A practical analysis of adipose stromal cell functional differentiation response to multiple microenvironmental stimuli
Abstract
The cellular microenvironment composed in the extracellular matrix is immediately responsible for influencing cellular activities such as differentiation, morphology, migration, ECM synthesis, apoptosis, and cell proliferation. Microenvironmental modes that influence cell activity include: soluble stimuli such as β-glycerol phosphate, ascorbic acid, and fibroblast growth factor which can influence osteogenesis, ECM synthesis, and proliferation; ECM protein stimuli exemplified by collagen, fibronectin, and laminin existent on the ECM surface; as well as the scale and topographical morphology of stimuli on the ECM surface. Adipose stromal cells are multipotent stem cells showing significant differential capacity in response to microenvironmental stimuli while exhibiting practical attributes that surpass bone marrow stromal cells and embryonic stem cells. The advantages posed by adipose derived stem cells make them better candidates for research and clinical applications regarding cell based regenerative tissue engineering. In this dissertation, the singular and combined influences of soluble, protein, and topographical stimuli on the functional differentiation of ASCs seeded onto a three dimensional poly(lactic-co-glycolic acid) construct were compared, characterized and then evaluated for their utility in real world clinical regenerative tissue engineering applications. Functional differentiation in this dissertation is described as ECM synthesis by seeded cells and cell number, which are proxies of de novo tissue generation integral to tissue regeneration. The data indicate synergistic interaction a of nanoscale surface topography with other stimuli modulate ASC response to soluble and protein stimuli which results in ECM synthesis, cell numbers, and ECM synthesis outputs per cell that are distinct from ASC response to singularly applied stimuli. In some cases, the amount of ECM present per the cell number matches cell-ECM ratios existent in natural tissue profiles, indicating that modulating ASCs response to tissue constructs containing combinations of soluble, protein, and nanotopographical stimuli may be useful in the development of engineered tissue regenerative therapies.
Degree
Ph.D.
Advisors
Nauman, Purdue University.
Subject Area
Genetics|Cellular biology|Biochemistry|Biomedical engineering
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