentiation efficiency. Therefore, it can be utilized as an in vitro processing technology for enhancing stem cell differentiation efficiency before or during adipose stem cell transplantation.

Inventors

  • 홍현숙
  • 황대연
  • 박정섭

Assignees

  • 경희대학교 산학협력단
  • (주) 엘피스셀테라퓨틱스

Dates

Publication Date
20260508
Application Date
20221026

Claims (18)

  1. A composition for promoting stem cell differentiation comprising FGF (fibroblast growth factor) 2 and HGF (hepatocyte growth factor) as active ingredients, The concentration of the above FGF2 is 0.5 to 10 ng/mL, and The concentration of the above HGF is 5 to 100 ng/mL, and A composition for promoting stem cell differentiation, wherein the above FGF2 and HGF are treated within 7 days after differentiation induction.
  2. delete
  3. delete
  4. delete
  5. A composition for promoting stem cell differentiation, wherein, in claim 1, the stem cells are adult stem cells.
  6. A composition for promoting stem cell differentiation according to claim 5, wherein the adult stem cells are derived from at least one of bone marrow, blood, brain, skin, fat, umbilical cord blood, and Wharton's jelly of the umbilical cord.
  7. A composition for promoting stem cell differentiation, which promotes the differentiation of stem cells into osteocytes in claim 1.
  8. A composition for promoting stem cell differentiation, wherein, in claim 1, it promotes the differentiation of adipose-derived stem cells (ADSCs) into osteoblasts.
  9. A composition for promoting stem cell differentiation according to claim 1, wherein the stem cells are adipose-derived stem cells derived from an elderly donor aged 50 to 80 years.
  10. A composition for inducing bone differentiation comprising FGF2 and HGF as active ingredients, The concentration of the above FGF2 is 0.5 to 10 ng/mL, and The concentration of the above HGF is 5 to 100 ng/mL, and A composition for inducing bone differentiation, wherein the above FGF2 and HGF are treated within 7 days after differentiation induction.
  11. A composition for inducing bone differentiation according to claim 10, which increases the differentiation-inducing effect when inducing osteocytic differentiation.
  12. A composition for inducing bone differentiation, wherein, in claim 11, the bone cells are osteoblasts.
  13. A pharmaceutical composition for the prevention or treatment of bone disease comprising FGF2 and HGF as active ingredients, The concentration of the above FGF2 is 0.5 to 10 ng/mL, and The concentration of the above HGF is 5 to 100 ng/mL, and The above FGF2 and HGF are administered within 7 days after differentiation induction, and A pharmaceutical composition for the prevention or treatment of a bone disease, wherein the bone disease is one or more selected from the group consisting of arthritis, bone defect disease, osteoporosis, osteopenia, osteolytic metastasis, senile kyphosis, and Paget's disease.
  14. delete
  15. In a stem cell transplant adjuvant comprising FGF2 and HGF, The concentration of the above FGF2 is 0.5 to 10 ng/mL, and The concentration of the above HGF is 5 to 100 ng/mL, and The above FGF2 and HGF are stem cell transplant adjuvants that are administered within 7 days after differentiation induction.
  16. (a) a step of isolating adipose-derived adult stem cells extracted from adipocytes isolated from an individual; and (b) A method for improving the osteogenic ability of stem cells, comprising the step of treating stem cells with FGF2 and HGF, wherein The concentration of the above FGF2 is 0.5 to 10 ng/mL, and The concentration of the above HGF is 5 to 100 ng/mL, and A method for improving the osteogenic ability of stem cells, wherein the above FGF2 and HGF are treated within 7 days after differentiation induction.
  17. A method for improving the osteogenic differentiation ability of stem cells, wherein step (b) is replacing with a differentiation medium containing FGF2 and HGF.
  18. A method for improving the osteogenic differentiation ability of stem cells, wherein, in paragraph 16, the differentiation ability of adipose-derived stem cells into osteoblasts is improved.

Description

Composition for the Promotion of Stem Cell Differentiation The present invention relates to a composition for promoting stem cell differentiation, and more specifically, to a composition for enhancing the osteogenic differentiation efficiency of adipose-derived stem cells. Cell therapy products are defined as pharmaceuticals used for therapeutic, diagnostic, and preventive purposes by employing a series of actions (more-than-minimal manipulation) such as proliferating or selecting living autologous, allogeneic, or xenogeneic cells in vitro, or altering their biological characteristics through other methods, in order to restore the function of cells and tissues. Among these, stem cell therapies specifically refer to cases where stem cells are used; currently, active development is underway in major application areas such as neurological diseases, heart diseases, lung diseases, liver diseases, and cancer, where the recovery and regeneration of lost cells are essential but do not occur naturally. Stem cells are cells capable of differentiating into various cells that constitute biological tissues; they collectively refer to undifferentiated cells in a pre-differentiation stage that can be obtained from the tissues of embryos, fetuses, and adults. Stem cells undergo differentiation into specific cells in response to differentiation stimuli (environment). Unlike cells that have completed differentiation and ceased cell division, stem cells possess the characteristic of proliferation (expansion) as they can self-renewal by producing identical cells through cell division. Furthermore, they are characterized by plasticity in differentiation, as they can differentiate into other cells under different environments or different differentiation stimuli. Stem cells are broadly classified into embryonic stem cells (ES cells), which are obtained from embryos and possess totipotent potential to differentiate into all cell types, and adult stem cells, which possess multipotency and are obtained from various tissues. The inner cell mass of the blastocyst, the early stage of embryonic development, is the part that will eventually form the fetus. Embryonic stem cells formed from this inner cell mass are theoretically stem cells with the potential to differentiate into all tissue cells that constitute an individual. In other words, embryonic stem cells are undifferentiated cells capable of unlimited proliferation and can differentiate into any cell type, whereas adult stem cells are cells with the ability to differentiate into various cell types. Adult stem cells can be obtained from various parts, such as bone marrow, dental tissue, and peripheral blood; in particular, adipose tissue is known as an abundant source of stem cells with diverse potential. Like other adult stem cells, ADSCs (adipose-derived stem cells) are derived from mesenchymal tissue and can differentiate not only into various types of cells such as adipocytes, fibroblasts, smooth muscle cells, endothelial cells, and preadipocytes, but also into epithelial, cartilage, nerve, fat, and muscle cells. In addition, it has been reported that the cell proliferation rate is rapid, the adipose tissue serving as the material can be extracted in large quantities incidentally during the liposuction process, making it easy to obtain, and that it is not only easily separated by enzymes but also has a low incidence of disease after transplantation. Meanwhile, bone is maintained through the balance between bone formation by osteoblasts and osteoclasts (Alliston T. et al. Interfering with bone remodelling. Nature. 2002;416:686-687.). Maintaining the balance between osteoblasts and osteoclasts is an essential element for maintaining bone homeostasis. The disruption of this balance due to aging occurs when the bone-destroying capacity of osteoclasts exceeds the bone-forming capacity of osteoblasts, thereby breaking down homeostasis. This implies that inhibiting bone resorption by osteoclasts is crucial for the prevention and treatment of age-related bone diseases (Tanaka, Y., et al., 2005). Excessive osteoclast activity exceeding osteoblast activity causes various bone diseases and is characterized by a decrease in bone mass and structural deterioration of the skeleton (Kim N. et al. Osteoclast differentiation independent of the TRANCE-RANK-TRAF6 axis. J Exp Med. 2005;202:589-595.). Intractable bone diseases among these include osteoporosis, non-union fractures, osteonecrosis, osteomalacia, and bone defects. Osteoporosis, also known as osteoporosis or osteoporosis, refers to a metabolic bone disease characterized by a quantitative decrease in bone components as the primary lesion, characterized by a significantly reduced bone mass compared to normal individuals. Generally, the pathology of osteoporosis itself is often asymptomatic or presents with mild symptoms; however, once a fracture occurs, treatment is typically difficult, and even with bone fixation surgery, full recovery i