Classical cell culture conditions are static while the natural physiological environment of living cells is mechanically active. Being at the helm of differentiation pathways; responsible for replenishment; repair and sustaining of major life processes; makes the micro-environment and differentiation pathways for stem cells particularly important to be under tight and narrow checkpoints. In addition to growth factors and chemical signals, the differentiation stages of cells are regulated through physical forces, extracellular matrix components and cell-to-cell interactions. Recently Saha1 et al showed clear evidence for control of human embryonic stem cell (hESC) differentiation under mechanical strain. Conditions were established that accomplished 1) passage of stem cells was made possible while differentiation was reduced, 2) self-renewal was promoted without selecting against survival of differentiated or undifferentiated cells, 3) stem cells retained pluripotency as evidenced by their ability to differentiate to cell lineages in all three germ layers, 4) application of mechanical forces may be useful, in combination with chemical and matrix-encoded signals, towards controlling differentiation of hESCs for therapeutic applications.

In other studies, human mesenchymal stem cells (hMSC), human adipose-derived adult stem cells (hADAS), or human processed lipoaspirate (PLA) cells were induced along several mesodermal lineages including fat, muscle, bone, and cartilage (reviewed by Estes² et al).

In solid tissue, cells migrate or are anchored on a mechano-transduction scaffold which connects extracellular matrix (ECM) components, to trans-membrane proteins often linked to intracellular microfilaments. The microfilaments transfer forces into the cells across signal transduction pathways often through microtubules governing overall natural gene expression. Microarray studies have shown that under proper mechanical strain, natural cellular growth is possible^3-10. Many examples of proper modulation of differentiation of progenitor cells have also been shown in tissue culture subjected to mechanical strain^11-12.

While mechanical strain governs these natural processes, mechanical stress is often the result or at times the cause of most pathologies as exemplified from associated loss of tissue architecture and cellular morphology. A better understanding of all of these processes and considerations of modulating the tensegrity forces can not only lead into proper studies of living cells under conditions simulating nature but can identify and target the appropriate targets for treatment.