Blood Vessel Cells from Embryonic Stem Cells: Catch Up, Not Breakthrough

Date: 04/02/2002

Once again, an alleged advance using embryonic stem cells is being hyped in the media as a major scientific breakthrough, when in fact it merely repeats earlier, and more successful advances using adult stem cells and other alternatives. Moreover, the alleged breakthrough is being hyped at the expense of ignoring or misrepresenting these alternatives.

This time, according to recent news reports, embryonic stem cells have been transformed into endothelial (blood vessel) cells and small blood vessels. Dr. Robert Langer of MIT, is quoted as saying “This is the first time this has been done with human cells” (“Blood Vessels Made From Stem Cells”, AP Online, 03/25/02). Another report says “But to date, adult stem cells have not come close to spontaneously forming blood vessels, as Langer’s embryonic stem cells did.” (“Stem cells converted to functioning blood vessels,” Boston Globe, 3/26/2002).

These assertions are simply wrong, and can only be the result of ignorance of the significant peer-reviewed literature that shows otherwise.

The report may be the first to show that human embryonic stem cells might be able to form blood vessels. However, it IS NOT the first time human stem cells have been used to form blood vessel cells and blood vessels.

Adult stem cells from humans and animals have already shown the ability to stimulate new blood vessel formation, both spontaneously in culture as well as when injected into animals (most recently by a group from the University of Minnesota, M. Reyes et al.; “Origin of endothelial progenitors in human postnatal bone marrow;” Journal of Clinical Investigation 109, 337-346; February 2002). This ability of adult stem cells to participate in the formation of new blood vessels has been known for several years. Furthermore, the new embryonic stem cell study is even behind what is now being done in human patients using no new cells at all, but only the injection of growth factors and gene therapy that stimulates growth of new blood vessels by the body itself, to restore circulation to the heart and limbs.

Following are some of the more important studies in this regard:

ADULT STEM CELLS AND NEW BLOOD VESSEL FORMATION

M. Reyes et al.; “Origin of endothelial progenitors in human postnatal bone marrow;” Journal of Clinical Investigation 109, 337-346; February, 2002. [HUMAN bone marrow stem cells transformed into blood vessels in culture and in animals. From the paper: “[C]ulture of MAPC-derived endothelial cells on extracellular matrix resulted in vascular tube formation within 6 hours.”]

S. Kaushal et al.; “Functional small-diameter neovessels created using endothelial progenitor cells expanded in vitro,” Nature Medicine 7, 1035–1040; September 2001.

K. Shimizu et al.; “Host bone-marrow cells are a source of donor intimal smooth-muscle-like cells in murine aortic transplant arteriopathy,” Nature Medicine 7, 738-741; 2001.

A. Kawamoto et al.; “Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia,” Circulation 103, 634-637; 2001 [Human cells used]

J. Li et al.; “Vascular smooth muscle cells of recipient origin mediate intimal expansion after aortic allotransplantation in mice.” American Journal of Pathology, 158, 1943-1947; 2001.

D. Orlic et al.; “Mobilized bone marrow cells repair the infarcted heart, improving function and survival,” Proceedings of the National Academy of Sciences USA 98, 10344-10349; August 28, 2001.

K.A. Jackson et al., “Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells,” Journal of Clinical Investigation 107, 1395-1402; June 2001.

D. Orlic et al.; “Bone marrow cells regenerate infarcted myocardium,” Nature 410, 701-705; April 5, 2001.

A.A. Kocher et al.; “Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function,” Nature Medicine 7, 430-436; April 2001. [bone marrow from adult humans used to directly induce new blood vessel formation in rats]

T. Takahashi et al.; “Ischemia- and cytokine-induced mobilization of bone-marrow derived endothelial progenitor cells for neovascularization,” Nature Med. 5, 434-438; 1999.

D. Shum-Tim et al.; “Tissue engineering of autologous aorta using a new biodegradable polymer;” Ann. Thorac. Surg. 68, 2298-2304; December 1999.

Q. Shi et al.; “Evidence for Circulating Bone Marrow-Derived Endothelial Cells;” Blood 92, 362-367; July 15, 1998.

T. Asahara et al.; “Isolation of Putative Progenitor Endothelial Cells for Angiogenesis” Science 275, 964-967; Feb. 14, 1997.

GENE THERAPY AND GROWTH FACTORS FOR NEW BLOOD VESSELS IN PATIENTS

J.M Isner, “Myocardial gene therapy,” Nature 415, 234-239; January 10, 2002.

P.R. Vale et al.; “Randomized, single-blind, placebo-controlled pilot study of catheter-based myocardial gene transfer for therapeutic angiogenesis using left ventricular electromechanical mapping in patients with chronic myocardial ischaemia,” Circulation 103, 2138-2143 (2001).

P.R. Vale et al.; “Left ventricular electromechanical mapping to assess efficacy of phVEGF165 gene transfer for therapeutic angiogenesis in chronic myocardial ischemia,” Circulation 102, 965-974 (2000).

T.K. Rosengart et al.: “Angiogenesis gene therapy. Phase I assessment of direct intramyocardial administration of an adenovirus vector expressing VEGF121 cDNA to individuals with clinically significant severe coronary artery disease,” Circulation 100, 468-474 (1999).

I. Baumgartner et al.; “Constitutive expression of phVEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia,” Circulation 97, 1114-1123 (1998).

D.W. Losordo et al.; “Gene therapy for myocardial angiogenesis. Initial clinical results with direct myocardial injection of phVEGF165 as sole therapy for myocardial ischemia,” Circulation 98, 2800-2804 (1998).

{
Adult/73
|
Embryonic/0
}