Olfactory Stem Cells

Unmet Medical/Market Requirements

Currently, acute stroke is the third of the top ten causes of death in Taiwan. According to statistics of Ministry of Health and Welfare, 48 out of 100,000 people died from cerebrovascular diseases in 2015. Stroke is mainly due to vascular thrombosis, sclerosis or blocking that occurs in different parts of the brain, resulting in losses of nerve functions with varying degrees, such as sudden limb hemiplegia, aphasia or numbness of hands and feet. The current treatment methods are

(I) Antiplatelet therapy and (II) Thrombolytic therapy. However, the former must be provided within 48 hours in the initial stage of ischemic stroke, and attention must be paid to whether patients have a history of upper gastrointestinal ulcer or bleeding. The latter is to be provided within 3 hours since the occurrence of ischemic stroke; attention must be paid to whether it results in cerebral hemorrhage or hemorrhage in the other parts of the body, and whether it is threatening to the life of patients. Therefore, currently there is only the initial first-aid treatment strategy, but no effective way for treatment of ischemic stroke. Stroke causes ischemic death in brain neural cells, and neural cells are unable to regenerate after their death. Therefore, U-NEURON BIOMEDICAL has put forward an effective treatment strategy by autologous olfactory stem cells (OSCs) to repair brain neural cells damaged by ischemia and to improve the nerve function loss and the quality of life of stroke patients.質。

Project Objectives and Research Areas

OSCs are cells in the form of neuroglial cells that exist in in the olfactory system (Su and He, 2010); such cells can guide axon growth. It grows from neurons in the nasal mucosa to the brain olfactory bulb and forms synapses. Therefore, OSCs have been found to have the ability to help nerves regenerate, and are applied to the treatment of spinal cord injury (Kato, et al., 2000) and

animal models of Parkinson’s disease (Agrawal, et al., 2004). In addition, OSCs not only have the ability of neural differentiation, but also secrete neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF) and glial cell line-derived neurotrophic factor (GDNF). These growth factors all contribute to neuronal plasticity and increased functional recovery in animal models of stroke (Chen, et al., 2005).

Research Team and Expertise

U-NEURON BIOMEDICAL’s technology comes from the technical team led by Woei-Cheang Shyu, physician of China Medical University Hospital, Taichung. In the past decade or so, the technology has been developed by using olfactory stem cells for treatment of ischemic stroke. Fairly good results have been achieved in the treatment of ischemic stroke in animals, and the results have been published in the international Journal of Clinical Investigation (Shyu, et al., 2008). To transfer this technology to clinical autologous transplantation for the treatment for cerebral stroke, Phase I clinical trial started in 2012, and ended at the end of 2015. Six subjects with old cerebral stroke (at least from 6 months to 5 years) of adult patients (35 to 70 years old) participated in this trial, and these six subjects have no adverse reactions to olfactory stem cells from autologous transplantation, which can confirm that the technology in using autologous olfactory stem cells for treatment of ischemic stroke is quite safe.

Therefore, in order to further expand and verify the safety of this technology and the effectiveness of the treatment for old cerebral stroke, U-NEURON BIOMEDICAL plans to start Phase I/II clinical trials in the initial stage and has started to build core treatment facilities to produce GMP cells required for Phase III clinical trials with the precondition of conforming to PIC/S Regulation

References
Agrawal AK, Shukla S, Chaturvedi RK, Seth K, Srivastava N, Ahmad A, Seth PK. 2004. Olfactory ensheathing cell transplantation restores functional deficits in rat model of Parkinson's disease: a cotransplantation approach with fetal ventral mesencephalic cells. Neurobiol Dis 16: 516-526. Chen J, Zhang C, Jiang H, Li Y, Zhang L, Robin A, Katakowski M, Lu M, Chopp M. 2005. Atorvastatin induction of VEGF a nd BDNF promotes brain plasticity after stroke in mice. J Cereb Blood Flow Metab 25: 281-290. Kato T, Honmou O, Uede T, Hashi K, Kocsis JD. 2000. Transplantation of human olfactory ensheathing cells elicits remyelination of demyelinated rat spinal cord. Glia 30: 209-218.Shyu WC, Liu DD, Lin SZ, Li WW, Su CY, Chang YC, Wang HJ, Wang HW, Tsai CH, Li H. 2008. Implantation of olfactory ensheathing cells promotes neuroplasticity in murinemodels of stroke. J Clin Invest 118: 2482- 2495. Su Z, He C. 2010. Olfactory ensheathing cells: biology in neural development and regeneration. Prog Neurobiol 92: 517-532.

Technical Summary

Patents and Certificates

U-NEURON BIOMEDICAL is devoted to the development of stem cell isolation, storage and clinical applications. It owns the Patent on the Technology of Isolation and Culture of Amniotic Fluid Stem Cell, and has signed a service contract on the support of cell operation laboratory facilities and instruments with Bioresource Collection and Research Center; meanwhile, it has completed the pre-clinical trial for treatment of urinary incontinence with amniotic fluid stem cells with National Yang-Ming University. Recently, U-NEURON BIOMEDICAL has cooperated with Linkou Chang Gung Memorial Hospital on clinical trials of a rare disease – osteogenesis imperfecta (glass doll), and continues the research and development of the latest cell treatment and applications.

Through continuous research, U-NEURON BIOMEDICAL carries out manufacturing that meets clinical specifications, creates new stem cell therapy technologies to fill current medical gaps, and popularizes stem cell technology and cell therapy products through professional technology development and medical research, creating real value of regenerative medicine and a better life for humankind.。

 嗅幹細胞

 嗅幹細胞是具有神經膠質細胞形態的細胞存在嗅覺系統中(Su and He, 2010),此細胞可引導軸突生長,從鼻腔黏膜層的

神經元往大腦嗅球生長並形成突觸。因此,OSCs被發現具有幫助神經再生的能力,並應用在治療脊髓損傷(Kato, et al., 2000)

和巴金森氏病的動物模型(Agrawal, et al., 2004)。此外,OSCs不但具有神經分化的能力,其自身更會分泌

神經營養因子(neurotrophic factors),如大腦衍生神經滋養因子(brain-derived neurotrophic factor (BDNF))、

血管內皮生長因子(vascular endothelial growth factor (VEGF))和膠質細胞源性神經營養因子

(glial cell line–derived neurotrophic factor (GDNF)),這些生長因子都有助於促進神經可塑性

(neuronal plasticity)及增加功能恢復在腦中風的動物模型中(Chen, et al., 2005)。