Hypoxic Conditions Promote the Angiogenic Potential of Human Induced Pluripotent Stem Cell-Derived Extracellular Vesicles

International Journal of Molecular Sciences, 2021 · DOI: 10.3390/ijms22083890 · Published: April 9, 2021

Cardiovascular Science Regenerative Medicine Genetics

Simple Explanation

Stem cells communicate by releasing extracellular vesicles (EVs) that can help regenerate injured tissues. This study explores if growing human induced pluripotent stem cells (iPSCs) in low oxygen (hypoxia) affects the quantity, quality, and ability of their EVs to promote blood vessel formation (angiogenesis). The study found that iPSC-EVs produced in low oxygen conditions (1%) had a significantly greater potential to stimulate angiogenesis than those produced in higher oxygen conditions. These EVs were also more effective than the soluble factors secreted by the cells. The researchers conclude that carefully selecting cell culture conditions and EV preparation methods can improve the production of potent iPSC-EVs for therapeutic applications.

Study Duration

Not specified

Participants

Umbilical cord blood and bone marrow stromal cells

Evidence Level

In vitro study

Key Findings

1
iPSC-EVs derived from 1% oxygen culture exhibit significantly elevated angiogenic potential compared to EVs obtained at higher oxygen levels.
2
Tangential flow filtration (TFF) yields superior EV recovery compared to ultracentrifugation (TUCF).
3
Hypoxic conditioning of human iPSCs results in the secretion of iPSC-EVs that are significantly more potent than corresponding soluble factors in inducing vascular network formation in vitro.

Research Summary

This study demonstrates that both cell culture oxygen conditions and the mode of EV preparation significantly affect the function of human iPSC-EVs. Hypoxic conditioning of human iPSCs resulted in the secretion of iPSC-EVs with significantly elevated angiogenic potential compared to corresponding soluble factors. Selecting appropriate protocols will further improve the production of particularly potent iPSC-EV-based therapeutics.

Practical Implications

Therapeutic Potential

Hypoxia-conditioned iPSC-EVs could be a potent cell-free therapeutic approach for regenerative medicine, particularly in promoting angiogenesis in ischemic tissues.

Manufacturing Considerations

The study highlights the importance of optimizing cell culture conditions (oxygen levels) and EV isolation methods (TFF vs. TUCF) to maximize the therapeutic potential of iPSC-EVs.

Further Research

Future studies should focus on identifying the specific molecular mechanisms (e.g., specific proteins or microRNAs) responsible for the enhanced angiogenic properties of hypoxia-conditioned iPSC-EVs.

Study Limitations

1
The analysis of the molecular mechanisms underlying the pro-angiogenic effects of iPSC-EVs obtained during hypoxic iPSC culture is still pending.
2
The study did not address the question whether small exomeres may reside within the soluble factor fraction.
3
Based on these data we can just speculate that hypoxia-induced proteins contribute to the observed effect.

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