The frontier of wound care - stem-cell research in the UAE

Shortly after their usual period of ovulation, the female hamsters – aged eight to 12 weeks, of the Syrian ‘golden’ variety – were injected with 20 units of pregnant mare serum. Three and a half days later, the now hyper-fertile horde was placed overnight in an enclosure with three males. After a series of events that require no elaboration, blastocysts – the mid-stage between a fertilised egg and an embryo – were flushed from the uteruses of the female hamsters. These were then placed in a specially treated culture dish and, after a couple of days, attached to feeder cells.

Little could these furry test subjects know the duty they had performed to science. Over time, the blastocysts would mutate into colonies of embryonic stem cells. The innovation was one in a long line of successful experiments with the building block of cellular development; seven years later, scientists would accomplish something similar with primates. By 2014, it was not only possible to isolate human embryonic stem cells, but independently produce them from adult cells through therapeutic cloning.

Controversial therapy

The potential uses for stem-cell therapy are vast. By injecting a batch of stem cells close to a wound or an organ where their natural production has proved deficient, the theory is that the body of the patient will use them as raw materials to rebuild the stricken area. This is, however, a simplified version of events. It does not take into regard the ethical qualms many researchers have encountered among hospital ethics boards and even governments – a key point of contention worldwide in the use of embryonic stem cells has been the judgment as to whether it technically constitutes human experimentation – as well as the hard and complicated science of spurring meaningful regeneration of damaged cellular structures through their use.

Despite this, there have been notable breakthroughs in recent years. In 2015, Chiesi’s Holoclar treatment was approved for use in Europe as the first stem-cell therapy, dedicated to the treatment of limbal stem-cell deficiency, a condition that can result in chronic pain and blindness. Bone marrow transplants, using the mesenchymal stem cells (MSCs) that can be stimulated into dedicated bone, muscle or cartilage cells, are now also a common treatment for leukaemia. The potential for MSCs in wound care has also been amply demonstrated through animal testing, and it is into this field of study that a group of doctors, led by Dr Saqer al-Mualla and his colleagues at Al Qassimi Hospital in Sharjah, UAE, have recently embarked. The result is the development of a technique focused on treating chronic wounds with a targeted application of stem cells derived from adipose tissue.

Growing interest

Al-Mualla is, strictly speaking, a plastic surgeon, having completed his doctorate in the field in the early 2000s after receiving his MD in Gothenburg, Sweden. Since then, he has steadily risen through the ranks at Al Qassimi Hospital, eventually becoming head of its plastic surgery department and deputy CEO.

“At the time, when I went into plastic surgery, it wasn’t a field that was well-developed in the UAE,” al-Mualla reflects. “It’s a challenging thing. Some practitioners will be looking to go into cosmetic surgery, or [want] a challenge, and it was the latter aspect that made me think, ‘Oh, I can innovate more in this field because it’s still fairly primitive.’ That was back in the 90s, and now, it’s a well-developed sector.”

As a subset of plastic surgery, wound care was particularly interesting to al-Mualla. It carried its own set of challenges, not least in that it was also a sector that suffered from a dearth of region-specific research and investment. “We started a wound-care society in the beginning of 2005, but it was stopped cold,” the doctor recalls. “There wasn’t much interest in it.”

Of course, matters have since changed in the UAE. Chronic wound care in particular is a field of medicine that places a significant financial burden on the country’s health system. From diagnosis to the placement of a dressing, followed by its repeated replacement over an extended period of time, it is a cost that hospitals like Al Qassimi can do without, especially while health systems across the Gulf confront new medical battles in the form of superbug proliferation and diabetic foot care.

It was from this base that al-Mualla and his colleagues began a sustained round of research into enhancing wound care for patients, from which the hospital’s new stem-cell therapy sprang. On paper, the technique is straightforward: samples of abdominal fat are removed from the patient via liposuction, which are then sent to laboratories in Dubai run by Cytori Therapies, a bioresearch company. After a week, batches of stem cells mixed with collagen are returned to Al Qassimi Hospital. These are then applied to the wound to accelerate the healing process.

Although its direct inspiration was a procedure developed in Italy in the mid-2000s, wherein stem cells were injected into the face for cosmetic purposes, the technique developed at Al Qassimi Hospital follows on from several key studies in Europe and Asia that have demonstrated the value of using stem cells to spur wound closure and skin regeneration. It is only now, however, that stem-cell research has begun to flower in the UAE. Promising developments are seemingly announced every month. From experimentation with autologous mononuclear stem cells in the treatment of degenerative disease at Burjeel Hospital in Abu Dhabi, to therapies for hereditary retinal conditions being developed at Al-Zahra Hospital in Dubai, al-Mualla’s work forms part of a growing corpus of research that promises to push our understanding of the potential of stem cells ever outward.

Early days

Of course, exploring new frontiers has its own challenges. While al-Mualla has experienced several successes in deploying the new technique – earlier this summer, two patients in their 20s admitted with chronic wounds deriving from paralysis and diabetes responded well to the treatment – the study has not exactly been free of difficulties. Firstly, the extraction of the necessary tissue sample from patients can sometimes prove challenging.

“One of our first cases involved a patient with multiple scars in the abdomen,” al-Mualla recalls. “When you see that type of scar, you have to ask yourself where you should take the fat from.” While that sample was eventually collected, it did remind the plastic surgeon that not all medical practitioners would prove as well versed in liposuction as he. Al-Mualla acknowledges that, if the technique were eventually to be approved for widespread use, a small amount of extra training might be required.

Additionally, not all cases seem to merit the new therapy. Al-Mualla encountered some cases during the study where the technique was either difficult to implement or did not yield significant results. In his mind, it’s proof that a clearer set of criteria are needed for when it is appropriate to treat chronic wounds with stem cells. The treatment itself is, after all, extremely expensive. “We need to conduct a broader study on this technique because, to be very frank, it’s not that convincing a treatment if you’re not selective in the cases where you apply it and don’t lay down proper guidelines,” al-Mualla explains.

Of course, Al Qassimi’s venturing into stem-cell therapy is not the only arrow in its quiver when it comes to research into wound care. Classification is one area that has benefitted in recent years, with the introduction of the ‘e-Kare’ iPad app to hospitals across the UAE. The application is a quick and easy way for doctors to quickly determine the size and depth of wounds presented to them by patients, remotely if necessary. It has proved to be an incredible time saver when it comes to differentiating between which wounds merit hospital treatment and which can be treated at home or in smaller medical centres.

“You see all the pictures, and it shows you if there has been an improvement or not,” says al-Mualla. “Accordingly, you can see whether the dressing has been right or wrong, and if you need to conduct a surgical procedure. Plus, this is good for the patient: he doesn’t need to come to a hospital. He can be treated in his home or somewhere close by.”

Then, of course, there is the doctor’s foray into natural extracellular matrices. Experimenting with a bacterial cellulose formulation called Nanoskin, al-Mualla collaborated with Brazilian academics to test its ability to perform “the tasks necessary for tissue formation, maintenance, regulation and function”, to quote the team’s recently published article in the Journal of Biomaterials and Nanobiotechnology. Besides finding that the application of Nanoskin did decrease recovery time and treatment costs, al-Mualla is also convinced that this avenue of wound-care research may in fact be more practical to pursue than the stem-cell therapy route.

“With that study, it took us almost a year to get approval,” he recalls.

Despite this, Al-Mualla’s progress has been considerable. Although the stem-cell study is in the process of being written, the doctors’ efforts have served to deepen an understanding of practical wound care among the medical community in the UAE, which was, of course, his ultimate goal. “What’s lacking here in the Middle East is research,” says al-Mualla. “There aren’t many published studies or articles on many things here, so if you don’t write it, it doesn’t exist. We need to emphasise the value of research. That mentality is coming, and hopefully, things will move very fast.”