Developmental Biology - Stem Cells|
Steps Closer to Curing Spina Bifida
Exosomes secreted by stem cells carry molecules that protect neurons and reduce spinal cord injury of spina bifida...
Researchers on the path to finding a cure for spina bifida have identified specific elements from stem cell that are key to protecting infant neurons and ultimately reduce lower-limb paralysis associated with spina bifida.
These elements are exosomes which are bubble like vesicles that transfer molecules from cell to cell. The molecule they carry is a small carbohydrate binding protein known as galectin 1.v
The team is now attempting to optimize this discovery for its neuroprotection and improve the severe mobility issues associated with spina bifida. Their research is published in the Journal of the Federation of American Societies for Experimental Biology or FASEB, and was led by Aijun Wang PhD, co-director of the UC Davis Health Surgical Bioengineering Laboratory.
Altering the Outcomes of Spina Bifida
UC Davis Health fetal surgeon and study co-author Diana Farmer first demonstrated in 2011 how prenatal surgery reduces neurological defects of spina bifida, a condition which occurs when the spinal cord doesn't properly close during development. Children with the condition can experience a mix of lifelong cognitive, urological, musculoskeletal and motor disabilities.
Farmer and Wang, her chief collaborator, later showed that prenatal surgery combined with human placenta-derived mesenchymal stromal cells (PMSCs) helped improve hind limb control in lab animals and dogs with spina bifida.
"We wanted to know the specific mechanisms of action of PMSC treatment that protects neurons. Our new results provide evidence that stem cell secretions containing exosomes expressing galectin 1.v are an important therapeutic benefit - giving us a path to optimize neuroprotective treatment."
Aijun Wang PhD, Surgical Bioengineering Laboratory, Department of Surgery, University of California, Sacramento; Department of Biomedical Engineering, University of California, Davis; Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children–Northern California, Sacramento, California, USA.
These findings could help researchers produce a cell-free treatment for spina bifida and other spinal cord injuries using stem cell by-products rather than stem cells alone. Stem cells influence the entire immune system as well as the target site, so the possibility of a cell-free treatment is highly attractive.
"Stem cell secretions can have the same or similar healing qualities, but also are a more stable and controllable product. We are excited about what we see so far and are anxious to further explore the clinical applications of this research."
Aijun Wang PhD
We have established early-gestation chorionic villus–derived placenta mesenchymal stromal cells (PMSCs) as a potential treatment for spina bifida (SB), a neural tube defect. Our preclinical studies demonstrated that PMSCs have the potential to cure hind limb paralysis in the fetal lamb model of SB via a paracrine mechanism. PMSCs exhibit neuroprotective function by increasing cell number and neurites, as shown by indirect coculture and direct addition of PMSC-conditioned media to the staurosporine-induced apoptotic human neuroblastoma cell line, SH-SY5Y. PMSC-conditioned media suppressed caspase activity in apoptotic SH-SY5Y cells, suggesting that PMSC secretome contributes to neuronal survival after injury. As a part of PMSC secretome, PMSC exosomes were isolated and extensively characterized; their addition to apoptotic SH-SY5Y cells mediated an increase in neurites, suggesting that they exhibit neuroprotective function. Proteomic and RNA sequencing analysis revealed that PMSC exosomes contain several proteins and RNAs involved in neuronal survival and development. Galectin 1 was highly expressed on the surface of PMSCs and PMSC exosomes. Preincubation of exosomes with anti-galectin 1 antibody decreased their neuroprotective effect, suggesting that PMSC exosomes likely impart their effect via binding of galectin 1 to cells. Future studies will include in-depth analyses of the role of PMSC exosomes on neuroprotection and their clinical applications.—Kumar, P., Becker, J. C., Gao, K., Carney, R. P., Lankford, L., Keller, B. A., Herout, K., Lam, K. S., Farmer, D. L., Wang, A. Neuroprotective effect of placenta-derived mesenchymal stromal cells: role of exosomes.
Priyadarsini Kumar, James C. Becker, Kewa Gao, Randy P. Carney, Lee Lankford, Benjamin A. Keller, Kyle Herout, Kit S. Lam, Diana L. Farmer, and Aijun Wang.
This work was funded by the California Institute of Regenerative Medicine, Craig H. Neilsen Foundation, Shriners Hospitals for Children, National Institutes of Health (grant numbers 5R01NS10076102, R03HD09160101), March of Dimes Foundation and UC Davis Center for Biophotonics.
More information about UC Davis Health and its Department of Surgery is at health.ucdavis.edu. More information about spina bifida and its treatment is on the UC Davis Children's Hospital website.
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Mar 19 2019 Fetal Timeline Maternal Timeline News
; Spina bifida is believed to be due to a combination of genetic and environmental factors. Not having enough folate in the diet before and during pregnancy plays a significant role. Other risk factors include certain antiseizure medications, obesity, and poorly controlled diabetes. Diagnosis may occur either before or after a child is born. Before birth if a blood test or amniocentesis finds a high level of alpha-fetoprotein (AFP), there is a higher risk of spina bifida. Ultrasound examination may also detect the problem. Medical imaging can confirm the diagnosis after birth. Spina bifida is a type of neural tube defect
. Image: Children's Hospital of Philadephia