A microscale 3D organ on a chip for recapitulating reciprocal neuroendocrine crosstalk between the hypothalamus and the pituitary gland.

Conventional 2D or even recently developed 3Din vitroculture models for hypothalamus and pituitary gland cannot successfully recapitulate reciprocal neuroendocrine communications between these two pivotal neuroendocrine tissues known to play an essential role in controlling the body's endocrine system, survival, and reproduction. In addition, most currentvitroculture models for neuroendocrine tissues fail to properly reflect their complex multicellular structure. In this context, we developed a novel microscale chip platform, termed the 'hypothalamic-pituitary (HP) axis-on-a-chip,' which integrates various cellular components of the hypothalamus and pituitary gland with biomaterials such as collagen and hyaluronic acid. We used non-toxic blood coagulation factors (fibrinogen and thrombin) as natural cross-linking agents to increase the mechanical strength of biomaterials without showing residual toxicity to overcome drawbacks of conventional chemical cross-linking agents. Furthermore, we identified and verified SERPINB2 as a reliable neuroendocrine toxic marker, with its expression significantly increased in both hypothalamus and pituitary gland cells following exposure to various types of toxins. Next, we introduced SERPINB2-fluorescence reporter system into loaded hypothalamic cells and pituitary gland cells within each chamber of the HP axis on a chip, respectively. By incorporating this SERPINB2 detection system into the loaded hypothalamic and pituitary gland cells within our chip platform, Our HP axis-on-chip platform can better mimic reciprocal neuroendocrine crosstalk between the hypothalamus and the pituitary gland in the brain microenvironments with improved efficiency in evaluating neuroendocrine toxicities of certain drug candidates.

Homing of the Stem Cells from the Acupoint ST-36 to the Site of a Spinal Cord Injury: A Preliminary Study.

Homing of stem cells (SCs) to desired targets such as injured tissues remains a lingering problem in cell-based therapeutics. Studies on the biodistribution of intravenously administered SCs have shown the inefficacy of blood vessels as the homing path because most of the injected SCs are captured in the capillary beds of the lungs. We considered an alternative administration method using the acupuncture meridians or the primo vascular system. We injected SCs at the acupoint Zusanli (ST-36) below the knee of a nude mouse with a spinal cord injured at the thoracic T9-10 vertebrae. The SCs migrated from the ST-36, along the sciatic nerve, the lumbar 4-5, and then the spinal cord to the injury point T9-10. The SCs were not randomly scattered but were rather well aligned like marathon race runners, along the primo vascular system route toward the injury point. We observed the SCs at 1, 3, 6, 9, 12, and 15 hours after injection. The fast runners among the injected SCs took about 6 hours to reach the sciatic nerve, about 9 hours to reach the lumbar 4-5, and about 15 hours to reach the injury point T9-10.

KCHO-1, a novel herbal anti-inflammatory compound, attenuates oxidative stress in an animal model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by selective death of motor neurons in the central nervous system. The main cause of the disease remains elusive, but several mutations have been associated with the disease process. In particular, mutant superoxide dismutase 1 (SOD1) protein causes oxidative stress by activating glia cells and contributes to motor neuron degeneration. KCHO-1, a novel herbal combination compound, contains 30% ethanol and the extracts of nine herbs that have been commonly used in traditional medicine to prevent fatigue or inflammation. In this study, we investigated whether KCHO-1 administration could reduce oxidative stress in an ALS model. KCHO-1 administered to ALS model mice improved motor function and delayed disease onset. Furthermore, KCHO-1 administration reduced oxidative stress through gp91phox and the MAPK pathway in both classically activated microglia and the spinal cord of hSOD1G93A transgenic mice. The results suggest that KCHO-1 can function as an effective therapeutic agent for ALS by reducing oxidative stress.