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" Focused in vivo combinatorial analysis of nano-labeled engineered myofascial constructs utilizing adult stem cells "
John Thomas Propst
M. J. F. Yost, Stephen A.
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Latin Dissertation
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English
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| Record Number
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53904
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TL23858
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| Call number
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3336617
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| Main Entry
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John Thomas Propst
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| Title & Author
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Focused in vivo combinatorial analysis of nano-labeled engineered myofascial constructs utilizing adult stem cells\ John Thomas Propst
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| College
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University of South Carolina
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| Date
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2008
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| Degree
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Ph.D.
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2008
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| Page No
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275
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| Abstract
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Ever since the earliest cavemen was mauled by a mammoth, stabbed by a flint-headed spear or burned by a stone age cooking fire, men and women have fought to heal wounds. We have records of wound care that trace back to ancient Egypt and Greece, circa 1500 BC. Today, patients and healthcare professionals are faced with the overwhelming and costly consequence of losing functional organs and tissues. Attempts to generate bio-artificial tissues and organs to ameliorate human disease date as far back as 30 years. However, engineered tissues have not had wide acceptance in clinical applications because they previously have not been able to utilize the vascular beds into which they were transplanted. Upon tissue loss or damage in higher vertebrate adult animals most organs fail to regenerate, rather they undergo a fibro-proliferative response, which develops into a fibrotic scar. Therefore, tissues are not regenerated, but patched--this method works well when wounds are small, however with larger wounds function is lost or impaired by the development of scar tissue. In an effort to overcome these biological roadblocks and contribute to the evolution of surgery, we have developed a novel tissue engineered repair system. This system combines the principles of engineering and the life sciences in an effort to develop a vascularized and regenerative skeletal muscle tissue repair. The ultimate goal of this technology is to restore complete function to an area once void of muscle tissue. Briefly, the model consists of a novel aligned collagen scaffold seeded with adult stem cells (satellite cells) for use in a surgically created ventral hernia. We have previously reported on the following observations: (1) significant transplanted skeletal muscle cell mass within the engineered repair compared to controls, (2) the integration of neomyofibers with adjacent native tissue, and (3) the ability of the engineered muscle to repair the hernia. In the current study, we present immunohistochemical and tri-chrome micrographs supporting the ability of this model system to naturally generate more neomyofibers and vascular structures in vivo than controls. We also test the hypothesis that the wound healing and angiogenic genetic profiles are significantly and temporally different between each repair model. To test this hypothesis, we have examined biopsies obtained along the repair interface via focused DNA microarrays, immunoassays, histology and immunohistochemistry. At this juncture, we present our in vivo investigation into transcriptional regulation of inflammatory mediators relevant to wound healing. Transcriptional changes were detected within two hours, with statistically significant differences (p<0.05) between treatments and controls. Approximately, 30% of relevant genes examined were expressed at significantly different levels (>100 fold; p<0.05), with genes encoding proteins involved in inflammatory response becoming active first.
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| Subject
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Health and environmental sciences; Applied sciences; Angiogenesis; Satellite cells; Skeletal muscle; Tissue engineering; Ventral hernia; Wound healing; Myofascial constructs; Stem cells; Biomedical engineering; Medicine; 0541:Biomedical engineering; 0564:Medicine
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M. J. F. Yost, Stephen A.
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University of South Carolina
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