Biology As Of Today
in an era where efforts are being made to make space accessible
to as many people as possible, with earth becoming more and more
crowded, more suffocating....
of new space, people will go beyond earth and may eventually find
space more favourable for habitation. For that to happen, scientists
have to understand how the human body will react to these new experiences.
Studying problems that occur in microgravity can help researchers
better understand similar problems on Earth under gravity as well.
Hence, finding solutions for space flight-related problems can help
people suffering from related maladies on Earth.
from gravitational force offers a favorable environment for cell
and tissue culture mimicking natural growth and easier self-association
of cells unlike traditional cultures . Microgravity can yield three-dimensional
tissue specimens that can serve as conduits for growth and development
of biological transplants.
production of recombinant proteins or physiologically active substances
and culture animal cells to form high density 3-D structure model
for studying the complex order of tissue in a culture system that
can be manipulated by drugs, hormones, and genetic engineering is
possible using microgravity.
program of research and development focuses on engineering of functional
cartilage and cardiac muscle for scientific research and for eventual
use in transplants. The program involves the use of cells, polymer
scaffolds, and bioreactor vessels. A polymer scaffold serves as
a three-dimensional structure to which cells can attach. Once attached,
the cells can regenerate full tissues, and then the polymer scaffold
becomes biodegraded when no longer needed. A bioreactor provides
an appropriate environment and physiological signals during the
development of tissues.
By New Castle University
Photo courtesy BBC
news article - Liver cells grown from cord blood
to the BBC news sections liver were created using stem cells from
umbilical cords by a team at Newcastle University. It is hoped the
"mini-livers" will be used to test drugs, avoiding incidents
like the North wick Park trial in which six patients became seriously
ill. The tissue is grown using a microgravity bioreactor, a piece
of equipment derived from NASA technology, which aids the creation
of cells by mimicking weightlessness.
September 1996 and January 1997, Freed and Vunjak-Novakovic with
NASA colleagues grew cartilage aboard the Space Station Mir in the
first tissue-engineering experiment in space. They published their
results in the December 1997 issue of the Proceedings of the
National Academy of Sciences.
first successful experiment
in engineering heart tissue: the cells she had "seeded"
on a three-dimensional scaffold outside a living body began beating
as one. "It was my most awesome laboratory moment ever. No
one had ever done this before," said Freed
OF MICROGRAVITY ON THE CARDIOVASCULAR SYSTEM
condition of microgravity during spaceflight imposes a new challenge
to the cardiovascular system and to its homeostatic mechanisms.
Cardiovascular system is perturbed during space travel as indicated
by altered cardiac input and output. Indirect evidences that endothelial
dysfunction is implicated in many anomalies of cardiovascular system
arising during long duration space flights. The migration, proliferation
and cell signaling of endothelial cells in response to stimulus
and factors play an important role in modulating the endothelium
and have far reaching effects on cardiovascular system. Level of
cGMP, an important biochemical endothelial marker; has been shown
to decrease considerably after space travel in astronaut blood plasma.
programs at Vascular Biology Lab
AU-KBC Research Centre
the basic functions of endothelial cells - Nitric oxide production,
wound healing, migration and proliferation in microgravity.
- Probing the microgravity-induced
changes in cells own behavior and communication with its neighbors
in the absence of gravity.
- Using microgravity as bioreactor to
grow blood vessels in bio-scaffolds
BLOOD VESSELS OUTSIDE THE BODY
idea of using technology to grow collateral blood vessel is an useful
alternative for myocardial ischemia and other spectrum of angiogenesis
disorders refractory to conventional treatments. Discovery of FGF
(fibroblast growth factor)(1, 2), as an endothelial mitogen by Gospodarowicz
and colleagues laid the foundation for the pursuit of more angiogenesis
inducing agents as acidic FGF (aFGF or FGF-1) in a dog ischemic
heart model (3) and VEGF A capable of inducing collateral growth
in rabbit (4), mouse (5) and canine heart (6). This was followed
by gene therapy approach using naked plasmid DNA encoding for a
secreted protein which exerted a therapeutic effect, improving tissue
perfusion and alleviating ischemia (7) Later on application of bone
marrow derived endothelial progenitor cells in patients with critical
limb ischemia demonstrated evidence for physiologic improvement
importance and challenges of grafting blood vessels
tissue engineering applies the principles of biology and engineering
to the development of functional 3D tissues outside of the body
for restoring, maintaining and improving the functions of damaged
tissue ( 10 ). First clinical experiences have been published using
bioengineered skin, cartilage, and vascular grafts (11-13). Although
vascular bypass grafting remains the mainstay for revascularization
for ischemic heart disease and peripheral vascular disease, many
patients do not have healthy vessels suitable for harvest. Thus,
prosthetic grafts made of synthetic polymers were developed, but
their use is limited to high-flow/low-resistance conditions because
of poor elasticity, low compliance, and thrombogenicity of their
synthetic surfaces. To circumvent these problems several laboratories
have produced in vivo or in vitro tissue-engineered blood vessels
using molds or prosthetic or biodegradable scaffolds. Recently,
conduits are being used to ensure there is no rejection. Once remodeling
occurs after grafting, the tissue is almost indistinguishable from
native vessels. This conduit derived from cells of bone marrow origin,
opens up new possibilities in vascular modeling and remodeling (14).
as a bioreactor for growing blood vessel: Is it a theory or real?
can yield three-dimensional tissue specimens that can serve as conduits
for growth and development of biological transplants. Microgravity
as a force is being used for large-scale production of recombinant
proteins or physiologically active substances and culture animal
cells to form high-density 3-D structure model for studying the
complex order of tissue in a culture system that can be manipulated
by drugs, hormones, and genetic engineering. A number of tissues
have been grown in microgravity. Freed and Vunjak-Novakovic with
NASA grew cartilage aboard the Space Station Mir in the first tissue-engineering
experiment in space (15-16). Another report described generation
of coherently beating aggregates from neonatal rat heart cells by
exposing cell suspensions with fibronectin coated polystyrene microcarrier
beads or oriented collagen fibers to microgravity in bioreactor
cultures (17). Newcastle university team used stem cells from umbilical
cords to create sections of liver in a microgravity bioreactor.
According to a recent review, more than 25 different cell types
has been flown to space to understand the cell biology under microgravity
environment, which demonstrates that cytoskeleton acts like a sensor
and signals phosphorylation of down stream signaling molecules to
adjust them to the new climate of low gravity (18). Understanding
the microgravity driven formation of tissue will be a step forward
in space biotechnology.
endothelial cells to grow and differentiate into blood vessels requires
numerous factors and stimulation that cannot be provided in conventional
cell culture systems. Development of microgravity bioreactors has
revolutionized biotechnology proving to be a better culture system,
providing important physiological cues for cell aggregation and
cell growth. A number of tissues grown under microgravity like heart,
cartilage, mini liver testify the feasibility of using microgravity
for growing transplantable tissue in vitro.
aiming to grow blood conduits from endothelial cells under microgravity.
Results of our recent experiments demonstrate that microgravity
promotes endothelial migration, tube formation and nitric oxide
production followed by faster formation of endothelial conduits
in three dimensional matrigel blocks. In ovo microgravity experiments
using fertilized chick embryo further furnished support to the concept
that microgravity enhanced the rate of blood vessel formation. Further
studies aiming at the dissection of the mechanism of the formation
of microgravity based blood conduits prove that an induction and
activation of NOS facilitates the growth of conduits. Our next target
is to check the suitability of the microgravity engineered blood
conduits as transplantable template to grow blood vessels in focal
areas of cardiac infarct in animal models.
- Höckel M, Burke FJ. Angiotropin treatment prevents
flap necrosis and enhances dermal regeneration in rabbits. Arch.
- Salvage of infarcted myocardium by angiogenic action
of basic fibroblast growth factor Yanagisawa-miwa, A. et al.
Science 257, 1401-1403 (1992)
- Effects of acidic fibroblast growth factor on normal
and ischemic myocardium Banai, S. et al.Circ. Res. 69, 76-85
- Takeshita S, Zheng LP, Brogi E, Kearney M, Pu L-Q,
Bunting S, Ferrara N, Symes JF, Isner JM. Therapeutic angiogenesis.
A single intraarterial bolus of vascular endothelial growth
factor augments revascularization in a rabbit ischemic hind
limb model. J. Clin. Invest. 1994;93:662- 670.
- Couffinhal T, Silver M, Zheng LP, Kearney M, Witzenbichler
B, Isner JM. Mouse model of angiogenesis. Am. J. Pathol. 1998;152:1667-1679.
- Banai S, Jaklitsch MT, Shou M, Lazarous DF, Scheinowitz
M, Biro S, Epstein SE, Unger EF. Angiogenic-induced enhancement
of collateral blood flow to ischemic myocardium by vascular
endothelial growth factor in dogs. Circulation. 1994; 89:2183-2189.
- Tsurumi, Y. et al Direct intramuscular gene transfer
of naked DNA encoding vascular endothelial growth factor augments
collateral development and tissue perfusion . Circulation 94,
- Takahashi, T. et al.Ischemia- and cytokine-induced
mobilization of bone marrow-derived endothelial progenitor cells
for neovascularization Nat. Med. 5, 434-438 (1999)
- J. Folkman and Y. Shing, J. Biol. Chem. 267, 10931
(1992); W. Schaper, M. D. Brahander, P. Lewi, Circ. Res. 28,
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- Langer, R. & Vacanti, J. P. Tissue engineering
(1993) Science 260, 920–926.
- Garfein ES, Orgill DP, Pribaz JJ. Clinical applications
of tissue engineered constructs. Clin Plast Surg. 2003;30:485–
- Shinoka T, Matsumura K, Hibino N, Naito Y, Murata
A, Kosaka Y,Kurosawa H. [Clinical practice of transplantation
of regenerated blood vessels using bone marrow cells]. Nippon
Naika Gakkai Zasshi. 2003; 92:1776 –1780.
- Rahaman MN , Mao JJ Stem cell-based composite tissue
constructs for regenerative medicine. Biotechnol Bioeng. 2005.
- Tissue-Engineered Blood Vessels: Alternative to Autologous
Grafts? Michel R. Hoenig, Gordon R. Campbell, Barbara E. Rolfe,
and Julie H. Campbell Arterioscler. Thromb. Vasc. Biol., Jun
2005; 25: 1128 - 1134.
- Lisa E. Freed, Robert Langer, Ivan Martin, Neal R.
Pellis, and Gordana Vunjak-Novakovic Tissue engineering of cartilage
in space . PNAS 1997;94;13885-13890
- Ming Pei , Luis A. Solchaga, Joachim Seidel, Li Zeng,
Gordana Vunjak-Novakovic, Arnold I. Caplan, and Lisa E. Freed.
Bioreactors mediate the effectiveness of tissue engineering
scaffold .FASEB J, Aug 2002
- Cardiac muscle tissue engineering: toward an in vitro
model for electrophysiological studies." American Journal
of Physiology, Heart and Circulatory Physiology. Vol. 277, Issue
2, H433-H444, August 1999. N. Bursac, M. Papadaki, R. J. Cohen,
F. J. Schoen, S. R. Eisenberg, R. Carrier, G. Vunjak-Novakovic,
and L. E. Freed
- Donald Ingber How cells (might) sense microgravity
The FASEB Journal. 1999;13:S3-S15.)
Space Research Establishments
and Space Administration
Indian Space Research
European space agency
Japan Aerospace Exploration
Space Research institute
Canadian space agency
South African Space
working in the field of Space Biology
The Space Biology
Group of the Swiss Federal Institute of Technology, ETH Zürich
Dr. Gordana Vunjak-Novakovic
Dr. Lisa E. Freed
Dr. A Sundaresan