Seeking possible ways to create replacement cells for the faded ones with deficits in functionality or quantity inspires comprehensive needs for cell lineage conversion. To fulfill this promise, reprogramming and microenvironment direction have been used to manipulate abundant cell fates. We briefly describe the evolution and fundamental insights of these two major strategies applied for lineage specification, comment generally on their current limitations, and analyze the orchestral interplay between them. We also present several future directions and discuss the potential clinical uses. Based on the relatively slight safety and technical issues, we conclude that microenvironment-evoked cell lineage conversion, instead of reprogramming, will be the shifting focus in regenerative medicine.
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