July 24, 2013

expert reaction to a new study refuting the evidence for VSELs

 A study published in Stem Cell Reports has refuted the evidence and clinical potential for Very Small Embryonic-like Stem Cells (VSELs).  

Professor Robin Lovell-Badge, Head of Developmental Genetics, MRC National Institute for Medical Research, said:

“I have always thought it odd how some will think it “ethical” to propose to use cells for therapy that have a rather dubious provenance. These range from embryonic stem (ES) cells derived from “dead” embryos, or from parthenogenetic embryos, spermatogonial stem cells (where both the latter are known to have abnormal parental imprinting), and to other cells types that are claimed to have properties that just don’t quite make sense or fit with our knowledge of embryology, such as supposedly pluripotent cells from the amnion. Research on these tend to be popular in countries where there is strong opposition to embryonic stem cells obtained from normal preimplantation embryos, notably those left over from in vitro fertilisation and are therefore not required for reproductive purposes.

 “To me at least, VSELs were always the oddest of these alternatives. These Very Small Embryonic Like cells were proposed to exist in a number of adult tissues, notably the bone marrow, and to be characterised by their size, 3-5 µm, which is smaller than almost any other cell type in the body (sperm being smaller), a particular combination of cell surface markers which aided their isolation, and to be able to give rise to any other cell type in the body, i.e. to be pluripotent.

 “Their size alone is weird, but one well known property of pluripotent cells, indeed it is one of the tests of their pluripotency, is their ability when placed in ectopic sites (meaning outside their normal location in the early embryo) to give rise to tumours, called teratocarcinomas. These are made up of undifferentiated cells and a random mixture of their differentiated derivatives corresponding to a wide range of cell types, including, nerves, skin, gut, muscle, cartilage, etc. If VSELs are pluripotent, and located in various parts of the body that would constitute ectopic sites for an ES cell, why do we not all have teratocarcinomas ? In other words if there really were these funny small cells swimming round our body that were very pluripotent then we should already be very aware of their existence from the presence of these tumours and from the differentiation of specialised cells in the wrong places.

 “Irv Weissman is a champion of well conducted research in the stem cell field. In the current paper, which is a very well-designed study, his lab has followed the protocols for the isolation of these cells as described by VSEL advocates. First, they could not find any viable cells of the appropriate small size. Using two different types of cell sorter, and another machine that just analyses rather than sorts cells, the only objects of 3-5 µm diameter were just cell fragments or debris.  Cells with the appropriate combination of cell surface markers (which can be detected by specific antibodies) could be isolated, but these were larger. The authors are generous in conceding that the VSEL proponents may have underestimated the size of these cells.  But they then go on to test their properties, but fail to find any that that are able to differentiate into cells of the blood system, which would be a (minimal) prerequisite for calling a cell pluripotent.

 “This current paper joins several others that have also failed to find the existence of VSELs, and these all stand in distinct contrast to those from the proponents of VSELs. One explanation for the difference would be if the latter have not given sufficient details of the methodology in their papers. This in itself would be a problem as the ability to reproduce experiments is essential to give confidence in scientific results. VSELs have not sparked much interest amongst many stem cell scientists, and the current paper from the Weissman lab is unlikely to help. And while negative results do not necessarily disprove a hypothesis, this should be of concern to funders, such as the Vatican, hoping to avoid ethical dilemmas, but wasting their money on an avenue of research that now seems very unlikely to lead anywhere, on cells that might not even exist.

 “VSELs make little sense biologically and it’s hard not to conclude that those researchers who support their existence have ideological rather than science based reasons for pursuing them. Even if they do exist they cannot have the properties of ES cells, and would therefore be less useful for potential cell based therapies. Moreover, would you really want to put something in your body that has not been described in detail let alone understood, and that can’t even be tested by one of the best stem cell labs in the world?”               

‘Do pluripotent stem cells exist in adult mice as very small embryonic stem cells?’ by Dr. Irving Weissman et al. was published in Stem Cell Reports