Billions and Billions of stem cells (or ACT kills more mice needlessly)

Once again, ACT is hyping research that duplicates work already done using non-embryonic stem cell research. The only thing new is the possibility that they have come up with a way to make "Billions" of the plastic cells.

Ok, maybe we learned something from Advanced Cell Technology's Robert Lanza's latest human embryonic stem cell report published on line (free) prior to print in Nature Methods, "Generation of functional hemangioblasts from human embryonic stem cells." Perhaps the method of growing the cells without animal or human serum will prove useful.

This time, ACT is hyping their development of "hemangioblasts," the stem cells that become blood cells and the cells that make up the blood vessels, and the big claim is that the researchers at Advanced Cell Technology have a technique for making "billions and billions" of cells. Their own introduction explains that the group has not developed a new line of cells or proven anything new as far as vascular repair goes:

Although progenitor cells have recently been discovered that can enter the circulation in response to vascular injury and ischemia (1–5), defining and isolating these cells has proven problematic. Circulating bone marrow–derived cells have also been shown to be important in normal physiologic maintenance and repair of the body’s vasculature (6,7) with approximately 1–3% of endothelial cells at any one time being bone marrow–derived. Furthermore, the entire hematopoietic system has been hypothesized to originate from a transient population of hemangioblasts restricted to embryogenesis (8,9). But recent evidence suggests that hemangioblasts or more mature endothelial progenitors may also exist in adult tissues and umbilical cord blood (2–4,10,11).More direct proof for their existence was provided when the in vitro equivalent of the hemangioblast was isolated using a mouse embryonic stem cell differentiation system (12,13). Recently a human hemangioblast cell population derived from hES cells was also identified using a procedure that consisted of serum-free differentiation in a mixture of cytokines followed by expansion in serum-containing medium (14). To date, large-scale generation or functional assessment of hemangioblasts has not been achieved in any of these systems. Here we show that large numbers of what appear to be a distinct population of progenitor cells with both hematopoietic and vascular potential can be efficiently and reproducibly generated from hES cells using a simple two-step procedure with different supplements under fully serum-free conditions.

Here's those references, please note the titles:

1. Rafii, S. & Lyden, D. Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration. Nat. Med. 9, 702–712 (2003).
2. Grant, M.B. et al. Adult hematopoietic stem cells provide functional hemangioblast activity during retinal eovascularization. Nat. Med. 8, 607–612 (2002).
3. Bailey, A.S. et al. Transplanted adult hematopoietic stems cells differentiate into functional endothelial cells. Blood 103, 13–19 (2004).
4. Cogle, C.R. et al. Adult human hematopoietic cells provide functional hemangioblast activity. Blood 103, 133–135 (2004).
5. Otani, A. et al. Bone marrow-derived stem cells target retinal astrocytes and can promote or inhibit retinal angiogenesis. Nat. Med. 8, 1004–1010 (2002).
6. Crosby, J.R. et al. Endothelial cells of hematopoietic origin make a significant contribution to adult blood vessel formation. Circ. Res. 87, 728–730 (2000).
7. Hill, J.M. et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N. Engl. J. Med. 348, 593–600 (2003).
8. Wagner, R.C. Endothelial cell embryology and growth. Adv. Microcirc. 9, 45–75 (1980).
9. Park, C., Ma, Y.D. & Choi, K. Evidence for the hemangioblast. Exp. Hematol. 33, 965–970 (2005).
10. Loges, S. et al. Identification of the adult human hemangioblast. Stem Cells Dev. 13, 229–242 (2004).
11. Pelosi, E. et al. Identification of the hemangioblast in postnatal life. Blood 100, 3203–3208 (2002).
12. Choi, K., Kennedy, M., Kazarov, A., Papadimitriou, J.C. & Keller, G. A common precursor for hematopoietic and endothelial cells. Development 125, 725–732 (1998).
13. Kennedy, M. et al. A common precursor for primitive erythropoiesis and definitive haematopoiesis. Nature 386, 488–493 (1997).
(Emphasis is mine)

As I said, the main claim in the article is that the ACT researchers made a large number of hemangioblasts, and set about proving that they were, indeed, hemangioblasts, through experiments on mice, which all had induced injuries and which were sacrificed for autopsy.

However, what do we read in the tabloids science mags?

From Scientific American.
"New Recipe for Powerful Stem Cells Promises Greater Insight."

Other groups had discovered hemangioblasts in mouse and human embryonic cells as well as in adult human bone marrow and umbilical cord blood. But they were unable to harvest them in large enough numbers to evaluate the cells' healing properties.

And from Technology Review, "Stem Cells Repair Blood Vessels: A new method to boost growth of blood vessels with stem cells could improve cell therapies for diabetes and heart disease."

And last, but not least, from Reuters, UK, "Embryonic stem cells can repair eyes, company says."

"For example, we injected the cells into mice with damaged retinas due to diabetes or other eye injury. The cells (labeled green) migrated to the injured eye, and incorporated and lit-up the entire damaged vasculature. The cells are really smart, and amazingly, knew not to do anything in uninjured eyes."

The researchers killed the mice to check the cells' progress, so they do not know the long-term effects.

What none of the articles mention is the ongoing studies using non-embryonic stem cells to do what ACT claims its embryonic stem cells will do.

There was this report in the American Journal of Pathology in 2006 and this one from 2004, published in the Journal of Clinical Investigation about using a patient's own bone marrow cells to repair eye injury. Both used mouse models.

There is also the Austin, Texas trial that I reported on last week, which is using donor bone marrow cells. And there are several studies, including one using the patient's own stem cells to treat "Critical Ischemic Limb," at Houston, Texas' Stem Cell Center at St. Luke's Hospital.

It appears that this is just one more example of hype and hope about cells that have already been studied - and even used in humans - when someone (ACT, too often) claims to have a new study proving that they have generated human embryonic stem cells of some sort or other and to have "cured" some disease. (in mice, if at all.)

Texas researchers discover key to heart repair

Texas research team has published a report on the fusion of adult stem cells to damaged heart cells which enables healing of damage. In this case, the stem cells are from peripheral blood - the blood that circulates every day. Presumably, the origin of these cells is the bone marrow.

The review at Physorg.com. includes a discription of the current knowledge on heart repair and stem cells. Quoted is T.H.Yeh, M.D. one of the team from M. D. Anderson, the Texas Heart Institute at St. Luke's Episcopal Hospital and The University of Texas Health Science Center at Houston.

Because many of the drugs and therapies used to treat cancer can cause heart damage, M. D. Anderson, a world-renowned cancer therapy and research center, also invests in the study of heart disease.

Cardiac adult stem cells seem to do two different things: they divide to form blood vessels and they fuse to injured heart muscle cells or "cardiomyocytes" to cause the muscle cells to demonstrate "stemness." The original fused cells are now like very special stem cells that are cardiomyocytes that can divide and multiply for months, in order to repair the damage in the heart. Until recently, we were taught that heart muscle cells did not replicate and replace themselves in adults.

Yeh and his co-workers report on adult heart stem cells, three specific proteins, the mechanisms that stimulate their production, and evidence as to how these proteins and stem cells work after heart muscle damage. Two of the proteins, described as "sticky" similar to the two tapes in Velcro, are newly discovered by the team. Another protein, vascular endothelial growth factor or VEGF, was previously known to aid in the development of new blood vessels. In hearts, VEGF causes some of the stem cells to produce blood vessels rather than fuse to the damaged muscle cells. By a series of experiments using antibodies against the proteins in immune deficient mice with induced heart damage, the team has demonstrated one way the heart repairs itself and that the same adult stem cells can lead to new heart blood vessels and new heart muscle cells. The hope is that this discovery will allow us to increase the amount of repair in heart attack patients.

The abstract of the original article published in Circulation Research OnLine First, is available for free, here. The supplemental data and some figures are also available free, here.

The last author of the original article is James Willerson, M.D., the President of the University of Texas Health Science Center at Houston, and the man who went off to Brazil in order to do one of the first studies of bone marrow stem cells used to treat heart disease. He's been mentioned on this blog, here and here.
Unfortunately, Willerson is often quoted advocating the creation of new embryonic stem cell lines, and the destruction of more and more human embryos in order to harvest those lines.