Small intestinal submucosa-derived extracellular matrix bioscaffold significantly enhances angiogenic factor secretion from human mesenchymal stromal cells

Abstract

IntroductionThe 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.MethodsIn 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.ResultsWe 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.ConclusionsThis study demonstrates that MSCs transplanted onto a SIS ECM may greatly increase their therapeutic potential through an increase in pro-angiogenic cytokine release.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-015-0165-3) contains supplementary material, which is available to authorized users.

Diverse preparation methods for small intestinal submucosa (SIS): Decellularization, components, and structure

“…Small intestinal submucosa is widely used for tissue repair and regeneration, with benefits from its ECM functional components and structure . It is considered to positively modulate cell behaviors and induce vascularization for tissue repair and remolding . As a graft to be implanted into the body, most of the intrinsic cells of SIS need to be removed to avoid adverse immunogenic reactions.…”

“…3,4,29,30 It is considered to positively modulate cell behaviors and induce vascularization for tissue repair and remolding. 31,32 As a graft to be implanted into the body, most of the intrinsic cells of SIS need to be removed to avoid adverse immunogenic reactions. Therefore, it is necessary to completely decellularize SIS to prepare it for use.…”

Effect of bovine pericardial extracellular matrix scaffold niche on seeded human mesenchymal stem cell function

“…hMSC were isolated from fresh, unprocessed bone marrow from three healthy donors (Lonza, Allendale, NJ) and transduced with enhanced green fluorescent protein (eGFP) as previously described31. The pCCLc-MNDU3-LUC-PGK-EGFP-WPRE lentiviral vector was generated by the UC Davis Vector Core.…”

A review of decellurization methods caused by an urgent need for quality control of cell‐free extracellular matrix' scaffolds and their role in regenerative medicine

“…The applications of these biomaterials includes, for example, hernia reconstructive surgery, 26,27 soft tissue augmentation, breast reconstruction, 28,29 and wound healing. [30][31][32][33] The decellurization processes were subjected to a number of tissues, such as the submucosa, 34 the esophageal tissues, 35 those of the bladder, 36 the placenta, 37 the pericardium, 38 the heart valve 39,40 and the dermis. [30][31][32][33] They were also subjected to whole organs, such as the heart, 41 the liver, 42 the lungs, 43 the kidney, 44 and the central nervous system.…”