Researchers have succeeded in identifying and eliminating a substance that causes tumors, a barrier until recently to stem cell therapy.
A group of researchers at Yonsei University said that neural precursor cells differentiated from embryonic stem cells and induced pluripotent stem cells could induce mesodermal tumors in clinical applications even though remnant pluripotent cells were not detected and announced on May 6 that they have found a clue to solve the problem.
One of the biggest problems arising from cell therapy products made of stem cells in clinical applications is that they can induce tumors. So far undifferentiated cells left over after stem cells are differentiated into certain type of cells have been considered tumorigenic. Thus, researchers tried to completely eliminate the undifferentiated cells, but neural stem cell therapy without these undifferentiated cells still resulted in mesodermal tumors or other unwanted cells, including pigmented cells, raising concerns over safety.
Researchers found that polysialic acid-neural cell adhesion molecule (PSA-NCAM)-negative neural crest cells emerging during induction of neural precursor cells from pluripotent stem cells in vitro can cause mesodermal tumors. Neural crest cells can developmentally be differentiated into melanocytes, neurons and glia cells of peripheral nerve system, as well as connective tissue cells, chondrocytes, osteocytes, and adipocytes of the craniofacial complex. However, when differentiated neural cells are used for cell therapy in central nervous system, neural crest cells mixed in differentiated neural precursor cells can result in unwanted cells or mesodermal tumors.
Researchers succeeded in completely separating neural crest cells from neural cells by using antibody against PSA-NCAM. When PSA-NCAM –negative neural crest cells were transplanted into an animal brain, they could cause the formation of mesodermal tumors and unwanted grafts. However, PSA-NCAM –positive neural precursor cells did not cause unwanted cells or tumors, after being transplanted into an animal brain. Researchers also found that highly pure neural precursor cells made of separated neural cells that contain the PSA-NCAM molecule turn out to be very effective and safe when they were transplanted into animal models of strokes or spinal cord injury.
"We are preparing clinical trials with PSA-NCAM-positive pure neural cells to treat human patients who have suffered from spinal cord injury," said Yonsei University College of Medicine professor Kim Dong-Wook, who led the research.
The research results were published in Stem Cell Reports on April 30, an International Society for Stem Cell Research (ISSCR) journal.
(http://www.cell.com/stem-cell-reports/abstract/S2213-6711(15)00102-2)
By Limb Jae-un
Korea.net Staff Writer
Photo: Yonsei University
jun2@korea.kr
A group of researchers at Yonsei University said that neural precursor cells differentiated from embryonic stem cells and induced pluripotent stem cells could induce mesodermal tumors in clinical applications even though remnant pluripotent cells were not detected and announced on May 6 that they have found a clue to solve the problem.
One of the biggest problems arising from cell therapy products made of stem cells in clinical applications is that they can induce tumors. So far undifferentiated cells left over after stem cells are differentiated into certain type of cells have been considered tumorigenic. Thus, researchers tried to completely eliminate the undifferentiated cells, but neural stem cell therapy without these undifferentiated cells still resulted in mesodermal tumors or other unwanted cells, including pigmented cells, raising concerns over safety.
Yonsei University scientists have found that PSA-NCAM-positive neural precursor cells do not induce tumors or unwanted grafts while PSA-NCAM-negative neural crest cells are tumorigenic after they were transplanted into the brain of animals.
Researchers found that polysialic acid-neural cell adhesion molecule (PSA-NCAM)-negative neural crest cells emerging during induction of neural precursor cells from pluripotent stem cells in vitro can cause mesodermal tumors. Neural crest cells can developmentally be differentiated into melanocytes, neurons and glia cells of peripheral nerve system, as well as connective tissue cells, chondrocytes, osteocytes, and adipocytes of the craniofacial complex. However, when differentiated neural cells are used for cell therapy in central nervous system, neural crest cells mixed in differentiated neural precursor cells can result in unwanted cells or mesodermal tumors.
Researchers succeeded in completely separating neural crest cells from neural cells by using antibody against PSA-NCAM. When PSA-NCAM –negative neural crest cells were transplanted into an animal brain, they could cause the formation of mesodermal tumors and unwanted grafts. However, PSA-NCAM –positive neural precursor cells did not cause unwanted cells or tumors, after being transplanted into an animal brain. Researchers also found that highly pure neural precursor cells made of separated neural cells that contain the PSA-NCAM molecule turn out to be very effective and safe when they were transplanted into animal models of strokes or spinal cord injury.
"We are preparing clinical trials with PSA-NCAM-positive pure neural cells to treat human patients who have suffered from spinal cord injury," said Yonsei University College of Medicine professor Kim Dong-Wook, who led the research.
The research results were published in Stem Cell Reports on April 30, an International Society for Stem Cell Research (ISSCR) journal.
(http://www.cell.com/stem-cell-reports/abstract/S2213-6711(15)00102-2)
By Limb Jae-un
Korea.net Staff Writer
Photo: Yonsei University
jun2@korea.kr
