Home Cell Biology RNA-based Reprogramming of Human Primary Fibroblasts into Induced Pluripotent Stem Cells
Cell Biology JoVE (Open Access) Citable · DOI

RNA-based Reprogramming of Human Primary Fibroblasts into Induced Pluripotent Stem Cells

DOI: 10.3791/58687-v
What you'll learn
  • Reprogram human primary fibroblasts into iPSCs using modified mRNA and microRNA mimics
  • Assess reprogramming efficiency and identify pluripotency markers like TRA-1-60
  • Expand clonal iPSC colonies from reprogrammed cells in feeder-free culture
Protocol

Biopharma Insights Here we describe a clinically relevant, high-efficiency, feeder-free method to reprogram human primary fibroblasts into induced pluripotent stem cells using modified mRNAs encoding reprogramming factors and mature microRNA-367/302 mimics. Also included are methods to assess reprogramming efficiency, expand clonal iPSC colonies, and confirm expression of the pluripotency marker TRA-1-60.

Difficulty
advanced
Total time
~2–4 weeks (from initial fibroblast plating to clonal iPSC expansion and characterization)
Model organism
Human primary fibroblasts
Biosafety
BSL-1

Steps

1
Prepare reagents for reprogramming protocol

Prepare modified mRNA encoding reprogramming factors, mature microRNA-367/302 mimics, and culture media. Ensure all reagents are thawed and ready for cell transfection.

▶ 00:45
2
Plate human primary fibroblasts for reprogramming

Seed human primary fibroblasts at appropriate density on culture plates in feeder-free conditions on Day 0. Establish baseline cultures for reprogramming induction.

▶ 02:01
3
Initiate reprogramming with mRNA and microRNA mimics

On Day 1, transfect fibroblasts with modified reprogramming factor mRNAs and microRNA-367/302 mimics. Monitor cells for morphological changes and early reprogramming markers.

▶ 05:09
4
Assess reprogramming efficiency and pluripotency

Evaluate reprogramming efficiency through colony formation analysis and confirm pluripotency marker expression (TRA-1-60) using immunofluorescence or flow cytometry. Expand clonal iPSC colonies.

▶ 09:28
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