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Pluripotent Stem Cell Derived Cardiac Cells for Myocardial Repair
Published on: February 3, 2017
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Brachyury engineers cardiac repair competent stem cells
Mark Li1,2, Satsuki Yamada1,3, Ao Shi1,4
1Center for Regenerative Medicine, Van Cleve Cardiac Regenerative Medicine Program, Marriott Heart Disease Research Program, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Stem Cells Translational Medicine
|October 24, 2020
Summary
A novel method uses modified messenger RNA (mRNA) to engineer stem cells for heart repair. This approach enhances stem cell antioxidant, blood vessel-forming, and immune-modulating properties, improving cardiac function after heart attack.
Area of Science:
- Regenerative Medicine
- Stem Cell Biology
- Cardiovascular Research
Background:
- Current stem cell enhancement protocols for heart failure are resource-intensive.
- Optimizing stem cell regenerative capacity is crucial for treating ischemic heart failure.
Purpose of the Study:
- To develop a streamlined method for enhancing stem cells for cardiac repair.
- To engineer human adipose-derived mesenchymal stem cells (AMSCs) into cardiopoietic stem cells (eCP) using a protein-independent approach.
Main Methods:
- Application of microencapsulated-modified-mRNA (M³ RNA) technology to introduce early cardiogenic genes into AMSCs.
- Utilizing a single transcription factor, Brachyury, to induce expression of cardiopoietic markers (Nkx2.5, Mef2c).
- In vitro and in vivo assessments of engineered cardiopoietic stem cells (eCP) in a murine myocardial infarction model.
Main Results:
- A single gene manipulation with Brachyury successfully triggered high expression of key cardiopoietic markers.
- Engineered cardiopoietic stem cells (eCP) exhibited enhanced antioxidant capacity, a vasculogenic secretome, and immunomodulatory properties.
- In vivo studies demonstrated improved cardiac performance and protection against heart failure in a myocardial infarction model.
Conclusions:
- Protein-independent single gene manipulation via M³ RNA is an effective strategy for engineering heart repair-competent stem cells.
- The engineered stem cells possess a combination of antioxidant, vasculogenic, and immunomodulatory traits beneficial for cardiac regeneration.
- This approach expands the regenerative toolkit for treating heart failure.
