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Biotechnol J. 2017 Sep;12(9). doi: 10.1002/biot.201600732. Epub 2017 Aug 22.

Differences in Stem Cell Processing Lead to Distinct Secretomes Secretion-Implications for Differential Results of Previous Clinical Trials of Stem Cell Therapy for Myocardial Infarction.

Author information

1
Internal Medicine II, Department of Cardiology, Paracelsus Medical University Salzburg, Salzburg, Austria.
2
Ludwig Boltzmann Cluster for Cardiovascular Research, Department for Biomedical Research, Medical University Vienna, Vienna, Austria.
3
Internal Medicine III, Department of Oncology, Paracelsus Medical University Salzburg, Salzburg, Austria.
4
Department of Anesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Vienna, Austria.
5
Universitätsherzzentrum Thüringen, Clinic of Internal Medicine I, Department of Cardiology, Friedrich Schiller University Jena, Jena, Germany.
6
Division of Cardiology, Pulmonology, and Vascular Medicine University Duesseldorf, Medical Faculty, Duesseldorf, Germany.

Abstract

Stem cell therapy for acute myocardial infarction (AMI) seemed to be a promising therapy, however, large clinical trials brought differential outcome. It has been shown that paracrine effects of secretomes of stem cells rather than cell therapy might play a fundamental role. The present study seeks to compare cell processing protocols of clinical trials and investigate effects of differential cell culture conditions on chemokine secretion and functional effects. Different secretomes are compared regarding IL-8, VEGF, MCP-1, and TNF-alpha secretion. Secretome mediated effects are evaluated on endothelial cell (HUVEC) tube formation and migration. Cardioprotective signaling kinases in human cardiomyocytes are determined by Western immunoblotting. Cells processed according to the REPAIR-AMI protocol secrete significantly higher amounts of IL-8 (487.3 ± 1231.1 vs 9.1 ± 8.2 pg mL-1 ; p < 0.05). REAPIR-AMI supernatants lead to significantly pronounced tube formation and migration on HUVEC and enhance the phosphorylation of Akt, ERK, and CREB. Cell processing conditions have a major impact on the composition of the secretome. The REPAIR-AMI secretome significantly enhances proangiogenic chemokine secretion, angiogenesis, cell migration, and cardioprotective signaling pathways. These results might explain differential outcomes between clinical trials. Optimizing cell processing protocols with special regards to paracrine factors, might open a new therapeutic concept for improving patient outcome.

KEYWORDS:

ASTAMI; REPAIR-AMI; angiogenesis; clinical trials; myocardial infarction; paracrine factors; signaling

PMID:
28731525
DOI:
10.1002/biot.201600732
[Indexed for MEDLINE]

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