A strong argument exists for using fetal cells as tissue grafts totreat neurodegenerative diseases, notably Huntington's,Parkinson's and Alzheimer's. And there is also a strongargument against such an approach. Canadian neuroscientistSamuel Weiss suggests a way around this controversy: "Growyour own fetal cells."
Weiss, who teaches anatomy, pharmacology and therapeutics atthe University of Calgary, has patents pending in the U.S. andEurope on "Novel Growth Factor-Responsive Progenitor CellsWhich Can be Proliferated in Vitro." Late last month, the WorldIntellectual Property Organization in Europe published Weiss'international application. It sets forth his methods andmaterials for a culture system that "perpetuates an unlimitednumber of fetal neural progenitor cells."
These "allow for production of a large supply of tissue from aminimal number of fetuses, for transplantation into an animalwith neurodegeneration."
The patent text expressly states, however, that "the use ofjuvenile and adult cells for generating progenitors wouldeliminate the ethical problem of obtaining fetal neuronaltissue." It would also obviate problems of tissue rejection anduse of immunosuppressive drugs in alleviating the symptomsof neurodegenerative diseases and trauma.
Last July, Weiss and his co-inventor, Brent Reynolds, enteredinto a collaborative research agreement with CytoTherapeuticsInc. (CTI) of Providence, R.I., to test their continuouslyproliferating neural stem cells in CTI's immunity-shieldedcapsule delivery system. The Calgary neuroscientists thereuponsupplied CTI with their stem cell cultures, under exclusiveevaluation and optioning rights for one year. At that time, SethRudnick, CTI's president and chief executive officer, toldBioWorld that obtaining access to their stem cells "is ultimatelythe best way to evaluate our technology."
Since filing their initial application to the U.S. Patent andTrademark Office on July 8, 1991, Weiss and Reynold'sresearch has progressed from in vitro cell culture to as-yet-unpublished in vivo experiments in mice and rats. Weiss willdiscuss these next Tuesday in a talk to the prestigious MontrealNeurological Institute. "I will outline what we consider a novelconcept," he told BioWorld, "manipulation of central nervoussystem cells in vitro and in vivo as an avenue fro brain repair."The institute, he noted is a designated worldwide "center ofexcellence on neural regeneration."
To grow function-specific nerve cells that innervate variousparts of the nervous system, Weiss and Reynolds began byculturing in recombinant epidermal growth factor progenitorstem cells derived from cerebellum, cortex, septum, thalamus,spinal cord and mid-brain of embryonic mice. Otherrecombinant polypeptide growth factors in their culturemedium then regulated the proliferation and differentiation ofthese neuronal precursors of mammalian cells.
These progenitors differentiated into the three major types ofcentral nervous system cells: neurons, astrocytes andoligodendrocytes, which the Calgary researchers can now churnout in unlimited quantities. Weiss said that "in vitro, cells withneuronal morphology express immunoreactivity for GABA,substance P and methionine-enkephalin -- three principalneurotransmitters of the adult striatum."
Their collaborators at other universities, Weiss said, "haveverified in animal experiments "that these cells can bereimplanted in damaged or lesioned or genetically modifiednerve tissues to replace cells that have been lost to injury ordisease." To prove the feasibility of this cell replacementtherapy, they injected selective neurotoxins into the striatalareas of rat or mouse brains, to wipe out a given population ofcells responsible for synthesizing and releasing a specificneurotransmitter -- GABA in Parkinson's, for example -- theninjected their cultured cells. "It appeared that multiple celltypes survived, and their identification is under way," Weisssaid.
"Most recently," he told BioWorld, "we have very goodpreliminary evidence that a human counterpart to these cellsexists, which can be induced to proliferate in similar fashion,though not identically, to what we have reported for a mouse."
Weiss reiterated what his patent application mentions inpassing: that "the adult brain may serve as an alternativesource of neuroepithelial stem cells isolated from fetal braintissue."
Neuroscientist Fred Gage of the University of California, SanDiego, finds the Calgary cells "a very interesting and importantdiscovery, and likely to have a significant impact on the way inwhich neuronal cells are cultured in vitro." Gage researchesbrain and central nervous system repair, "looking among avariety of techniques for those that work," he told BioWorld.
Will Weiss' method work in therapeutic practice? "It will takemore research to characterize his cells and determine theirsurvivability in vivo before we can assess their application intherapy," said Gage. "So far, all we really know about them isthat they grow in a dish."
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.