Document Type
Article
Publication Date
10-2019
Publication Title
Journal of Tissue Engineering and Regenerative Medicine
Abstract
Myocardial infarction results in loss of cardiac cell types, inflammation, extracellular matrix (ECM) degradation, and fibrotic scar. Transplantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) is being explored as they could differentiate into cardiomyocyte-like cells, integrate into host tissue, and enhance resident cell activity. The ability of these cells to restore lost ECM, remodel the inflammatory scar tissue, and repair the injured myocardium remains unexplored. We here elucidated the synthesis and deposition of ECM (e.g., elastin, sulfated glycosaminoglycans, hyaluronan, collagen type III, laminin, fibrillin, lysyl oxidase, and nitric oxide synthases), matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), and other secretome (cytokines, chemokines, and growth factors) in adult human BM-MSC spheroid cultures within three-dimensional collagen gels. The roles of species-specific type I collagen and 5-azacytadine were assessed over a 28-day period. Results revealed that human collagen (but not rat-derived) suppressed MSC proliferation and survival, and MSCs synthesized and released a variety of ECM proteins and secretome over the 28 days. Matrix deposition is at least an order of magnitude lower than their release levels at every time point, most possibly due to elevated MMP levels and interleukins with a concomitant decrease in TIMPs. Matrix synthesis over the 28-day period was fitted to a competitive inhibition form of Michaelis-Menten kinetics, and the production and decay rates of ECM, MMPs, and TIMPs, along with the kinetic model parameters quantified. Such an integrated experimental and modelling approach would help elucidate the critical roles of various parameters (e.g., cell encapsulation and delivery vehicles) in stem cell-based transplantation therapies.
Repository Citation
Joshi, Jyotsna; Abnavi, Mohammadreza Dehghan; and Kothapalli, Chandrasekhar R., "Synthesis and Secretome Release by Human Bone Marrow Mesenchymal Stem Cell Spheroids within Three-dimensional Collagen Hydrogels: Integrating Experiments and Modelling" (2019). Chemical & Biomedical Engineering Faculty Publications. 164.
https://engagedscholarship.csuohio.edu/encbe_facpub/164
Volume
13
Issue
10
DOI
10.1002/term.2943
Version
Postprint
Publisher's Statement
This is the accepted version of the following article: Joshi, J, Abnavi, MD, Kothapalli, CR. Synthesis and secretome release by human bone marrow mesenchymal stem cell spheroids within three‐dimensional collagen hydrogels: Integrating experiments and modelling. J Tissue Eng Regen Med. 2019; 13, 1923– 1937. https://doi.org/10.1002/term.2943 , which has been published in final form at https://doi.org/10.1002/term.2943
Comments
C.K. expresses his gratitude to the Cleveland State University Office of Research funds, and J.J. thanks the financial support from the Cellular and Molecular Medicine Specialization Fellowship and Dissertation Research Award from Cleveland State University.