國立虎尾科技大學 |

Development of an Angiogenic Tissue-on-a-Chip Microenvironment.

紀錄類型:	書目-語言資料,手稿 : Monograph/item
正題名/作者:	Development of an Angiogenic Tissue-on-a-Chip Microenvironment./
作者:	Stuehr, Eric.
面頁冊數:	1 online resource (107 pages)
附註:	Source: Masters Abstracts International, Volume: 85-06.
Contained By:	Masters Abstracts International85-06.
標題:	Cellular biology. -
電子資源:	click for full text (PQDT)
ISBN:	9798380863124

Development of an Angiogenic Tissue-on-a-Chip Microenvironment.
Stuehr, Eric.

Development of an Angiogenic Tissue-on-a-Chip Microenvironment. - 1 online resource (107 pages)

Source: Masters Abstracts International, Volume: 85-06.

Thesis (M.S.)--California Polytechnic State University, 2023.

Includes bibliographical references

Preclinical testing is necessary to investigate the safety and efficacy of novel therapeutics before moving to clinical trials, yet approximately 90% of these therapies fail once tested in humans. This has led to increased interest in developing robust preclinical models that accurately mimic the complex human in vivo physiology. Microfluidic devices that can introduce dynamic conditions to 3D cell/organoid cultures, also known as tissue-on-a-chip, have emerged as physiologically relevant in vitro preclinical models that can achieve high throughput screening of therapeutics. The research presented here aimed to develop an angiogenic environment within a novel microfluidic device to stimulate formation of endothelial networks that will eventually be integrated into a vascularized tumor model for screening chemotherapeutics. The novel microfluidic devices were fabricated using photolithography to create a patterned mold, casting polydimethylsiloxane (PDMS) over the mold, and bonding patterned PDMS to a glass slide. Three sets of experiments were then conducted, with each introducing different angiogenic stimuli to human umbilical vein endothelial cells (HUVECs) co-cultured with human dermal fibroblasts (HDFs) within the devices. The first set of experiments sought to develop a standard protocol for plating human cells in the novel microfluidic device and to investigate if the mechanism of nutrient transport and interstitial flow would induce an angiogenic response resulting in endothelial network formation. A working protocol was developed but it was determined that further development of an angiogenic environment within the device was necessary to stimulate endothelial network formation. The second set of experiments investigated if seeding HUVECs in a peripheral channel of the device and introducing a concentration gradient of vascular endothelial growth factor (VEGF) would stimulate endothelial network formation directed by a growth factor gradient, similar to angiogenesis in vivo. This was repeated under hypoxic conditions to more accurately mimic the in vivo angiogenic environment, but significant endothelial network formation was not observed and seeding of HUVECs in the peripheral channel presented no perceptible improvements. The final set of experiments investigated if returning HUVECs to the center chamber in local co-culture with HDFs and exposing devices to hypoxic conditions would provide the necessary angiogenic environment to stimulate endothelial network formation within the microfluidic device. Lack of quantifiable endothelial network formation in the final set of experiments led to an analysis of 3D HUVEC colony formation, however, no statistically significant trends were discovered. Even though no significant differences were found, these experiments succeeded in developing a protocol for plating human cells in the novel microfluidic device that can be translated to the tumor side of the Microphysiological Systems lab. From these experiments we can also conclude that co-cultures of HUVECs and HDFs can survive and form into colonies within the novel microfluidic device but additional angiogenic stimuli are necessary to develop robust endothelial networks. Based on the current literature and knowledge gained throughout the experiments presented here, several suggestions are presented to potentially stimulate angiogenesis and develop endothelial networks in the device such as increasing cell densities, varying length of incubation, introducing mediators of angiogenesis like nitric oxide, and addition of tumor cells.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2024

Mode of access: World Wide Web

ISBN: 9798380863124Subjects--Topical Terms:

1148666
Cellular biology.
Subjects--Index Terms:

Tumor cellsIndex Terms--Genre/Form:

554714
Electronic books.

Development of an Angiogenic Tissue-on-a-Chip Microenvironment.
LDR:04981ntm a22003977 4500 001 1149408
005 20241015112546.5
006 m o d
007 cr bn ---uuuuu
008 250605s2023 xx obm 000 0 eng d
020 $a 9798380863124
035 $a (MiAaPQ)AAI30973856
035 $a (MiAaPQ)CalPoly4381
035 $a AAI30973856
040 $a MiAaPQ $b eng $c MiAaPQ $d NTU
100 1 $a Stuehr, Eric. $3 1475630
245 1 0 $a Development of an Angiogenic Tissue-on-a-Chip Microenvironment.
264 0 $c 2023
300 $a 1 online resource (107 pages)
336 $a text $b txt $2 rdacontent
337 $a computer $b c $2 rdamedia
338 $a online resource $b cr $2 rdacarrier
500 $a Source: Masters Abstracts International, Volume: 85-06.
500 $a Advisor: Heylman, Christopher.
502 $a Thesis (M.S.)--California Polytechnic State University, 2023.
504 $a Includes bibliographical references
520 $a Preclinical testing is necessary to investigate the safety and efficacy of novel therapeutics before moving to clinical trials, yet approximately 90% of these therapies fail once tested in humans. This has led to increased interest in developing robust preclinical models that accurately mimic the complex human in vivo physiology. Microfluidic devices that can introduce dynamic conditions to 3D cell/organoid cultures, also known as tissue-on-a-chip, have emerged as physiologically relevant in vitro preclinical models that can achieve high throughput screening of therapeutics. The research presented here aimed to develop an angiogenic environment within a novel microfluidic device to stimulate formation of endothelial networks that will eventually be integrated into a vascularized tumor model for screening chemotherapeutics. The novel microfluidic devices were fabricated using photolithography to create a patterned mold, casting polydimethylsiloxane (PDMS) over the mold, and bonding patterned PDMS to a glass slide. Three sets of experiments were then conducted, with each introducing different angiogenic stimuli to human umbilical vein endothelial cells (HUVECs) co-cultured with human dermal fibroblasts (HDFs) within the devices. The first set of experiments sought to develop a standard protocol for plating human cells in the novel microfluidic device and to investigate if the mechanism of nutrient transport and interstitial flow would induce an angiogenic response resulting in endothelial network formation. A working protocol was developed but it was determined that further development of an angiogenic environment within the device was necessary to stimulate endothelial network formation. The second set of experiments investigated if seeding HUVECs in a peripheral channel of the device and introducing a concentration gradient of vascular endothelial growth factor (VEGF) would stimulate endothelial network formation directed by a growth factor gradient, similar to angiogenesis in vivo. This was repeated under hypoxic conditions to more accurately mimic the in vivo angiogenic environment, but significant endothelial network formation was not observed and seeding of HUVECs in the peripheral channel presented no perceptible improvements. The final set of experiments investigated if returning HUVECs to the center chamber in local co-culture with HDFs and exposing devices to hypoxic conditions would provide the necessary angiogenic environment to stimulate endothelial network formation within the microfluidic device. Lack of quantifiable endothelial network formation in the final set of experiments led to an analysis of 3D HUVEC colony formation, however, no statistically significant trends were discovered. Even though no significant differences were found, these experiments succeeded in developing a protocol for plating human cells in the novel microfluidic device that can be translated to the tumor side of the Microphysiological Systems lab. From these experiments we can also conclude that co-cultures of HUVECs and HDFs can survive and form into colonies within the novel microfluidic device but additional angiogenic stimuli are necessary to develop robust endothelial networks. Based on the current literature and knowledge gained throughout the experiments presented here, several suggestions are presented to potentially stimulate angiogenesis and develop endothelial networks in the device such as increasing cell densities, varying length of incubation, introducing mediators of angiogenesis like nitric oxide, and addition of tumor cells.
533 $a Electronic reproduction. $b Ann Arbor, Mich. : $c ProQuest, $d 2024
538 $a Mode of access: World Wide Web
650 4 $a Cellular biology. $3 1148666
650 4 $a Microbiology. $3 591510
653 $a Tumor cells
653 $a Nitric oxide
653 $a Human dermal fibroblasts
653 $a Vascularized tumor model
653 $a Angiogenic environment
655 7 $a Electronic books. $2 local $3 554714
690 $a 0379
690 $a 0410
710 2 $a California Polytechnic State University. $3 1437733
710 2 $a ProQuest Information and Learning Co. $3 1178819
773 0 $t Masters Abstracts International $g 85-06.
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30973856 $z click for full text (PQDT)