Human Induced Pluripotent Stem Cells Recall Their Origins

Ordinary somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) capable of generating any cell type in the body, provided that a methodology is established to reliably guide the cells down that path of differentiation. This reprogramming is sufficiently straightforward that near any lab can carry it out, which has led to rapid progress in this part of the field in recent years: a lot of effort has focused on developing the means to create specific cell types from pluripotent cells. Why so much interest in the research community? Because a key part of the infrastructure needed for the coming decades of cell therapies, regenerative medicine, and tissue engineering is a low-cost, reliable source of any cell type desired, rapidly created to order from an easily obtained patient tissue sample such as skin or blood.

Induced pluripotency is currently the leading contender technology for wholesale production of patient-matched cells by virtue of ease of use, but it is not without its complexities. Here, for example, researchers show that the reprogramming of human cells isn't producing as much of a clean slate as might be expected based on work in mice:

[Researchers] have discovered that human stem cells made from adult donor cells "remember" where they came from and that's what they prefer to become again. This means the type of cell obtained from an individual patient to make pluripotent stem cells, determines what can be best done with them. For example, to repair the lung of a patient with lung disease, it is best to start off with a lung cell to make the therapeutic stem cells to treat the disease, or a breast cell for the regeneration of tissue for breast cancer patients. By contrast, the iPSCs of mice, which are widely used in stem cell research, have no memory. "So, if you only studied the mouse alone, you'd never uncover this opportunity."

"We've shown that human induced pluripotent stem cells have a memory that is engraved at the molecular/genetic level of the cell type used to make them, which increases their ability to differentiate to the parent tissue type after being put in various stem cell states. So, not all human iPSCs are made equal. Moving forward, this means that iPSC generation from a specific tissue requiring regeneration is a better approach for future cellular therapies. Besides being faster and more cost-efficient in the development of stem cell therapy treatments, this provides a new opportunity for use of iPSCs in disease modeling and personalized drug discovery that was not appreciated before."



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