
AsianScientist (Jun. 9, 2014) – As a scientist new to Singapore, what struck me the most about my colleagues at the National University of Singapore (NUS) and National University Health System (NUHS) was their enthusiasm to discuss new ideas, share resources and collaborate. To me, this indicates a scientific culture that has not yet become rigid about science or innovation; a quality very important to me for the advancement of my scientific endeavors.
My official appointment at NUS commenced in mid September 2013. I arrived here from the Swiss Federal Institute of Technology, ETH, where I had been for the last 14 years. At ETH, I founded and headed the Rehabilitation and Regenerative Strategies group in the space biology program; which, I suppose, is the reason why NUHS department of surgery was interested in my work. The European Space Agency was funding my work to develop new technologies and therapeutic strategies to slow muscle and bone loss during manned-space flight, a process commonly referred to as space atrophy.
Feeling the pull of gravity
Why do we lose muscle and bone mass in space? Simply put, we are mechanosensitive beings. This means that the majority of our body’s tissues arise from developmental programs regulated by mechanical input. One of the most important developmental mechanical forces we encounter in everyday life is the unyielding force of gravity. Every moment of our waking existence, we are combating the force of gravity to one degree or other, depending on whether we are in lying in bed, siting at our desk, walking to a meeting or climbing stairs. Most of us take this fundamental fact for granted. Simply imagine what would happen if we allowed ourselves to succumb to the force of gravity? We would end up flat on the floor, truly feeling our weights for the first time. Indeed, most of our daily caloric expenditure is dedicated to combating the force of gravity in order to remain standing or seated.
But why do we use mechanical forces to determine our tissue mass? This is because we are always subject to gravity – the most fundamental of all mechanical forces – and yet need to move around it in as efficiently as possible for our survival. If we had insufficient muscle mass we would find it difficult to move around and fend for ourselves, we would be too weak. If, on the other hand, we were too big and bulky we would need to carry a lot of extra weight around, which would be a waste of energy. The changes in tissue mass in response to environmental needs is a clear example of biologic optimization.
Interestingly, athletes unwittingly take advantage of this developmental program to increase their muscle and bone mass. When an athlete trains, what he or she is actually doing is increasing the mechanical demand on the body, fooling the body into thinking the mechanical world has changed for good. In response, the body loyally complies and does what is natural to it: increasing its bone density and muscle mass to match the new mechanical environment. Unfortunately, the opposite scenario is also true. Once the mechanical environment returns to what it was, we lose the muscle mass and bone density gained and revert to normal. This is the detraining we experience once we stop exercising. Sadly, inactivity causes us to lose muscle and bone at a faster rate than our gain in response to exercise. Very unfair, indeed.
From space to the ICU
Herein lies the caveat that brought me to NUHS. As I stressed earlier, mechanical forces promote tissue maintenance. However, wound healing often requires the body to be immobilized to allow the damaged tissues to mend. Ironically, this actually serves to undermine the full regenerative capacity of a tissue by short-circuiting its ability to perceive and respond to mechanical forces that it would normally use to instigate regeneration. This is the paradox we face in the clinics.
Another equally counter-productive dimension to this scenario is that the lack of muscle mass in turns slows recovery. Muscle is our largest tissue and has evolved to serve as a reservoir and producer of many of the body’s most important regenerative factors. Importantly, many of these essential repair factors are released by muscle in response to movement. Immobilizing a body part, or an entire individual for that matter, limits the production and release of these regenerative factors, actually slowing recovery.
So, how do you help someone in the intensive care unit (ICU) exercise? You simply cannot and, obviously, you would not want to. Consequently, patients in the ICU lose muscle mass and undergo metabolic destabilization that literally works against their recovery. What is needed is a way to maintain muscle mass in the clinically immobilized without movement that might disrupt inserted catheters, medical monitoring devices and the like.
We have found that precisely designed pulsing electromagnetic fields are perceived by cells as a mechanical force and have some of the same muscle-generating and metabolic stabilizing attributed to exercise but without any mechanical stress on the cell. These could potentially be applied to immobilized patients and slow their rate of muscle loss, forestall metabolic disturbances, improve their recovery and minimize relapses. Up to now, most of our results have been generated in mice. Here at NUS however, we are scheduled to commence human trials with electromagnetic stimulation in the upcoming year for later translation into various clinical scenarios.
In all my years of research in the field of regeneration, no one has ever shared my vision as much as Professor Lee Chueng Neng, head of the department of surgery at NUHS. Encouraged by his support, I packed up shop in Switzerland and am now working in Singapore. Now, the onus is on myself and my new colleagues here at NUHS to make my vision real. I am very confident we will.
Dr. Alfredo Franco-Obregón is a senior research fellow at the department of surgery, NUHS.
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