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Scientists 1: Animal Rights Extremists 0

04.08.2008
A new proof on why mice and other mammals are good experimental models to understand human biology

The architecture of haematopoiesis – which is the process by which all blood cells originate – is essentially the same throughout the mammal world, report scientists in the Proceedings of the Royal Society.

This is an unexpected result considering the thousands of mammals’ species with a myriad of habitats and lifestyles, as so well demonstrated when comparing the 30 mm flying bumblebee bat and the 30 metre-long aquatic blue whale both mammals.

But the work now published shows that the variations in the blood system - necessary to adapt to the evolutionary changes found within the mammals’ world -can be explained quantitatively (for example by producing more cells or having the cells dividing faster), and are directly correlated to the animals’ body mass and do not require any fundamental alteration in the haematopoietic process. This unified view of haematopoiesis - where both its architecture and function is maintained throughout a group as important as the mammals - have many and important implications.

For a start it gives support to the view that mice and other small mammals are good experimental models to understand humans’ physiology as well as to develop new treatments to human diseases. And used directly in humans these results can help improve things as diverse as bone marrow transplants or leukaemia’s treatments just to mention a few examples

The amazing complexity of the biological world can be explained (and predicted) mathematically and formulas that relate different biological functions, anticipating how a system will perform, are major tools to understand living organisms. One such example is allometric scaling a mathematical technique that describes the relationships between the rate of some biological variables (for example the number of cell divisions per time) and the organism’s body mass. In biology size is crucial as all body functions are related to the animal’s metabolism, and this is linked to its body mass. So, in fact, many biological variables can be directly correlated to mass. Allometric scaling formulas describe these relationships and are used to understand and even predict the behaviour of the body.

And a phenomenon that recently has been linked to mass via allometric models is haematopoiesis - the process by which all blood cells are formed, from platelets (crucial to blood coagulation) to white blood cells (the basis of the immune response) and red blood cells ( responsible for carrying oxygen throughout the body to all cells).

Scientists know that the haematopoietic process is organised as a tree where hematopoietic stem cells (HSC) - which have the ability to differentiate into all the different blood cells - represent the trunk from which a multitude of branches comes out, each dividing again and again, until in the end a type of blood cell is generated. It is also known that HSC are divided into two groups, quiescent HSC - which serve as a reserve pool - and active HSC - those that divide and differentiate into the many blood cells. Although the basis of the whole process is relatively well known, the possible differences between very different animals - for example humans and insects or even the bumblebee bat and the blue whale - are much less clear

And, as HSC are the root of the whole haematopoietic process, to understand better their behaviour in different animals has been seen as a way to get closer to the real nature of haematopoiesis changes throughout the different animals.

And in fact, recent research is beginning to give us some clues on what can be going on. For a start, through mathematical reasoning it has been shown in several mammals how HSC proliferation is related to the animal’s body mass, with these cells dividing faster in smaller organisms. These results, obtained by mathematical deduction, were supported by experimental work (so done in a laboratory) in non-human primates that revealed that the smaller the primates, the faster was their HSC proliferation.

Finally it was also shown that active HSC from different organisms when grown in laboratory– so out of the body– divided at very similar rates, a result strikingly different from what was seen when their division was measured inside the animal. This last result further supported the idea that the organisms’ metabolism affected HSC division explaining the different division rates found in different sized animals.

All these observations led David Dingli, a haematologist from the Mayo Clinic in Minnesota USA, together with two theoretical physicists, Arne Traulsen and Jorge M. Pacheco respectively from the Mayo Clinic in Minnesota USA, the Max Planck Institute for Evolutionary Biology in Germany and the Department of Physics at Lisbon University in Portugal, to decide to use allometric tools to understand HSC behaviour and the possible haematopoiesis changes throughout mammal’s evolution.

Their first results predicted that HSC replicate faster in a mouse than in a cat than in a human and they were even able to calculate the approximate HSC divisions’ rate in each of these species. Both results were supported by experimental data from other researchers, showing the validity of the allometric scaling approach used by Dingli, Traulsen and Pacheco.

Their second prediction involved the number of divisions that any given HSC goes during its life time, which they concluded was constant among mammals, something that has been proposed before but never proved. Dingli, Traulsen and Pacheco, however, could explain this allometrically since, even if smaller animals have faster HSC divisions, bigger animals with slower HSC rates compensate this by having a longer life expectancy.

To further confirm their model the researchers calculated the daily bone marrow production of HSC in several mammals to find that the number of cells found by them were compatible with those obtained by directly working in animals, with the number of cells produced by a mouse during its lifetime (around 2 years) similar to the ones produced by humans in one day, and cats in a week. These results supported the validity of the scientists’ first two findings and their model. It also revealed how the haematopoietic demands of different animals is so very different.

Dingli, Traulsen and Pacheco’s results, together with experimental data by others, strongly support the idea of a common hematopoietic process, at least among mammals, despite the changes that appeared throughout evolution within this group. Adaptation to the different needs of different mammals is simply a question of quantity - different HSC numbers or division rates - directly related to the animal’s body mass and without affecting the basic architecture and functions of the haematopoietic process. In this way smaller animals, like mice, as they need less active HSC differentiating, may simply have a bigger HSC quiescent compartment After all, the main principle of evolutionary biology is “maintain what is effective, adapting in simple ways to higher complexities when necessary”.

Dingli, Traulsen and Pacheco’s work clearly shows how mathematical modelling – so many time ignored by pure biologists - can help understand complex biological systems. The model here described can now, for example, help to predict the minimum number of cells necessary for an optimum bone marrow transplant, or bone marrow dynamics both in health or disease or even how to better extrapolate to humans, experimental results found when studying HSC in animal models.

And it is, no doubt, an important support for the validity of using of animal models to understand the biology of humans, contrary to the opinion of so many animal rights groups. Catarania Amorim

This article can be republished without charge provided Catarina Amorim is acknowledged as the source at the top or the bottom of the story. If you use the full piece please add: Piece by Catarina Amorim (catarina.amorim at linacre.ox.ac.uk)

Contacts for the authors of the original paper
Jorge M. Pacheco - pacheco@cii.fc.ul.pt
tel: +351 21 790 4891
fax: +351 21 795 4288
David Dingli - dingli.david@mayo.edu

Catarina Amorim | alfa
Further information:
http://journals.royalsociety.org/content/w253174843634560/

Further reports about: Biology Dingli HSC Pacheco Traulsen allometric haematopoiesis haematopoietic marrow

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