Differentiation of cells with a single molecule
Adenosine "persuaded" stem cells to save damaged bones
Daria Zagorskaya, Vesti
We have repeatedly written about the research of pluripotent stem cells, which are used to rejuvenate the body, treat diabetes, combat baldness and grow a variety of organs.
But, despite a large number of versatile studies, it is still very difficult to make stem cells turn into a strictly defined type of cells. Their differentiation (in fact, obtaining a "profession"), like a complex recipe, involves many ingredients and actions, which often makes the process expensive and inefficient.
Another problem that complicates the development of such therapy is that only stem cells obtained from tissues that do not form a teratoma tumor are suitable for transplantation.
Shyni Varghese from the University of California, San Diego and her colleagues have shown that pluripotent stem cells can be transformed into young bone cells - osteoblasts – by simply adding adenosine molecules to the medium. Like living osteoblasts from the human body, the resulting cells formed bone tissue permeated with blood vessels. After transplantation of artificially grown osteoblasts to mice with bone defects, the cells successfully took root and restored the damaged tissue without forming tumors.
A: scheme of an experiment to study the ability of bone tissue formation by osteoblasts obtained from human induced pluripotent cells in an environment with adenosine.
B and C: Osteoblast growth on a three-dimensional microporous matrix in a conventional culture medium (d-hiPSCs) and an adenosine medium (Ad-hiPSCs) and graft mineral density (the ratio of bone volume to total volume.
The size of the ruler is 2 mm.
Figure from an article in Science Advances – VM.
"It's amazing that a single molecule can determine the fate of stem cells," Varghese says in a university press release. "We don't need to use a cocktail of molecules, growth factors and other additives to create a population of bone cells from human induced pluripotent stem cells."
The study, published in Science Advances (Kang et al., Small molecule-driven direct conversion of human pluripotent stem cells into functional osteoblasts – VM), was a continuation of the previous work of the same team, during which scientists found that calcium phosphate isolated from bones helps stem cells differentiate into osteoblasts. Additional analysis showed that the cells use calcium phosphate to produce energy molecules of ATP, during the decay of which adenosine appears, which is necessary for the transformation of stem cells into bone cells.
"Then we wondered what would happen if we bypassed these steps and just added adenosine to the medium," Varghese explains.
Now the researchers will try to figure out exactly how these molecules trigger the process of cell transformation. So far, scientists assume that the A2bR receptor located on the stem cell membrane, which binds to adenosine, is involved in this.
According to the authors, the main goal of their work is to develop affordable methods of treating deformed and damaged bones using effective and inexpensive cellular engineering technologies.
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02.09.2016