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Stem Cell Res Ther. 2019 Nov 4;10(1):316. doi: 10.1186/s13287-019-1418-3.

Physiologic expansion of human heart-derived cells enhances therapeutic repair of injured myocardium.

Author information

1
University of Ottawa Heart Institute, Division of Cardiology, Department of Medicine, University of Ottawa, H3214 40 Ruskin Ave, Ottawa, ON, K1Y4W7, Canada.
2
Ottawa Hospital Research Institute, Division of Regenerative Medicine, Department of Medicine, University of Ottawa, Ottawa, K1H8L6, Canada.
3
University of Ottawa Heart Institute, Division of Cardiac Surgery, Department of Medicine, University of Ottawa, Ottawa, K1Y4W7, Canada.
4
University of Saskatchewan, Saskatoon, S7N 0W8, Canada.
5
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, K1H8M5, Canada.
6
Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, K1H8L6, Canada.
7
University of Ottawa Heart Institute, Division of Cardiology, Department of Medicine, University of Ottawa, H3214 40 Ruskin Ave, Ottawa, ON, K1Y4W7, Canada. ddavis@ottawaheart.ca.
8
Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, K1H8L6, Canada. ddavis@ottawaheart.ca.

Abstract

BACKGROUND:

Serum-free xenogen-free defined media and continuous controlled physiological cell culture conditions have been developed for stem cell therapeutics, but the effect of these conditions on the relative potency of the cell product is unknown. As such, we conducted a head-to-head comparison of cell culture conditions on human heart explant-derived cells using established in vitro measures of cell potency and in vivo functional repair.

METHODS:

Heart explant-derived cells cultured from human atrial or ventricular biopsies within a serum-free xenogen-free media and a continuous physiological culture environment were compared to cells cultured under traditional (high serum) cell culture conditions in a standard clean room facility.

RESULTS:

Transitioning from traditional high serum cell culture conditions to serum-free xenogen-free conditions had no effect on cell culture yields but provided a smaller, more homogenous, cell product with only minor antigenic changes. Culture within continuous physiologic conditions markedly boosted cell proliferation while increasing the expression of stem cell-related antigens and ability of cells to stimulate angiogenesis. Intramyocardial injection of physiologic cultured cells into immunodeficient mice 1 week after coronary ligation translated into improved cardiac function and reduced scar burden which was attributable to increased production of pro-healing cytokines, extracellular vesicles, and microRNAs.

CONCLUSIONS:

Continuous physiological cell culture increased cell growth, paracrine output, and treatment outcomes to provide the greatest functional benefit after experimental myocardial infarction.

KEYWORDS:

Adult progenitor cells; Cell manufacturing; Cell therapy; Heart failure

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