Regenerative Medicine for Obliterating Vascular Diseases

Obliterating vascular diseases of the lower limbs are more serious pathology because of their consequences. Anatomically, quantity of the arteries are limited ischemia means poor or full absent of the blood flow and oxygen starvation into the tissues. If the ischemia is not eliminated or compensated the tissue necrosis is coming. Finally, a lower limb amputation can be a necessary thing.

Critical limb ischemia is a condition where the blood circulation in the limbs, in most cases the legs, is decreased so that pain and non healing wounds ensue. Mostly, this is a sequel of arteriosclerosis and/or diabetes.

More frequent reason of the limbs ischemia is obliterating atherosclerosis. Atherosclerotic plaques arising in the artery grow and gradually narrow a lumen of the vessel and finally result in full occlusion of the artery. In that way the chronic ischemia is developing.

When the plaque is exposed by thrombosis the lumen of the artery is occluded very fast that is the most frequent reason of acute ischemia of the leg.

Now you have already known that obliterating vascular disease can result in acute and chronic ischemia of the legs. Acute ischemia has fulminant course as a rule and often came to gangrene very fast. The chronic ischemia is a long existing disease which gradually worsens of the blood flow in the lower limbs for many years. Low course of the disease makes it possible for the leg to compensate of the ischemia by the use of cellular mechanisms without necessity of medicines using. The acute ischemia usually requires emergency operation whereas for the chronic ischemia necessity of the operation appears just in severe cases.

As a rule, treatment of the chronic ischemia is started with application of medicines which can be enough for compensation of the poor blood flow during a long period of life. However, in 20-40 % of cases the ischemia gradually increasing can require of an operative intervention. Refusal from the operative treatment necessarily can result in the high amputation.

Except obliterating atherosclerosis the following diseases can be the reason of the lower limbs ischemia:

1. Obliterating endarteritis
2. Obliterating thrombangiitis (Burger’s disease)
3. Diabetes mellitus (diabetic arteriopathy)
4. Congenital structural anomaly and diseases of arteries
5. Damages of arteries

The symptoms of the lower limbs ischemia:

1. Muscular and foot pain at the time of walking demanding of immediate stopping and disappears in few minutes of rest.
2. Paresthesia and filings of numbness in the region of toes and foot.
3. Falling of toes and foot temperature
4. Cyanotic with red color of foot and crus
5. Protractedly nonhealing wounds and ulcers of toes and foot

Depending on quantity and intensity of the symptoms named above there are four rates of the lower limbs ischemia from easy (I rate) to critical (III B - IV rate).

An objective features of the critical ischemia are following:

1. Intermittent claudication which come in few then 200 m of walking
2. Relief and absence of the arterial pulse on different levels of the leg
3. Lowering ankle blood pressure less then 50 - 30 mmHG
4. Lowering toes blood pressure less then 30 mmHG
5. Ankle-brachial index less 0,9
6. Lowering foot and crus temperature by thermography examination
7. Lowering partial oxygen pressure in the foot tissues less then 30 mmHG
8. Stenosis of arteries more then 70 % and occlusions by Doppler’s ultrasonography

NOTE. If few named above symptoms are presented an “appropriate treatment” is necessary. If the treatment was not performed during nearest 6-12 months there is a very high risk of the lower extremity amputation.

What does “appropriate treatment” meaning include? Selection of a method of treatment is depended on stage of the disease and rate of the ischemia. In the beginning (I-II rates) of disease often just conservative treatment is used and includes administration of medicines improving of the blood flow and hemorheology, and holding the atherosclerotic plaques in stable condition as well. In case of critical ischemia the surgical operation is needed. The aim of surgical procedure consists in correction of the narrowing or occluded artery by use of an angioplasty and removing of thrombus together with atherosclerotic plaque.

In case of presence of a long occlusion of the artery when the method of angioplasty can not be applied the bypass method is usually used.

The main problem of the surgical treatment of the obliterating vascular diseases is an early thrombosis of the bypass and operated arteries. Success of the operative intervention in many cases is depended on diameter of the artery. Operations on arteries with small diameter are complicated by early thrombosis with great likelihood. Therefore, operations performed over the knee more successful compare with operations performed on small caliber arteries. Low velocity of the blood flow in small arteries and unavoidable trauma of the arterial wall at the time of operation as well promote early thrombosis. Repeated operations are usually unsuccessful and often lead to leg amputation.

What an outlet from situation when the conservative treatment is ineffective and surgical intervention is less perspective or impracticable? Recent half-age, few methods of local angiogenesis stimulation was investigated and implemented. Some of them are enough traumatic and some methods are connected with development severe complications. But common negative feature of these methods is a low effectiveness.

Last decade methods of cellular stimulation of the local neoangiogenesis have developed very fast and in number of countries they have received wide spreading.

Scientific investigations from Japan, USA, China, Europe, Russia and our own researches have already confirmed high effectiveness of using the stem cells and different grow factors in treatment of lower limbs ischemia.

In our studies we used only bone marrow autologous (patient’s own) cells. This way is absolutely safe for the patient because there are not any immunological conflicts. Moreover, in contrast to majority of clinical researchers we have used a mononuclear cells fraction of the bone marrow because an associated work of stem cells and other cells contained in the fraction gives better expected result.

How it works?

After the cells were implanted directly into the ischemic tissues they go to terminal parts of still functioning vessels by chemotaxis mechanism and special signals from cells suffering from anoxia.

Part of these cells insert into the terminal arterial branches. By the use of division and proliferation of the stem cells the arteries are becoming longer and new vascular (arterial) mesh is created.

The rest cells participate in process of neoangiogenesis by the use of expression of special proteins which regulate and support the process of the division and proliferation of the stem cells.

Finally, in the region recently was suffered from oxygen starvation the new vessels appear and improve feeding of tissues.

Clinically it is characterized by decreasing of full disappearing of pain. The toes and foot is coming hotter. Long time existing ulcers and wounds usually clear oneself and close up. Improving promoted by the stem cells are saved for 3-5 years period according to our clinical studies. However, by reports different researchers this period is going to be longer but, there are not enough clinical dates to say sure about duration of the remission. Obviously, stability of the clinical improvement is depended on individual characteristic of the patient and stage of the disease and severity of the ischemia before the treatment.

Let your legs be healthy!