By Nuala Moran
BioWorld International Correspondent
LONDON As the row over therapeutic cloning rumbles on, the reality is that stem cells from other sources are well on the way to providing ways of replacing, repairing, regenerating and rejuvenating damaged tissues.
We are in the midst of a medical paradigm shift, Dan Passeri, president and CEO of Curis Inc., told a session on the therapeutic realities of stem cells Tuesday at the second annual BioIndustry Association CEO and Investor Conference held here. The human body has reservoirs of cells that can replace and repair damaged tissues, and we are discovering the mechanisms for doing this outside the body and [uncovering] the factors that get stem cells to go down the desired pathways.
Stem cells are very complex systems that respond to a wide range of cues. Although adult stem cells are rare (about one in 100,000 cells), it is now becoming clear that they can be driven down different routes to differentiate different cell types.
If we learn how to manipulate adult stem cells we could derive many therapies from them, Passeri said. For example, Curis has discovered how to drive adult skin stem cells to become neuronal cells, glial cells, dopaminergic neurons and smooth muscle cells and oligodendrocytes, and is looking at therapeutic applications in diseases including Parkinsons and myocardial infarction.
Skin is readily available and minimally invasive to collect, he said. The cells can be propagated for one year without differentiating in culture, and we have already discovered how to differentiate them into a range of different cell types.
Stem cell research also is providing important tools for drug discovery and a source of novel targets.
The pathways cells go down and what factors stimulate them to do it are going to be very important in drug discovery, Passeri said. Stem cells also could provide an important delivery mechanism for gene therapy, especially in treating neurodegenerative diseases, because when introduced into the brain they migrate to the sites of damage.
Depending on what they are required to do, stem cells can be introduced in an undifferentiated form to a tissue niche that has the capacity to induce differentiation. This replicates what the body does naturally when it responds to traumas such as mending a broken bone or healing a wound. On the other hand, in slow-developing diseases such as Parkinsons or Type I diabetes, the damaged tissues do not have the conditions in place to differentiate precursor cells, and cells must be differentiated outside the body.
Dan Marshak, vice president at Cambrex Corp., said it was previously thought that adult stem cells had tissue restrictions. However, it is now becoming clear they can be differentiated into multiple different lineages; they are certainly multipotent, and are possibly pluripotent.
He pointed out that hematopoietic stem cells, adult cells taken from bone marrow, already are in widespread use for therapy, while Osiris Therapeutics, of Baltimore (where Marshak was previously employed), has a number of adult stem cell-derived therapeutics in clinical development, including OsteoCel, a bone regeneration therapy in Phase II in head and neck cancer; Allogen, a suspension of human mesenchymal stem cells being used in transplants to promote blood cell recovery and minimize graft-vs.-host disease; Chondrogen, a cartilage replacement therapy, which is due to enter Phase I early in 2002; and CardioCel, for improving cardiac function after heart attacks, which is just completing preclinical development.
In other words, adult-derived stem cells are now entering late-stage trials for the repair of bone, cartilage and muscle.
Martin Edwards, of ReNeuron Ltd. in London, a cell therapy company focused on neurodegenerative diseases, pointed out that human neural stem cells can be derived from embryonic, fetal and adult sources. But, he said, No one has a clue as to which source of cells will prove best in the clinic.
ReNeuron has developed conditionally immortalized cell lines that divide at 33 degrees C in culture, but at 37 degrees C stop dividing and differentiate. In an animal model of stroke, these cells migrate to damaged areas of the brain and repopulate them.
Edwards noted that cell therapy into the brain is already a therapeutic reality. The practicality of the procedures, of how to get the cells in, is established. It can be done with local anaesthetic and the patient goes home the next day.
However, he said the practical issues involved in the development of stem cell therapy should not be minimized. There really is no regulatory precedent, and there are many regulatory issues to be considered. I believe they are surmountable, but they should not be underestimated.
Michael Ruhl, CEO of Cardion AG, said sources of stem cells are already commoditized and the next step is to develop an industrial approach to culturing them that is economic and meets regulatory requirements. Cardion has developed technology for stem cell gating, which pushes embryonic stem cells down the required route, eliminating other cell types and producing very pure cultures. The company can also educate the stem cells to reproduce at very fast rates.
The immune response to cell therapy varies according to the application but in cases where a reaction is likely, Cardion has a method for reprogramming the recipients immune system to selectively ignore the cell implant.
Overall, we can see that the key technologies are solidifying, but we will need the usual clinical development time, Ruhl said. The full power of stem cell technology to revolutionize major pharmaceutical markets is not there yet. However, we are setting the pace for regulatory approval and clinical acceptance.
Ruhl thinks therapeutic cloning will never become a reality. It is an ethically questionable procedure, but apart from that, it is difficult to make safe. It would take time to do this, and the material is only suitable for one person.