Human Adipose Derived Stem Cells (hASC's) and Soft Tissue Reconstruction: Evaluation of Methods for Increasing the Vascularity of Tissue Engineered Soft Tissue Construct

Persistent Link:
http://hdl.handle.net/10150/265352
Title:
Human Adipose Derived Stem Cells (hASC's) and Soft Tissue Reconstruction: Evaluation of Methods for Increasing the Vascularity of Tissue Engineered Soft Tissue Construct
Author:
Vijayasekaran, Aparna
Issue Date:
2012
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Generation of large volumes to cover an existing soft tissue defect is often complicated by the lack of available tissue. The current options for soft tissue reconstruction include local and free flaps, collagen fillers, traditional fat grafting and other synthetic soft tissue fillers. But they all have limitations. Recently, a lot of interest has been generated regarding the use of human adipose derived stem cells for engineering a biocompatible soft tissue construct. Give their ready availability, viability and plasticity they appear to be the ideal building blocks for a cell based soft tissue construct. We find that these cells are easy to isolate in large numbers, easy to maintain in culture and capable of multi-lineage differentiation. hASC's are readily adherent to collagen based scaffolds and these function as the ideal cell delivery matrix. Since most wound beds are ischemic and hypoxic, changes in gene expression of hASC's was studied in conditions of hypoxia and serum deprivation. Microarray PCR results demonstrate the up regulation of 23 angiogenic genes including VEGFC, ANPEP, CXCL6, ANGPLT4 and CXCL5 in conditions of hypoxia. However, this angiogenic response was blunted with the presence of serum starvation in addition to hypoxia. Hence we chose to investigate methods to increase the primary neovascularization of a tissue engineered construct. Our hypothesis was that Europium Nano rods (belonging to the lanthanide series of heavy metals) would increase the angiogenic potential of hASC's. Results of a chick embryo chorioallantoic membrane assay demonstrate that Europium Nano rods potentiate the angiogenic effects of Vascular Endothelial Growth Factor (VEGF) when incorporated in hASC's. These rods are readily incorporated in hASC's by endocytosis and do not affect viability. Hence, we conclude that Europium Nano rods can function as a reliable, nontoxic extrinsic angiogenic stimulus. Further studies are needed to evaluate the 1) effects of ENR's on stem cell plasticity 2) effects on gene expression and 3) further investigate the fate of ENR's with repeated cell division.
Type:
text; Electronic Thesis
Keywords:
Medical Sciences
Degree Name:
M.S.
Degree Level:
masters
Degree Program:
Graduate College; Medical Sciences
Degree Grantor:
University of Arizona
Advisor:
Rilo, Horacio

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleHuman Adipose Derived Stem Cells (hASC's) and Soft Tissue Reconstruction: Evaluation of Methods for Increasing the Vascularity of Tissue Engineered Soft Tissue Constructen_US
dc.creatorVijayasekaran, Aparnaen_US
dc.contributor.authorVijayasekaran, Aparnaen_US
dc.date.issued2012-
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractGeneration of large volumes to cover an existing soft tissue defect is often complicated by the lack of available tissue. The current options for soft tissue reconstruction include local and free flaps, collagen fillers, traditional fat grafting and other synthetic soft tissue fillers. But they all have limitations. Recently, a lot of interest has been generated regarding the use of human adipose derived stem cells for engineering a biocompatible soft tissue construct. Give their ready availability, viability and plasticity they appear to be the ideal building blocks for a cell based soft tissue construct. We find that these cells are easy to isolate in large numbers, easy to maintain in culture and capable of multi-lineage differentiation. hASC's are readily adherent to collagen based scaffolds and these function as the ideal cell delivery matrix. Since most wound beds are ischemic and hypoxic, changes in gene expression of hASC's was studied in conditions of hypoxia and serum deprivation. Microarray PCR results demonstrate the up regulation of 23 angiogenic genes including VEGFC, ANPEP, CXCL6, ANGPLT4 and CXCL5 in conditions of hypoxia. However, this angiogenic response was blunted with the presence of serum starvation in addition to hypoxia. Hence we chose to investigate methods to increase the primary neovascularization of a tissue engineered construct. Our hypothesis was that Europium Nano rods (belonging to the lanthanide series of heavy metals) would increase the angiogenic potential of hASC's. Results of a chick embryo chorioallantoic membrane assay demonstrate that Europium Nano rods potentiate the angiogenic effects of Vascular Endothelial Growth Factor (VEGF) when incorporated in hASC's. These rods are readily incorporated in hASC's by endocytosis and do not affect viability. Hence, we conclude that Europium Nano rods can function as a reliable, nontoxic extrinsic angiogenic stimulus. Further studies are needed to evaluate the 1) effects of ENR's on stem cell plasticity 2) effects on gene expression and 3) further investigate the fate of ENR's with repeated cell division.en_US
dc.typetexten_US
dc.typeElectronic Thesisen_US
dc.subjectMedical Sciencesen_US
thesis.degree.nameM.S.en_US
thesis.degree.levelmastersen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineMedical Sciencesen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorRilo, Horacioen_US
dc.contributor.committeememberMcDonagh, Paulen_US
dc.contributor.committeememberHeimark, Ronalden_US
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