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Summary: A need to identify a stem cell source for human endothelial colony forming cells (ECFCs) and mesenchymal stem cells (MSCs) that is high yield is crucial for their implementation in ischemia. Our lab has developed an isolation protocol to do this using full-term human villous placental tissue. This protocol describes enzymatic tissue digestion followed by MACS and FACS, achieving an 8 times greater yield versus traditional isolation techniques and delivering pure fetal stem cell colonies within 21–28 days cell culture.For complete details on the use and execution of this protocol, please refer to Patel et al. (2013) and Patel et al. (2014).