Treating Disease With Adult Stem Cells And Embryonic Stem Cells

Date: 03/02/2002

“[Embryonic] stem cells could be used to make up for the deficits in brain and pancreas cells that cause Parkinson’s disease or diabetes. It is the only present hope that those who suffer from these ailments have” (emphasis added).

— David Baltimore, Nobel laureate and President, California Institute of Technology, Wall Street Journal, 7/30/01.

“With [embryonic stem cells], I have no doubt I can be cured. I have virtually no doubt I could walk again as my spinal cord has not been cut and my injury is confined in one very small area. It’s my big chance.”

— Christopher Reeve, actor and executive director, The Christopher Reeve Paralysis Foundation, This is London, 2/27/02


Is embryonic stem cell research really “the only present hope” for those suffering debilitating diseases? Such extravagant claims are not substantiated in the scientific literature.

Following are three areas – Parkinson’s, spinal cord repair and diabetes — often referred to as examples of the successful use of embryonic stem cells and their future therapeutic potential. But even at their most successful, embryonic stem cells are eclipsed by adult stem cells in the treatment of disease.

Parkinson’s Disease
Adult Stem Cells

Injection of growth protein into brains of Parkinson’s rats caused their neural stem cells to grow, migrate to the site of damage, and begin to replace missing nerve cells. Eighty percent (80%) of the rats received a benefit from the treatment, with no tumor formation.

Reference
J. Fallon et al.; “In vivo induction of massive proliferation,directed migration, and differentiation of neural cells in the adult mammalian brain,” Proc. Natl. Acad. Sci. USA 97, 14686-14691; December 19, 2000

Embryonic Stem Cells

Parkinson’s rats injected with mouse embryonic stem cells showed a modest benefit for just over 50% of the rats, but one-fifth (20%) of the rats died of brain tumors caused by the embryonic stem cells.

Reference
L.M. Bjorklund et al.; “Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model,” Proc. Natl. Acad. Sci.USA
www.pnas.org/cgi/doi/10.1073/pnas.022438099
(PNAS Early Edition) Jan 8, 2002

Spinal Cord Regeneration
Adult Stem Cells

In animal studies, several labs have shown that adult stem cells are capable of re-growth and reconnection in spinal cord injury, allowing functional recovery.

Adult stem cell transplants “promote functional recovery of paraplegic adult rats and long-distance motor axon regeneration in their completely transected [severed] spinal cords,” and showed “dramatic functional improvement and anatomical repair” (Ramon-Cueto et al; 2000).

Others, using either transplanted adult stem cells or injection of normal growth proteins to stimulate existing adult stem cells, achieved re-growth of neurons and re-myelination (sheathing) of neurons.

Eighteen-year old Melissa Holley, a paraplegic patient with a severed spinal cord, has been treated with her own immune cells, and has regained movement of her toes and bladder control. (no peer-reviewed paper yet; Globe and Mail (Toronto), June 15, 2001]

References
M. Sasaki et al., “Transplantation of an acutely isolated bone marrow fraction repairs demyelinated adult rat spinal cord axons,” Glia 35, 26-34; July 2001

A. Ramon-Cueto et al., “Functional recovery of paraplegic rats and motor axon regeneration in their spinal cords by olfactory ensheathing glia,” Neuron 25, 425-435; February 2000.

M.S. Ramer et al.; “Functional regeneration of sensory axons into the adult spinal cord,” Nature 403, 312-316; January 20, 2000S. Shihabuddin et al.; “Adult spinal cord stem cells generate neurons after transplantation in the adult dentate gyrus,” J Neuroscience 20, 8727-8735; December 2000.

Barnett et al.; “Identification of a human olfactory ensheathing cell that can effect transplant-mediated remyelination of demyelinated CNS axons,” Brain 123, 1581-1588, August 2000

A. Ramon-Cueto et al., “Long-distance axonal regeneration in the transected adult rat spinal cord is promoted by olfactory ensheathing glial transplants,” J Neuroscience 18, 3803-3815; May 15, 1998

Embryonic Stem Cells

A study by McDonald et al. study showed some functional improvement in rats with spinal cord injury, slightly better than no treatment alone.Studies by Liu et al. and Brüstle et al. showed that ES cells could form protective myelin sheaths around nerves in rats with spinal cord, but they did not show or test for any functional recovery of the animals.

References
J.W. McDonald et al., “Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord,” Nature Medicine 12, 1410-1412, December 1999

S. Liu et al., “Embryonic stem cells differentiate into oligodendrocytes and myelinate in culture and after spinal cord transplantation,” Proc. Natl. Acad. Sci. USA 97, 6126-6131; May 23, 2000

O. Brüstle et al., “Embryonic Stem Cell-Derived Glial Precursers: A Source of Myelinating Transplants,” Science 285, 754-756, July 30, 1999

Diabetes
Adult Stem Cells

Scientists “retrained” immune cells to reverse diabetes in mice. The autoimmunity that was previously directed against insulin-secreting cells was reversed, and adult stem cells in the mice formed insulin-secreting cells. The treatment was “…thus able to effect an apparent cure of established Type 1 diabetes in the [diabetic] mouse” (S. Ryu et al.).

Pancreatic adult stem cells grown in culture formed insulin-secreting islets. When injected into diabetic mice, the mice survived without further need of insulin injections.

Scientists at Harvard Medical School cultured human pancreatic ductal cells under specific conditions, inducing the cells to form islet buds and secrete insulin. “Thus, duct tissue from human pancreas can be expanded in culture and then be directed to differentiate into glucose responsive islet tissue in vitro. This approach may provide a potential new source of pancreatic islet cells for transplantation”

References
S. Ryu et al.; “Reversal of established autoimmune diabetes by restoration of endogenous ß cell function,” J. Clin. Invest. 108, 63-72; July 2001

V.K. Ramiya et al.; “Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells,” Nature Medicine 6, 278-282, March 2000.

S. Bonner-Weir et al.; “In vitro cultivation of human islets from expanded ductal tissue,” Proc Natl Acad Sci USA 97, 7999-8004; July 5, 2000.

Embryonic Stem Cells

Researchers reported the apparent conversion of mouse embryonic stem cells into insulin producing pancreatic islet cells. The mouse embryonic stem cells secreted only 1/50th the normal amount of insulin, and diabetic mice implanted with the cells still died.

Reference
N. Lumelsky et al.; “Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets,” Science 292, 1389-1394; May 18, 2001

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