Small intestinal submucosa-derived extracellular matrix bioscaffold significantly enhances angiogenic factor secretion from human mesenchymal stromal cells.
BACKGROUND
The in vivo therapeutic effect of mesenchymal stromal cells (MSCs) is currently believed to be tightly linked to their paracrine secretion ability. However, insufficient or imprecise cell delivery, low cell survival and retention post-transplant, along with harsh donor site microenvironments, are major barriers to the clinical success of MSC therapies. Here we tested a small intestinal submucosa (SIS)-derived extracellular matrix (ECM) bioscaffold augmented with MSCs, with the hypothesis that they will facilitate the precise delivery of increased numbers of MSCs therefore improving cell viability and retention.


METHODS
In this study, we evaluated the secretion of angiogenic factors from three human MSC lines cultured on SIS ECM. We used human antibody array and enzyme-linked immunosorbent assay to measure the level of angiogenic factors released from MSCs when cultured on SIS ECM or regular tissue culture plastic. We tested MSCs cultured for three different time points.


RESULTS
We found that the SIS ECM culture environment can significantly enhance the release of several angiogenic factors when compared to MSCs cultured on standard tissue culture plastic. Specifically, vascular endothelial growth factor and interleukin-8 secretion was significantly increased at 24, 48 and 72 hours postseeding onto SIS ECM whereas vascular endothelial growth factor release for cells cultured on plastic surface remained the same during these time points. We also observed significant donor to donor variation in cytokine production.


CONCLUSIONS
This study demonstrates that MSCs transplanted onto a SIS ECM may greatly increase their therapeutic potential through an increase in pro-angiogenic cytokine release.
Department of Surgery, UC Davis Medical Center, Sacramento, CA, USA. xinlin@ucdavis.edu.
Xin
X
Lin
Department of Surgery, UC Davis Medical Center, Sacramento, CA, USA. mbrobinson@ucdavis.edu.
Mikella
M
Robinson
Department of Surgery, UC Davis Medical Center, Sacramento, CA, USA. tyepetrie@ucdavis.edu.
Tye
T
Petrie
Department of Surgery, UC Davis Medical Center, Sacramento, CA, USA. vgs27@humboldt.edu.
Veronica
V
Spandler
Department of Surgery, Division of Cardiothoracic Surgery, UC Davis Medical Center, Sacramento, CA, USA. wdboyd@ucdavis.edu.
W Douglas
WD
Boyd
Department of Surgery, Division of Cardiothoracic Surgery, UC Davis Medical Center, Sacramento, CA, USA. cssondergaard@ucdavis.edu.
Claus Svane
CS
Sondergaard
D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D054457:Tissue Scaffolds
D043925:Angiogenesis Inducing Agents; D017077:Culture Media, Conditioned