by Jalees Rehman
Back in 2001, when we first began studying how regenerative cells (stem cells or more mature progenitor cells) enhance blood vessel growth, our group as well as many of our colleagues focused on one specific type of blood vessel: arteries. Arteries are responsible for supplying oxygen to all organs and tissues of the body and arteries are more likely to develop gradual plaque build-up (atherosclerosis) than veins or networks of smaller blood vessels (capillaries). Once the amount of plaque in an artery reaches a critical threshold, the oxygenation of the supplied tissues and organs becomes compromised. In addition to this build-up of plaque and gradual decline of organ function, arterial plaques can rupture and cause severe sudden damage such as a heart attack. The conventional approach to treating arterial blockages in the heart was to either perform an open-heart bypass surgery in which blocked arteries were manually bypassed or to place a tube-like “stent” in the blocked artery to restore the oxygen supply. The hope was that injections of regenerative cells would ultimately replace the invasive procedures because the stem cells would convert into blood vessel cells, form healthy new arteries and naturally bypass the blockages in the existing arteries.
As is often the case in biomedical research, this initial approach turned out to be fraught with difficulties. The early animal studies were quite promising and the injected cells appeared to stimulate the growth of blood vessels, but the first clinical trials were less successful. It was very difficult to retain the injected cells in the desired arteries or tissues, and even harder to track the fate of the cells. Which stem cells should be injected? Where should they be injected? How many? Can one obtain enough stem cells from an individual patient so that one could use his or her own cells for the cell therapy? How does one guide the injected cells to the correct location, and then guide the cells to form functional blood vessel structures? Would the stem cells of a patient with chronic diseases such as diabetes or high blood pressure be suitable for therapies, or would such a patient have to rely on stem cells from healthier individuals and thus risk the complication of immune rejection?