Biomedical Engineering News
08/17/2011
ABME Journal Highlight: Growing human tissue using adult stem cells could ease back pain
Fiber Stretch and Reorientation Modulates Mesenchymal Stem Cell Morphology and Fibrous Gene Expression on Oriented Nanofibrous Microenvironments
By: Su-Jin Heo, Nandan L. Nerurkar, Brendon M. Baker, Jung-Woog Shin, Dawn M. Elliott, and Robert L. Mauck
Using adult stem cells and ultra-fine nanofibers, researchers at the University of Pennsylvania and Inje University developed lab-grown tissue that could one day be used in patients suffering from back pain associated with disc degeneration, according to an article published in the August issue of the Annals of Biomedical Engineering journal.
One focus of regenerative medicine is the development of lab-grown tissues for the replacement of damaged or diseased tissues throughout the body. The type of tissue to be replaced dictates specific challenges that must be overcome if the engineered tissue is to match native tissue function.
For orthopaedic tissues in particular, this means that engineered materials must be able to operate and respond to a complex mechanical environment, where large forces are regularly experienced over a lifetime of daily activities. Nature has addressed this challenge through the evolution of organized multi-directional structures.
For instance, the aligned collagen in tendon is quite stiff in tension and so is well suited to transmit forces in one direction, from the muscle to the bone. Other tissues, such as the annulus fibrosus of the intervertebral disc (the soft segments of the spine), have a more complex structure, where highly organized (and alternating) layers of fibers confer strength and flexibility in many directions at once.
Our group recently developed methods for engineering replacements for the annulus fibrosus. The structure and mechanical properties of the tissue was recreated when adult stem cells were coupled with a specialized multi-layered scaffold consisting of organized, ultra-fine biodegradable nanofibers.
In the current study, we expanded this work to consider how stretching these engineered tissues influences cell shape and activity as a function of fiber structure. Cells within these materials will encounter stretch after being implanted in the spine, and these signals may influence maturation of the construct.
Here, we demonstrate that, in a single layer, cell and nuclear elongation and reorientation are coupled to the underlying fiber structure, and that reorientation occurs in a predictable fashion. Moreover, changes in cell shape resulted into changes in cell activity, with the magnitude and duration of the biologic response depending on the initial fiber orientation. This suggests that directional cues, together with mechanical loading, will influence the growth and maturation of engineered constructs when they are implanted.
This study also furthers our understanding of how mechanical loading may influence stem cell differentiation and function. Ultimately, this work may one day provide clinical solutions via tissue engineering with stem cells for the large patient population suffering from back pain associated with disc degeneration.