IT鈥橲 A claim that could profoundly affect the future of stem cell research. 快猫短视频s at biotech giant Genzyme say that many supposedly different kinds of adult stem cells 鈥� which hold enormous promise for treating disease 鈥� are in fact indistinguishable.
The experiments appeared in a little-noticed paper late last year (Tissue Engineering, vol 8, p 739), but are now gaining attention. If the conclusions are correct 鈥� and this is far from settled 鈥� those in the field may be in for quite a ride. At issue are basic questions about how many different types of adult stem cells there are, what they are capable of and how to distinguish between them, not to mention who owns the patent rights.
Because adult stem cells are present in everyone, they are easier to obtain than the embryonic stem cells taken from 10-day-old embryos, and far less controversial. Until recently, however, it was thought they had only limited potential.
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That changed last year, when 快猫短视频 revealed that Catherine Verfaillie of the University of Minnesota had discovered 鈥渕ultipotent adult progenitor cells鈥�, or MAPCs, apparently capable of giving rise to all tissues in the body, just like embryonic stem cells (26 January 2002, p 4). The work was later published in Nature.
Such cells could be taken from an individual and used to generate any kind of tissue needed by that person, such as muscle tissue for repairing damaged hearts.
Another promising kind of adult stem cell is Osiris Therapeutics鈥� mesenchymal stem cell. MSCs have only been shown to make a handful of tissues such as bone, cartilage, fat and muscle, but have a remarkable property: they seem to cause little or no immune reaction when transplanted (快猫短视频, 15 December 2001, p 4). That means stem cells from one person could be used to treat many others, instead of each individual having to be treated with their own cells.
But according to Ross Tubo of Genzyme, the MAPCs and MSCs are one and the same. This has enormous implications. Put the properties of the two kinds of cell together and all of a sudden you have a non-controversial, highly versatile source of adult stem cells that can, in theory, be transplanted to anyone, because the cells don鈥檛 trigger an immune reaction. This truly would be the ultimate stem cell.
The legal repercussions of Genzyme鈥檚 claims could also be profound. Osiris already has several patents on MSCs and some of their medical applications, while Verfaillie has a pending patent application on MAPCs. What if they are the same cell? 鈥淥nly one [group] can get a valid patent to the thing itself,鈥� says British patent attorney Andrew Sheard. 鈥淚f it really is the same thing it doesn鈥檛 sound hopeful for the second group.鈥�
When Genzyme started looking at the potential of stem cells from different labs, one thing became clear: 鈥淧eople weren鈥檛 using the same set of tools to evaluate their cells,鈥� says Tubo. His team therefore set out to devise a systematic way of comparing different types of adult stem cells.
They harvested bone marrow from volunteers and followed the methods published by Osiris, Verfaillie and others to obtain stem cells. According to Tubo, all cell preparations had the same 12 proteins on the cell surface, and behaved in the same way when coaxed down the nerve or cartilage pathways. His conclusion: 鈥淭hey were indistinguishable.鈥�
But not everyone agrees. Looking at 12 markers and two cell fates does not justify conclusions of such magnitude, says stem cell biologist Leonard Zon of Harvard University. 鈥淚t鈥檚 far from settled,鈥� he says. 鈥淚鈥檇 love for it to be simple, but it鈥檚 not.鈥�
There is also debate over a seemingly small, but potentially important change in the method that Genzyme used to obtain MAPCs. A key step in obtaining MAPCs, according to Ohio-based Athersys, the company that has licensed the technology, is to grow bone marrow cells at a very low density. Yet Tubo鈥檚 team obtained nothing this way and instead grew cells at a high concentration.
So when Tubo claims his MAPCs behave like MSCs, Athersys contends it is because they actually were MSCs. The company admits the MAPC technique is tricky, but say it can be done and that MAPCs obtained this way are different to MSCs. Verfaillie鈥檚 group says there are clear differences in gene expression between their MAPCs and MSCs, for instance.
But even if Tubo didn鈥檛 get true MAPCs with his culture method, he does seem to have grown a cell that blurs the line between MAPCs and MSCs. Tubo says he can get the cells to differentiate into various cell types not previously achieved with MSCs, yet like MSCs the cells seem not to trigger immune rejection.
Genzyme is 鈥渃ontinuing full steam ahead鈥� to develop clinical applications of the cells. But why would a major biotech company spend money on cells that another company has already patented? According to Tubo, his team harvested some stem cells using methods published decades ago, and these cells had the same properties too. While Tubo would say no more, it may be that Genzyme thinks the existing patents might be invalid or could be bypassed, which would open up the field to all and sundry.
