Endothelial Stem Cell Research
A 12month study called TOPCARE-AMI used bone-marrow derived endothelial stem cells which were cultured in the laboratory and then infused into patients’ blood in the immediate aftermath of a heart attack (Assmus, et al, 2002). The twenty patients in the study group displayed a significant degree of improvement in terms of the structure and function of the heart and it’s blood vessels. Further studies published in 2003 and 2004 using the TOPCARE protocol with larger groups of patients have consolidated the results found in the 2002 study. Patients with ischaemia in the leg were also treated with endothelial progenitor cells with seeming success at improving blood perfusion and reducing pain.
Endothelial Stem Cells and Exercise
Exercise appears to increase the mobilization and activity of endothelial stem cells, as do statins, whereas various risk factors for coronary artery disease have an inhibitory effect. The presence of endothelial stem cells in the blood does not however guarantee their ability to effect change in the blood vessel walls as there are a complex array of signalling events required to allow the cells to migrate to the right location and adhere to the existing vasculature, as well as to effect differentiation into endothelial cells themselves.
Systemic Sclerosis and Stem Cells
Those with early stage systemic sclerosis were found to have high circulating levels of endothelial stem cells, most likely as an initial attempt by the body at repairing itself (Nevskaya, et al, 2008). As disease persisted, and progressed, the levels of endothelial stem cells decreased, endothelial dysfunction occurred, along with capillary loss, which was associated with pulmonary hypertension and serious cardiac disease. Those with lower levels of HDL (the so-called ‘good’ cholesterol) had a tendency to have low endothelial progenitor cells in the Nevskaya study, although this has not been investigated or confirmed by other research. One study found that smokers had significantly lower levels of circulating endothelial stem cells which predisposed them to coronary artery disease (Vasa, et al, 2001).
Endothelial cells, and their stem cells, have also been highlighted as a possible mechanism by which stroke patients may be treated through neurogenesis and angiogenesis for functional recovery. However, practical therapies are a long way off as the risks of undesirable vascular growth in the brain tissue remain too high for treatment to be thought appropriate in humans. Recent research at the University of Michigan has looked at the role of endothelial progenitor cells in cardiovascular disease in lupus patients (Kahlenberg, and Kaplan, 2011). It appears that interferon-alpha plays a role in inhibiting the differentiation of endothelial stem cells into endothelial cells to repair cardiovascular damage, which then results in progressive pathology (Kaplan, 2009).
References
Xiong Y, Mahmood A, Chopp M., Angiogenesis, neurogenesis and brain recovery of function following injury, Curr Opin Investig Drugs. 2010 Mar;11(3):298-308.
Vasa M, Fichtlscherer S, Aicher A, Adler K, Urbich C, Martin H, Zeiher AM, Dimmeler S., Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease, Circ Res. 2001 Jul 6;89(1):E1-7.
Nevskaya T, Bykovskaia S, Lyssuk E, Shakhov I, Zaprjagaeva M, Mach E, Ananieva L, Guseva N, Nassonov E., Circulating endothelial progenitor cells in systemic sclerosis: relation to impaired angiogenesis and cardiovascular manifestations, Clin Exp Rheumatol. 2008 May-Jun;26(3):421-9.
Schächinger V, Assmus B, Britten MB, Honold J, Lehmann R, Teupe C, Abolmaali ND, Vogl TJ, Hofmann WK, Martin H,Dimmeler S, Zeiher AM., Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCARE-AMI Trial, J Am Coll Cardiol. 2004 Oct 19;44(8):1690-9.
Assmus B, Schächinger V, Teupe C, Britten M, Lehmann R, Döbert N, Grünwald F, Aicher A, Urbich C, Martin H, Hoelzer D,Dimmeler S, Zeiher AM., Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI), Circulation. 2002 Dec 10;106(24):3009-17.
Britten MB, Abolmaali ND, Assmus B, Lehmann R, Honold J, Schmitt J, Vogl TJ, Martin H, Schächinger V, Dimmeler S, et al., Infarct remodeling after intracoronary progenitor cell treatment in patients with acute myocardial infarction (TOPCARE-AMI): mechanistic insights from serial contrast-enhanced magnetic resonance imaging. Circulation. 2003 Nov 4; 108(18):2212-8. Epub 2003 Oct 13.
Schächinger V, Assmus B, Britten MB, Honold J, Lehmann R, Teupe C, Abolmaali ND, Vogl TJ, Hofmann WK, Martin H,Dimmeler S, Zeiher AM., Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCARE-AMI Trial, J Am Coll Cardiol. 2004 Oct 19 ;44(8):1690-9.
Kahlenberg JM, Kaplan MJ., The interplay of inflammation and cardiovascular disease in systemic lupus erythematosus, Arthritis Res Ther. 2011 Feb 28;13(1):203. [Epub ahead of print]
Kaplan MJ., Premature vascular damage in systemic lupus erythematosus: an imbalance of damage and repair? Transl Res. 2009 Aug; 154(2):61-9. Epub 2009 Jun 17.
