The Therapeutic Potential of Human Umbilical Cord Blood Transplantation for Neonatal Hypoxic-Ischemic Brain Injury and Ischemic Stroke

Human umbilical cord blood (HUCB) cells are rich source of immature stem cells, which have the potential to repair lost tissue. Intractable central nervous system (CNS) disorders are important targets for regenerative medicine, and the application of HUCB cells is being investigated in animal models of CNS disorders. Transplantation of HUCB has induced functional improvements in these animal models due to multiple therapeutic effects including neuroprotection, anti-inflammation, angiogenesis, and neurogenesis. HUCB cells are easily available and safer than other stem cells used in transplantation therapy. In this review, we focus on HUCB transplantation as an encouraging therapeutic approach for animal models of neonatal hypoxic-ischemic brain injury and ischemic stroke

Biological mechanism and clinical effect of protein-bound polysaccharide K (KRESTIN®): review of development and future perspectives

The mechanism of action of protein-bound polysaccharide K (PSK; KRESTIN®) involves the following actions: (1) recovery from immunosuppression induced by humoral factors such as transforming growth factor (TGF)-β or as a result of surgery and chemotherapy; (2) activation of antitumor immune responses including maturation of dendritic cells, correction of Th1/Th2 imbalance, and promotion of interleukin-15 production by monocytes; and (3) enhancement of the antitumor effect of chemotherapy by induction of apoptosis and inhibition of metastasis through direct actions on tumor cells. The clinical effectiveness of PSK has been demonstrated for various cancers. In patients with gastric or colorectal cancer, combined use of PSK with postoperative adjuvant chemotherapy prolongs survival, and this effect has been confirmed in multiple meta-analyses. For small-cell lung carcinoma, PSK in conjunction with chemotherapy prolongs the remission period. In addition, PSK has been shown to be effective against various other cancers, reduce the adverse effects of chemotherapy, and improve quality of life. Future studies should examine the effects of PSK under different host immune conditions and tumor properties, elucidate the mechanism of action exhibited in each situation, and identify biomarkers

Induction of regional chemokine expression in response to human umbilical cord blood cell infusion in the neonatal mouse ischemia-reperfusion brain injury model.

Regenerative medicine using umbilical cord blood (UCB) cells shows promise for the treatment of cerebral palsy. Although the efficacy of this therapy has been seen in the clinic, the mechanisms by which UCB cells interact and aid in the improvement of symptoms are not clear. We explored the chemokine expression profile in damaged brain tissue in the neonatal mouse ischemia-reperfusion (IR) brain injury model that was infused with human UCB (hUCB) cells. IR brain injury was induced in 9-day-old NOD/SCID mice. hUCB cells were administered 3 weeks post brain injury. Chemokine expression profiles in the brain extract were determined at various time points. Inflammatory chemokines such as CCL1, CCL17, and CXCL12 were transiently upregulated by 24 hours post brain injury. Upregulation of other chemokines, including CCL5, CCL9, and CXCL1 were prolonged up to 3 weeks post brain injury, but most chemokines dissipated over time. There were marked increases in levels of CCL2, CCL12, CCL20, and CX3CL1 in response to hUCB cell treatment, which might be related to the new recruitment and differentiation of neural stem cells, leading to the induction of tissue regeneration. We propose that the chemokine expression profile in the brain shifted from responding to tissue damage to inducing tissue regeneration. hUCB cell administration further enhanced the production of chemokines, and chemokine networks may play an active role in tissue regeneration in neonatal hypoxic-ischemic brain injury

Additional file 1: Figure S1. of CCL11 promotes migration and proliferation of mouse neural progenitor cells

The time-lapse movie of NPC migration. Images were captured every 15 minutes for 24 hours. (A) NPCs did not migrate toward the PBS-injected side. (B) After CCL11 injection, NPCs actively proliferated and migrated toward the CCL11-injected side. (ZIP 144651 kb

Additional file 2: Figure S2. of CCL11 promotes migration and proliferation of mouse neural progenitor cells

The immunostaining in the model mice of neonatal hypoxic-ischemic brain injury and the sham-operated mice. (A) PSA-NCAM immunostaining image of SVZ in the model mouse. Red: PSA-NCAM; blue: DAPI. Scale bar = 50 μm. (B) Number of PSA-NCAM-positive cells per slice. N = 8. The data are presented as the mean numbers of PSA-NCAM-positive cells in the injury side and the intact side ± SD. * P < 0.05. (C) Dcx immunostaining image of SVZ in the sham-operated mouse. N = 6. Green: Dcx; blue: DAPI. Scale bar = 50 μm. (D) Number of Dcx-positive cells per slice. N = 8. The data are presented as the mean numbers of Dcx-positive cells in the sham-operated side and the intact side ± SD. n.s. not significant. (PDF 655 kb