Saving legs through stem cell transplantation

An ongoing trial uses adult stem cells from bone marrow to grow collateral blood vessels

The clinical trial, which started in December last year, would enrol 60 volunteers

Trials done in a few countries have shown encouraging results

Smoking does not affect the lungs alone. The nicotine present in the blood has a destructive effect on blood vessel muscles. It causes the muscles to constrict and damages the vessel’s inner lining. The end result is that the main arteries that supply blood get blocked.

While nicotine affects all the vessels (arteries), the worst affected parts are those below the knee joint. “Elsewhere there are rich collaterals [smaller vessels that branch off from the main arteries] and [the organs] do not depend on one artery for blood and the requirement of blood is far more in the legs,” explained Prof. K.S. Vijayaragavan, Head of the Department of Vascular Surgery, Sri Ramachandra University near Chennai.

Blood requirement by the legs goes up 12 times depending on the kind of exercise the person is engaged.

The disease turns the vessels into rigid tubes, thus making them incapable of expanding. And with the vessel muscles constricted, the flow of blood to the peripheral parts gets compromised. The human system reads this as lack of RBCs and produces more of them.

With more RBCs, the blood becomes thicker and this compounds the problem as thicker blood has to flow through narrower vessels.

Unlike in the case of blocks typical of atherosclerosis caused by cholesterol, the blocks seen in legs and caused by nicotine (thrombo angitis obliterance) start from the toe and move up towards the thigh.

Early warning

Since the only symptoms are pain and inability to walk long distances, patients generally ignore the early warnings and turn up when the disease is at an advanced state. The only solution is amputation.

Though exact figures are not available, the prevalence of the disease in India is high, according to Prof. Vijayaragavan.

While performing a bypass surgery or doing a angioplasty are recommended when detected early, growing more co-laterals is the only recourse to save the legs from amputation when the disease is at an advanced stage.

A clinical trial is currently under way at Shri Ramachandra University to grow such collaterals using adult stem cells collected from the bone marrow of the same patient. The study, which started in December last year, would enrol 60 volunteers.

The Chennai based Asia Cryo-Cell Private Ltd, a private cord blood bank, is an equity partner at TRICell Stem Cell Centre, which is based at the University, where the trial is being conducted.
Two groups

Of the 60 volunteers, the first group of 30 would get 40 injections of stem cell concentrate very close to the blood vessels and the second group of 30 volunteers would get 20 injections very close to the blood vessels and another 20 injections into the main artery above the block.
Criterion used

“At least one of the three arteries should allow blood to at least trickle; else it is useless,” said Prof. Vijayaragavan, Principal Investigator of the trial explaining the criterion used for selecting the volunteers for the second group.

The injections — bone marrow aspirate — contain not just stem cells but also other supporting cells that complement them, such as platelets and RBCs. The stem cells and the supporting cells are separated and concentrated using a small instrument.

Such trials are already under way at a few centres in the U.S. “The same protocol followed in the U.S. is followed here,” he said. Many trials done in a few countries have shown encouraging results.
Safe and effective

One of the first studies reported in the journal Lancet in 2002 found autologous implantation of bone marrow cells to be safe and effective for achieving therapeutic vessel formation. The results were based on a randomised controlled pilot study.

The authors found a “…striking increase in number of visible collaterals vessels in 27 of 45 patients.” They also reported that “… bone-marrow transplantation effectively increased blood flow in all 45 legs.”