Systems biology approach to developing S2RM-based “systems therapeutics” and naturally induced pluripotent stem cells

Figure 1 General model of wound healing. The wounded state sends a homing signal to bone marrow stem cells and disrupts the ECM. Disruption of the ECM will shift the dynamic transition of potency towards dedifferentiation and the more pluripotent state. The more pluripotent state will cause the cells to proliferate. After proliferation, the migration of bone marrow stem cells to the wound site will release stem cell released molecules, including GDF-11, that stops proliferation and induces differentiation allowing newly differentiated somatic cells to repair the tissue. Thus, in our model, GDF11 is released from BMSCs and is a master regulator of stem cell transcription that inhibits cell proliferation and migration by down-regulating the expression of numerous genes involved in both these processes[93]. ECM-D: Extracellular matrix disruption; SC: Somatic cell; PPSC: Pluripotent stem cell; BMSC: Bone marrow stem cell; PSC: Potent stem cell.