Biomimetic Components Aiming to Improve in vitro Cardiac Culture Systems as Building

196 Pages·2013·12.76 MB·English

UC Merced
UC Merced Electronic Theses and Dissertations
Title
Biomimetic Components Aiming to Improve in vitro Cardiac Culture Systems as Building
Blocks to Reshape Failing Hearts
Permalink
https://escholarship.org/uc/item/2r51w8wp
Author
Luna, Jesus Isaac
Publication Date
2013

Peer reviewed|Thesis/dissertation
eScholarship.org Powered by the California Digital Library
University of California
Copyright
Jesus Isaac Luna, 2013
All rights reserved
UNIVERSITY OF CALIFORNIA, MERCED
Graduate Program in Biological Engineering and Small-scale Technologies (BEST), of
the School of Engineering

Biomimetic Components Aiming to Improve in vitro Cardiac Tissue Culture
Systems As Building Blocks to Reshape Failing Hearts
by
Jesus Isaac Luna, B.S.

Dissertation Presented
As a requirement for the degree of

Doctor of Philosophy

Committee Members:
Marcos E. García-Ojeda, PhD - Chair
Jennifer O. Manilay, PhD
Wei-Chun Chin, PhD
2013
i
Dedication:

Dedicated with all my heart to my loved Family; my parents Isidra Carrillo Robles and
Porfirio Luna Carrillo; my brothers Rogelio Manuel, Miguel Angel, and José Luis Luna
Carrillo. My dear friend Llonel Nathaniel Onsurez. And To those who light up my
motivation with their lives and hearts: My grandmothers Emilia Carrillo Robles†, Elidia
Carrillo Rodríguez†; and to my uncles Jesús Carrillo Robles†, and Armando Carrillo
Robles†.

ii
The Dissertation of Jesus Isaac Luna is approved, and it is acceptable in quality and form
for publication on microfilm and electronically:

________________________________________________________________________
Jennifer O. Manilay, PhD.

________________________________________________________________________
Wei-Chun Chin, PhD.

________________________________________________________________________
Marcos E. García-Ojeda, PhD. Chair

University of California, Merced

2012
iii
ACKNOWLEDGEMENTS:
PIs:

Marcos E. García Ojeda, Michelle Khine, Kara E. McCloskey

Mentors:

Alice Rushforth, Jesús Ciriza, Jennifer O. Manilay, Stella Alonzo, Joel Reyna Jr.
Martin A. Franco, Richard Miller

Friends:

Llonel Onsurez, María del Pilar Asta, Javier Pérez Robles, Harshani Peiris

Academic Programs and Funding institutions:

• Emergent Behaviors of Integrated Cellular Systems (EBICS)
• California Institute of Regenerative Medicine (CIRM)
• Center of Integrated Nanomechanical Systems (COINS)
• Minority in Health and Health Disparities International Training Program
(MHIRT)
• Biosensing and Bio-actuation summer Institute (BSBA)
• League of United Latin American Citizens (LULAC)
• Migrant Education Program Region XXIII, San Joaquin County Office of
Education

The text of Chapter 3 on this dissertation is a reprint of the material as it
appears in Tissue Engineering part C. The co-author listed in this
publication directed and supervised research which forms the
basis for Chapter 3 of this dissertation.

iv
Curriculum Vitae


Jesus Isaac Luna, PhD Candidate
[email protected]

Graduate Program in Biological Engineering and Small-scale Technologies || School of Engineering ||
University of California, Merced || 5200 North Lake Rd || Merced, CA 95343

EDUCATION

Ph.D.

Biological Engineering and Small-Scale Technologies-Emphasis in Cardiac Tissue Engineering, School
of Engineering, University of California Merced, Merced, California– August 2013.

B.S.

Biological Sciences-Emphasis in Developmental, cell Biology and Immunology, School of Natural
Science, University of California Merced, Merced, California – May 2008.

A.S.

Engineering and Biological Sciences, San Joaquin Delta College Stockton, CA– May 2006

ACADEMIC POSITIONS

2008-2011:

Teaching Assistant, School of Engineering and School of Natural Sciences, University of California,
Merced

2008-2012:
Graduate Student Researcher-Biological Engineering and Small-Scale Technologies, University of
California, Merced

2006-2008:

Undergraduate Student Researcher, School of Engineering and School of Natural Sciences, University of
California, Merced
v
RESEARCH EXPERIENCE

June 2008 – May 2012:

Doctoral Research: University of California, Merced, Graduate program in Biological Engineering and
Small-Scale Technologies, Merced, California
Advisors: Michelle Khine, Kara E. McCloskey, and Marcos E. Garcia-Ojeda
Project: Doctoral Dissertation research focuses on engineering in vitro culture platforms containing multi-
scale surface topography for the generation of diverse anisotropic cell constructs using cardiac cells
including fetal, neonatal, and cardiomyocytes derived from murine and human embryonic stem cells.
Additionally, investigated the cardiomyogenic effect of enriched and characterized fetal Cardiac
Fibroblasts on embryonic stem cells as well mechanisms of cardiac fibrosis in in vitro culture systems.
Oct 2006 – May 2008

Undergraduate Research: University of California, Merced, School of Engineering and School of
Engineering, Merced, California.
Advisors: Marcos E. Garcia-Ojeda, Michelle Khine and Kara E. McCloskey
Project: Undergraduate research involved multiple projects including engineering lab-on-a-chip-like
devices using pre-stressed polystyrene sheets (Shrinky-dinks®). One of my projects involved adapting
these devices, which included microfluidic channels and other microfabricated features, to study
differentiation of blood stem cells into T-cells. Additionally, I developed another microfabricated device
using an inkjet printer and polystyrene sheets for generating micro-wells that could be used for embryoid
body formation using mESC. I also engineered an alternative cost efficient, tunable, and relatively rapid
method for creating anisotropic patterned multi-scale topography that can be used for the generation of
anisotropicaly and aligned confluent monolayers of neonatal cardiomyocytes as well as cardiomyocytes
derived from human embryonic stem cells.

OTHER RESEARCH TRAINING

July 2011

NSF-NSC Biosensing-Bioactuation Summer Institute (BSBA) 2011. National Taiwan University, Taipei,
Taiwan. Integrates advances in informatics, nanotechnology, and deeper understanding of biological
systems for sensing and dynamic control of engineered systems.

July 2010

NSF-NSC Biosensing-Bioactuation Summer Institute (BSBA) 2010, University of Illinois Urbana-
Champaign, Champaign, Illinois. Integrates advances in informatics, nanotechnology, and deeper
understanding of biological systems for sensing and dynamic control of engineered systems.

June 2008-Aug 2008

Center of Integrated Nanomechanical Systems (COINS), University of California Berkeley, and University
of California Merced, Merced, California.
Advisor: Michelle Khine
Project: Fabrication of aligned microtopography for cardiac cell alignment studies using metal coated pre-
stressed polystyrene sheets.
vi
June 2007-Sep 2007

Minority Health and Health Disparities International Research Training (MHIRT)at University of
California, Irvine, Irvine, CA. and Center of Neurobiology, National University of Mexico (UNAM),
Juriquilla, Queretaro, Mexico.
Advisor: Juan Rafael Riesgo Escovar
Project: Characterization of piragua, a gene participating in the dorsal closure process in drosophila
melanogaster.

May 2007-Dec 2007

Center of Integrated Nanomechanical Systems (COINS) University of California Berkeley and University
of California Merced, Merced, CA.
Advisor: Michelle Khine
Project: Fabrication of micro-wells for embryoid body formation using Pre-stressed polystyrene sheets and
an inkjet printer.

FELLOWSHIPS:

Jan 2011-May 2012

Emergent Behaviors of Integrated Cellular Systems (EBICS) Fellowship training. Biological engineering
training program in collaboration with Georgia Tech, Massachusetts Institute of Technology (MIT), and the
University of Illinois Urbana-Champaign.

PUBLICATIONS

1. Hatano, R, Mercurio K, Luna JI, Glaser DE, Leppert V, McCloskey KE. Endothelial Cells Derived
from Embryonic Stem Cells Respond to Cues from Topographical Surface Patterns. Journal of Biological
Engineering , 2013;7(18):1754-1611.th

2. Luna JI, Ciriza J, Garcia-Ojeda M, Lieu DK, Li RA, Fowlkes CC, Khine M, McCloskey KE. Multi-
scale Biomimetic Topography for the Alignment of Neonatal and Embryonic Stem Cell-derived Heart
Cells. Tissue Engineering Part C: Methods, 2011;17(5):579-88. Received the CoverHighlight

3. Chen C, Pegan J, Luna JI, Xia B, McCloskey K, Chin W, Khine M. Shrinky-Dink Hanging Drops: A
Simple Way to Form and Culture Embryoid Bodies. Journal of Visualized Experiments, 2008;
http://www.jove.com/index/Details.stp?ID=692

4. Chen, C.S., Breslauer, D.N., Luna, J.I., Grimes, A., Chin, W.C., Lee, L.P Microfluidics: 3-D
Polystyrene Chips" DOI: 10.1039/b719029h

vii
ORAL AND POSTER ABSTRACTS/ PARTICIPATION AT CONFERENCE PROCEEDINGS

Dec 15, 2011

Fetal Cardiac Fibroblasts Play a Critical Role in Cardiac Fate from Embryonic Stem Cells. Jesus Isaac
Luna, Jesus Ciriza, Jennifer Manilay, Kara M. McCloskey. TERMIS-NA 2011 Continental Conference.
Houston, Texas. (Oral Presentation)

July 25, 2011

Engineering of in vitro cardiac microenvironments for the generation of functional cardiomyocytes for
tissue engineering applications. National Cheng Kung University, Tainan, Taiwan. (Oral Presentation).

July 15, 2011

Extracellular Matrix Coated Surfaces Using Fetal Cardiac Fibroblasts as Tools for Cardiac Tissue
Engineering. 2011 BSBA summer training, National Taiwan University Taipei, Taiwan

June 19, 2010

Multi-scale Biomimetic Topography for the Alignment of Neonatal and Embryonic Stem Cell-derived
Heart Cells. Jesus Isaac Luna, Jesus Ciriza, Kara E. McCloskey, Marcos Ojeda-Garcia, Deborah K. Lieu,
Ronald A Li, Charless C. Fowlkes, Michelle Khine. XI University of California
Bioengineering Symposium University of California, Davis. Davis, California.

June 20, 2009

Wrinkled microtopography to induce cell alignment and maintain contractibility of cardiac myocytes.
Jesus Isaac Luna, Jesus Ciriza, Marcos E. García-Ojeda, and Michelle Khine. X University of California
Bioengineering Symposium University of California Merced, Merced, California. (Oral Presentation).
Nov 3, 2007

Piragua a New Dorsal Closure Gene in Drosophila melanogaster. Jesus-Isaac Luna, Juan Rafael Riesgo
Escovar Nestor Octavio Nazario Yepiz . Sigma Xi 2007 annual meeting. Orlando, Florida.

TEACHING EXPERIENCE

Fall 2010 Teaching Assistant: Principles of Chemistry (CHEM 002), University of
California, Merced, CA.
Spring 2010 Teaching Assistant: Principles of Chemistry (CHEM 002), University of
California, Merced, Merced, CA
Fall 2008 Teaching Assistant: Introduction to Nanotech and nanoscience (MSE 118)

PROFESSIONAL MEMBERSHIPS

Emergent Behaviors in Integrated Cellular Systems- Graduate student leader Consortium 2011-2012
Tissue Engineering and Regenerative Medicine International Society (TERMIS) 2011-present
Biomedical Engineering Society (BMES) 2011-present
American Heart Association 2010-present
Sigma Xi Research Society 2008-present

viii