iPSC-MSC-Mediated CAF Reprogramming in Pancreatic Cancer Therapy

School of Basic Medical Sciences, Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang, Hebei 050000, China

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Abstract

The dense microenvironment of pancreatic cancer is a key factor leading to treatment resistance and poor prognosis. Among the various cellular components of the microenvironment, cancer-associated fibroblasts(CAFs)play a particularly important role. This article systematically reviews the existing literature, focusing on the cancer-promoting mechanism of CAF, the advantages of induced pluripotent stem cell-derived mesenchymal stem cells(iPSC-MSCs)as a regulatory tool, and the four core mechanisms involved in CAFs reprogramming. CAFs promote tumor development mainly by constructing physical barriers, regulating cell signaling pathways, and mediating immune escape. The new tool iPSC-MSCs has the advantages of strong targeting homing ability, low immunogenicity and stable source, and is an ideal carrier for mediating CAFs reprogramming. It is currently believed that CAFs reprogramming can exert anti-tumor effects through the following four mechanisms: secretome regulation, exosome regulation, glycolipid metabolism reprogramming, and epigenetic reprogramming. By combing the above mechanisms, iPSC-MSCs-mediated targeted CAFs reprogramming is expected to become a promising strategy for interfering with the microenvironment of pancreatic cancer.