脑细胞移植伴随控制性释放的生长因子在大鼠中被显示
WESTPORT, CT (Reuters Health) - Researchers at Cornell University have developed a transplantation system that allows control of fetal brain cell survival and differentiation by preassembly of "neo-tissue" in which fetal cells, synthetic matrix elements, and controlled-release protein are fused to mimic the microenvironment of developing tissue.
Drs. W. Mark Saltzman and Melissa J. Mahoney, in Ithaca, New York, first enzymatically dissociated fetal rat brain cells, resulting in a mixture of differentiated cells that resembled neurons and glia. In a separate step, they produced microparticles from poly (lactide-co-glycolide) in which nerve growth factor (NGF) and agents to alter its release were encapsulated.
, 百拇医药
As reported in Nature Biotechnology for October, the suspended cells and microparticles were incubated together in a rotary shaker. The Cornell researchers speculate that "microspheres are entrapped within aggregates by nonspecific electrostatic interactions between the cell glycocalyx and the microparticle surface."
The resulting neo-tissues were transplanted into the brains of healthy adult rats. Transplanted cells and microparticles remained at the site of transplantation. Subsequent examinations of sections of brain tissue showed increasing levels of NGF during the first 7 days, followed by reduction in NGF levels after 21 days.
, 百拇医药
Choline acetyltransferase levels remained elevated during the 21 days, indicating that "biologically active NGF is released from the synthetic microparticles at levels sufficient to affect cholinergic cell survival and/or differentiation."
"When we stopped the experiment at 21 days, the NGF was gone, but the effect on the tissue was still present, so it is not clear how the rate of protein release is related to the function of the tissue," Dr. Saltzman told Reuters Health. "We think that longer release will help. In our previous results with NGF, we have made materials that last for up to 2 months. With other proteins--antibodies, in particular--we have made polymeric systems that last for several years."
, http://www.100md.com
Drs. Mahoney and Saltzman suggest that one possible application of their technique would be to target microparticles to specific cell populations within the neo-tissue. An example would be to coat the microparticles with n-cadherin to target NGF sources to neurons.
They also recommend combining microparticles that release agents promoting distinct aspects of transplanted cell function, such as axon guidance, intracellular signaling, or immune response modification. This would make the neo-tissues specific for the treatment of neurodegenerative diseases and spinal cord injuries.
Dr. Saltzman added, "One other application where we think that this might be useful is in diabetes treatment, for which we could make neo-tissues from pancreatic cells."
Nat Biotechnol 2001;19:934-939.
-Westport Newsroom 203 319 2700, 百拇医药
Drs. W. Mark Saltzman and Melissa J. Mahoney, in Ithaca, New York, first enzymatically dissociated fetal rat brain cells, resulting in a mixture of differentiated cells that resembled neurons and glia. In a separate step, they produced microparticles from poly (lactide-co-glycolide) in which nerve growth factor (NGF) and agents to alter its release were encapsulated.
, 百拇医药
As reported in Nature Biotechnology for October, the suspended cells and microparticles were incubated together in a rotary shaker. The Cornell researchers speculate that "microspheres are entrapped within aggregates by nonspecific electrostatic interactions between the cell glycocalyx and the microparticle surface."
The resulting neo-tissues were transplanted into the brains of healthy adult rats. Transplanted cells and microparticles remained at the site of transplantation. Subsequent examinations of sections of brain tissue showed increasing levels of NGF during the first 7 days, followed by reduction in NGF levels after 21 days.
, 百拇医药
Choline acetyltransferase levels remained elevated during the 21 days, indicating that "biologically active NGF is released from the synthetic microparticles at levels sufficient to affect cholinergic cell survival and/or differentiation."
"When we stopped the experiment at 21 days, the NGF was gone, but the effect on the tissue was still present, so it is not clear how the rate of protein release is related to the function of the tissue," Dr. Saltzman told Reuters Health. "We think that longer release will help. In our previous results with NGF, we have made materials that last for up to 2 months. With other proteins--antibodies, in particular--we have made polymeric systems that last for several years."
, http://www.100md.com
Drs. Mahoney and Saltzman suggest that one possible application of their technique would be to target microparticles to specific cell populations within the neo-tissue. An example would be to coat the microparticles with n-cadherin to target NGF sources to neurons.
They also recommend combining microparticles that release agents promoting distinct aspects of transplanted cell function, such as axon guidance, intracellular signaling, or immune response modification. This would make the neo-tissues specific for the treatment of neurodegenerative diseases and spinal cord injuries.
Dr. Saltzman added, "One other application where we think that this might be useful is in diabetes treatment, for which we could make neo-tissues from pancreatic cells."
Nat Biotechnol 2001;19:934-939.
-Westport Newsroom 203 319 2700, 百拇医药