Date of Award

2011

Degree Type

Thesis

Degree Name

Master of Science

Program

Anatomy and Cell Biology

Supervisor

Dr. Victor K. M. Han

Abstract

Insulin-like growth factor binding protein-6 (IGFBP-6), a component of the stem cell niche involved in the differentiation of skeletal muscle myogenesis, is expressed in developing muscle cells and is the main regulator of IGF-II. In this study, I investigated the role of IGFBP-6 in the commitment of skeletal muscle derivation from placenta mesenchymal stem cells (PMSCs). I hypothesized that IGFBP-6 inhibits the temporal maintenance of PMSCs and promotes the differentiation of PMSCs into muscle via both extracellular and intracellular mechanisms. PMSCs can differentiate into muscle cells expressing the muscle markers Pax3/7, MyoD, and Myogenin with the formation of multi-nucleated fibers. Under differentiation conditions, silencing IGFBP-6 increased Pax3/7 and decreased OCT4 levels. In contrast, under non-differentiation conditions, there was a significant increase in Pax3/7 levels at day 7 with intracellular and extracellular increase of IGFBP-6, similarly silencing IGFBP-6 under non-differentiation conditions significantly increased Pax3/7 at 24 hours and decreased OCT4 levels over time same as in differentiation conditions. I concluded that increasing lGFBP-6 promotes PMSCs differentiation with more prominent effects at the beginning of the differentiation process, while silencing IGFBP-6 has more dramatic effects on PMSCs. Knowledge of the effects of IGFBP-6 on muscle differentiation will help improve strategies for skeletal muscle regeneration therapies using stem cells.

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.