CF-M801 was developed by inducing the differentiation of umbilical cord-derived mesenchymal stem cells into osteoblasts. It not only has the bone regenerative properties but also the characteristic of secreting the vascular inducing factors, thereby secreting the proteins directly involved in bone regeneration. It has the dual function: it acts as a replacement to regenerate the defective area andan induction of bone formation by increasing the secretion of angiogenesis-inducing factors and osteogenic differentiation proteins (Paracrine effect).Therefore, CF-M801 is the cell therapy agent with the excellent ability to promote the bone formation and regeneration by meeting the necessary elements for bone regeneration: Osteoinduction, Osteogenesis, and Angiogenesis.
Mode of Action
Osteogenesis + Angiogenesis → Improving the efficiency of bone regeneration
(Reduction of bone formation time)
Markers of osteogenic differentiation
We established the identification markers to distinguish the early osteoblasts from undifferentiated cells.CD73 and CD105(undifferentiated stem cell markers) are decreased, and expression of RUNX2 and COL1A1 gene (osteoblast markers) are high.RUNX2 is the master regulator of osteocyte differentiation that differentiates the mesenchymal stem cells into osteoblasts. Early-stage osteoblasts have Runx2+ and proliferative ability.In addition, mineralization progresses as it gradually differentiates into the mature osteoblast.
Osteoblast differentiation
Osteoblast of early stage
Osteoblast remains in the state without stopping the cell division for a certain period of time.After this period, the differentiation progresses, and they gradually lose their ability to divide and differentiate into the mature osteocytes along with the development of extracellular matrix (ECM).
<Model of the reciprocal relationship between proliferation and
differentiation in normal diploid cells during the rat osteoblast
developmental sequence>
<CF-M801 as the osteoblast of early stage>
CF-M801 is the osteoblast of early stage. We confirmed that in CF-M801, with the reduced cell proliferation ability, the cell cycle does not completely stop. Also, as differentiation progresses, the cell proliferation ability gradually decreases, and differentiation progresses along with ECM development.
<Ki-67 expression in UCMSC vs DP>
Function of angiogenesis induction
In order for bone to regenerate, the blood vessel formation must occur first.It was confirmed that UCMSC secreted the highest amount of VEGF among the mesenchymal stem cells, and as a result ofthe co-culture with vascular endothelial cells, it was also confirmed that the thickest blood vessels were formed.
<Confirmation of neovascularization induction by mesenchymal stem cells of various origins>
<Level of VEGF expression in naive UC-MSC, CF-M801>
We analyzed the degree of angiogenesis by inducingthe angiogenesis in CF-M801 (Angiogenesis assay).As a result, when the umbilical cord-derived undifferentiated raw cells and the cell therapy agents are co-cultured, the formation of blood vessels in vascular endothelial cells is induced as well as when the VEFG is artificially added.
<Effect of inducing angiogenesis by cell therapy agent>
