A fundamental characteristic of immune cells is their capacity to interact and form signaling networks with each other, as this ability is essential for providing a timely and comprehensive immune response. Human embryonic stem cells (hESC) and induced pluripotent stem cells (iPSC) have been shown to have the potential to differentiate into a number of different cell types, including the blood cells involved in the immune response. However, the functional properties of those cells, including their ability interact and communicate with each other, have never been fully evaluated. Hence, the goal of our proposal is to establish whether the hESC/iPSC-derived immune cells have the capacity to interact and form signaling networks with each other in a physiological manner necessary to generate a functional immune response. This is an important basic science question as it closely evaluates the quality of the cellular differentiation process of hESC and iPSC into functional immune cells, providing insights into hematopoietic developmental pathways of hESC/iPSC. In addition, if functional abnormalities in hESC/iPSC-derived cells are observed, the wealth of information we will obtain in our work will provide a starting point to investigate this issue and may help us to design strategies to correct such defects.
Statement of Benefit to California:
Hematopoietic stem cell therapies have been used for the last fifty years for different medical treatments in California and throughout the world. The research on human embryonic stem cells (hESC) and induced pluripotent stem cells (iPSC) has created a substantial excitement in medical community, as these cells for several technical reasons may even be better suited for some of these therapies. However, a number of questions regarding hESC and iPSC need to be addressed before they can be moved to the clinic. Our research proposal examines very closely one of those issues. Namely, we seek to establish whether the hESC and iPSC-derived immune cells have the ability to interact and communicate with each other in a functional manner, which is a major prerequisite for an effective immune response. Hence, in this matter, our work will help establish whether hESC/iPSC-derived cells are really suitable for reconstitution of functional blood lineages. If not, the wealth of data we will obtain in the process may help us correct the problem. Therefore, this project may accelerate clinical application of hESC and iPSC leading to better hematopoietic therapies. New and better treatments for blood disorders or hematopoietic stem cell replacement therapies are certainly going to benefit the people of California.