Are purified or expanded cord blood-derived CD133+ cells better at improving cardiac function?
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Published on: June 18, 2018
Alexandra C Senegaglia1, Laura A Barboza, Bruno Dallagiovanna
1Pontifícia Universidade Católica do Paraná, Institute for Health and Biological Sciences, Rua Imaculada Conceição, 1155 Curitiba, Paraná, 80215901, Brazil. alexandra.senegaglia@pucpr.br
Insights
Human umbilical cord blood-derived CD133+ cells can be purified and expanded for treating myocardial infarction (MI). Both purified and expanded cells improved heart function in a rat MI model, showing therapeutic potential.
Area of Science:
- Regenerative Medicine
- Cardiovascular Biology
- Stem Cell Therapy
Background:
- Endothelial progenitor cells (EPCs) expressing CD133 are crucial for angiogenesis but are deficient in high-risk cardiovascular patients.
- Myocardial infarction (MI) leads to tissue damage that normal angiogenesis cannot repair.
- Human umbilical cord blood (HUCB)-derived EPCs offer a potential solution for impaired stem cell function in vulnerable populations.
Purpose of the Study:
- To purify and expand CD133+ cells from HUCB.
- To assess the efficacy of these cells in a rat model of MI.
- To evaluate their potential for cellular cardiomyoplasty.
Main Methods:
- CD133+ cells were isolated from HUCB using magnetic microbeads.
- Cells were expanded in vitro with growth factors and characterized for EPC and mature endothelial cell (EC) markers.
- The therapeutic effect was evaluated by intramyocardial injection into rats with induced MI.
Main Results:
- Purified CD133+ cells expressed EPC markers, while expanded cells showed mature EC markers and formed tubule-like structures.
- Expanded cells expressed VEGF mRNA and retained functional activity after 70-fold expansion over 60 days.
- Both purified and expanded CD133+ cells significantly improved left ventricular ejection fraction in the rat MI model.
Conclusions:
- CD133+ cells from HUCB can be effectively purified and expanded in vitro while maintaining biological activity.
- Both purified and expanded CD133+ cells demonstrate promising therapeutic potential for MI treatment via cellular cardiomyoplasty.
- Further pre-clinical studies are warranted to compare the clinical advantages of expanded versus purified CD133+ cells.
Abstract:
Endothelial progenitor cells (EPCs), which express the CD133 marker, can differentiate into mature endothelial cells (ECs) and create new blood vessels. Normal angiogenesis is unable to repair the injured tissues that result from myocardial infarction (MI). Patients who have high cardiovascular risks have fewer EPCs and their EPCs exhibit greater in vitro senescence. Human umbilical cord blood (HUCB)-derived EPCs could be an alternative to rescue impaired stem cell function in the sick and elderly. The aim of this study was to purify HUCB-derived CD133(+) cells, expand them in vitro and evaluate the efficacy of the purified and expanded cells in treating MI in rats. CD133(+) cells were selected for using CD133-coupled magnetic microbeads. Purified cells stained positive for EPC markers. The cells were expanded and differentiated in media supplemented with fetal calf serum and basic fibroblast growth factor, insulin-like growth factor-I and vascular endothelial growth factor (VEGF). Differentiation was confirmed by lack of staining for EPC markers. These expanded cells exhibited increased expression of mature EC markers and formed tubule-like structures in vitro. Only the expanded cells expressed VEGF mRNA. Cells were expanded up to 70-fold during 60 days of culture, and they retained their functional activity. Finally, we evaluated the therapeutic potential of purified and expanded CD133(+) cells in treating MI by intramyocardially injecting them into a rat model of MI. Rats were divided into three groups: A (purified CD133(+) cells-injected); B (expanded CD133(+) cells-injected) and C (saline buffer-injected). We observed a significant improvement in left ventricular ejection fraction for groups A and B. In summary, CD133(+) cells can be purified from HUCB, expanded in vitro without loosing their biological activity, and both purified and expanded cells show promising results for use in cellular cardiomyoplasty. However, further pre-clinical testing should be performed to determine whether expanded CD133(+) cells have any clinical advantages over purified CD133(+) cells.
