Space Biology As Of Today

SPACE HABITATION

We live 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....

In search 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.

SPACE BIOTECHNOLOGY

Freedom 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.

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 is possible using microgravity.

TISSUES GROWN UNDER MICROGRAVITY

A continuing 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.

1. Miniliver By New Castle University

Photo courtesy BBC news article - Liver cells grown from cord blood

According 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.

2. Cartilage

 Between 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.

3. Heart tissue

 Freed's 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

EFFECTS OF MICROGRAVITY ON THE CARDIOVASCULAR SYSTEM

 The 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.

Research programs at Vascular Biology Lab

AU-KBC Research Centre

GROWING BLOOD VESSELS OUTSIDE THE BODY

The 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 (8).

Clinical importance and challenges of grafting blood vessels

 Vascular 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).

Microgravity as a bioreactor for growing blood vessel: Is it a theory or real?

Microgravity 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.

Modulating 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.

Our mission

We are 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.

References

Prominent Space Research Establishments

National Aeronautics and Space Administration

http://www.nasa.gov/home/

Indian Space Research Organisation

http://www.isro.org/

European space agency

http://www.esa.int/esaSC/index.html

Japan Aerospace Exploration Agency

http://www.jaxa.jp/index_e.html

Space Research institute ( Russia)

www.iki.rssi.ru/eng

Canadian space agency

http://www.space.gc.ca/asc/eng/default.asp

British National Space Centre

http://www.bnsc.gov.uk/home.aspx?nid=3191

South African Space Portal

http://www.space.gov.za/

Laboratories working in the field of Space Biology

The Space Biology Group of the Swiss Federal Institute of Technology, ETH Zürich

http://www.spacebiol.ethz.ch/research/index

M. Hughes-Fulford lab

http://www.spacedu.com/

Dr. Gordana Vunjak-Novakovic lab

http://stuff.mit.edu/people/gordana/

Dr. Lisa E. Freed

http://stuff.mit.edu/people/lfreed/

Dr. A Sundaresan

http://nasa.gov/