Five studies from the current special issue of Cell Transplantation 24(4) devoted to work presented at the 21st meeting of the American Society for Neural Therapy and Repair (ASNTR) in 2014, a society for scientists focused on understanding the causes of, and developing cell and gene therapy and biopharmaceuticals for neurological injury and disease, are currently freely available on-line.*
MSCs promote improvement in patient with complete spinal cord injury
Complete spinal cord injury (SCI) leads to profound disability and, with long-term complications, even death. This study demonstrated the potential of transplanted bone marrow nucleated cells (BMNCs) to restore feeling and function to the lower body. Over a two year period, researchers assessed the safety and efficacy of combined intravenous/intrathecally administered autologous (self-donated) BMNCs and multiple lumbar puncture administered mesenchymal stem cell (MSC) injections in treating a patient with complete SCI. Results suggested that the treatment had the potential to produce "clinically meaningful improvements for SCI patients" as this patient experienced a restored ability to control his body trunk, a restoration of bladder and anal sensation, and gained the ability to stand with a standing frame and walk with the support of hip and knee ortheses.
Citation: Jarocha, D.; Milczarek, O.; Wedrychowicz, A.; Kwiatkowski, S.; Majka, M. Continuous Improvement After Multiple Mesenchymal Stem Cell Transplantations in a Patient With Complete Spinal Cord Injury. Cell Transplant. 24(4):661-672; 2015.
Bone marrow MSC culture enhances human neural stem cells
"Rapid loss of stemness capacity in purified prototype neural stem cells (NSCs) remains a serious challenge to basic and clinical studies aimed at repairing the central nervous system," wrote a team of researchers from the Harvard Medical School and the Boston Veteran's Administration Health System. The researchers tested human NSCs and human MSCs to find out if bone marrow-derived MSCs could enhance the "stemness" of human NSCs. They speculated that the a biological pathway called Notch-1 might be a major mechanism through which hNSCs and hMSCs communicate to 'modulate' their stemness biology through direct interactions, offering a potential strategy for hNSC stemness enhancement. After their experiments in co-culturing hNSCs and hMSCs they found that enhancement of the stemness of hNSCs occurred through Notch-1 signaling. "Our finding provides mechanistic leads for devising effective regimens to sustain and augment stemness of in vitro established hNSC and hMSC lines for use in basic science as well as translational and clinical applications," concluded the researchers.
Citation: : Haragopal, H.; Yu, D.; Zeng, X.; Kim, S-W.; Han, I-B.; Ropper, A. E.; Anderson, J. E.; Teng, Y. D. Stemness Enhancement of Human Neural Stem Cells Following Bone Marrow MSC Coculture. Cell Transplant. 24(4):645-659; 2015.
Primate model of Parkinson's disease study shows role for upgrading endogenous neurons
The possibilities for having the brain help heal itself when afflicted by neurological disorders such as Parkinson's disease (PD) is an area of interest. In this study, researchers observed primates modeled with PD and assessed changes in the numbers of neurons expressing the enzyme tyrosine hydroxylase (TH), a precursor for dopamine. They discovered "a close relationship" between PD symptom severity and striatal DA neuron numbers. The possibility of increasing the numbers of these neurons as compensation for their depletion in PD by artificial means "could prove beneficial for PD treatment, especially for individuals in the early disease stages," they concluded.
Citation: Bubak, A. N.; Redmond, D. E.; Elsworth, J. D.; Roth, R. H.; Collier, T. J.; Bjugstad, K. B.; Blanchard, B. C.; Sladek, J. R. A Potential Compensatory Role for Endogenous Striatal Tyrosine Hydroxylase-Positive Neurons in a Nonhuman Primate Model of Parkinson's Disease. Cell Transplant. 24(4):673-680; 2015.
Human pluripotent stem cells hold promise for Parkinson's disease
Recent studies have shown that human pluripotent stem cells (PSCs) may hold promise for treating Parkinson's disease (PD). Transplanted fetal neural tissue has been shown to provide improvements in PD, but the source of this tissue is limited and controversial. Looking for alternatives and proof of concept, the researchers studied the benefits of using human pluripotent stem cells (hPSCs) and neural stem cells (NSCs) to engraft into animal models of PD. "In this study we showed for the first time the successful engraftment and safety of NSCs derived from human parthenogenetic stem cells following transplantation in rodent and non-human primate PD models," concluded the researchers. "In both models, transplantation of hpNSCs led to improvement of DA (dopamine) levels, which could be explained by the multimodal actions of the NSCs, to include neuroprotection and cell replacement."
Citation: Gonzalez, R.; Garitaonandia, I.; Crain, A.; Poustovoitov, M.; Abramihina, T.; Noskov, A.; Jiang, C.; Morey, R.; Laurent, L. C.; Elsworth, J. D.; Snyder, E. Y.; Redmond, D. E.; Semechkin, R. Proof of Concept Studies Exploring the Safety and Functional Activity of Human Parthenogenetic-Derived Neural Stem Cells for the Treatment of Parkinson's Disease. Cell Transplant. 24(4):681-690; 2015.
Anti-tumor effect of secreted factors studied for effect on glioblastoma-like cells
Researchers studied the possible anti-tumor effects of the secreted factors from MSCs on four glioblastoma stem-like cells (GSLCs) and found that MSCs "have an intrinsic ability to inhibit the cell cycle, induce senescence (halt cell division) and prevent differentiation of GSLCs." "Glioblastoma multiform (GBM) is the most malignant type of brain tumor that is still incurable, due to its characteristic highly infiltrative growth and resistance to therapy," said the researchers. "The highly tumorigenic subpopulation of cells with stem cell-like properties are presumably the cause for GBM recurrence." The researchers hypothesized that the secreted factors from the MSCs could cause an alteration in the GLSCs' behavior and did in fact observe that they cause cell cycle arrest. They also found that the MSCs also increased the sensitivity of GSLCs to chemotherapy.
"At the 22nd annual meeting of the ASNTR, we are pleased to announce the publication of studies on a myriad of topics ranging from neurotrauma to developmental neurobiology to neurodegenerative conditions in Cell Transplantation," said Dr. Paul Sanberg, Senior Vice President of Research and Innovation at the University of South Florida and co-founder of the ASNTR. "We are pleased to host another conference devoted to excellence in neural research and therapy."
Citation: Kološa, K.; Motaln, H.; Herold-Mende, C.; Koršič, M.; Lah, T. T. Paracrine Effects of Mesenchymal Stem Cells Induce Senescence and Differentiation of Glioblastoma Stem-Like Cells. Cell Transplant. 24(4):631-644; 2015.