There have been numerous attempts to develop stem cell transplantation approaches to promote the regeneration of spinal cord injury (SCI). Our multicenter team is currently planning to launch a first‐in‐human clinical study of an induced pluripotent stem cell (iPSC)‐based cell transplant intervention for subacute SCI. This trial was conducted as class I regenerative medicine protocol as provided for under Japan's Act on the Safety of Regenerative Medicine, using neural stem/progenitor cells derived from a clinical‐grade, integration‐free human “iPSC stock” generated by the Kyoto University Center for iPS Cell Research and Application. In the present article, we describe how we are preparing to initiate this clinical study, including addressing the issues of safety and tumorigenesis as well as practical problems that must be overcome to enable the development of therapeutic interventions for patients with chronic SCI. stem cells 2019;37:6–13

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2559 Background: Arctigenin, which is abundant in the seeds of Arctium lappa Linné, was found by a novel strategy to attenuate cancer cells’ tolerance to glucose deprivation (antiausterity) and showed antitumor activity in mouse xenograft models. GBS-01 is an orally administered drug and contains rich arctigenin extracted from Arctium lappa Linné, which is one of the traditional herbal medicine. This study investigated the maximum-tolerated dose of GBS-01 based on the frequency of dose-limiting toxicities (DLT) in patients with refractory advanced pancreatic cancer, which is considered as one of the hypoxic cancer. Methods: Histologically or cytologically proven advanced pancreatic adenocarcinoma patients refractory to gemcitabine were enrolled. GBS-01 was administered orally at escalating doses from 3g to 12g qd. DLT was defined as grade 4 hematological toxicities and grade 3 or 4 non-hematological toxicities during first 28 days of the treatment. Response evaluation based on RECIST criteria and progression-free survival were set as secondary endpoint for efficacy evaluation. Results: Fifteen patients (GBS-01 3g: 3 patients, 7.5g: 3 patients, 12g: 9 patients) were enrolled in this trial. All patients were refractory to S-1 as well as gemcitabine. All patients at the three dose levels did not demonstrate any sign of DLT. The main adverse events of this agent were increased γGTP, hyperglycemia, and increased total bilirubin, but all toxicities were extremely mild. Of all 15 enrolled patients, 1 patient showed a partial response and 4 patients had a stable disease. The median progression-free and overall survival time for all patients were 1.05 months and 5.68 months, respectively. Conclusions: The recommended dose of GBS-01 was 12 g qd (4 g as a extract of Arctium lappa Linné), and favorable clinical responses were obtained. A multicenter phase II trial is being planned to evaluate the efficacy and safety of this agent. Clinical trial information: 000005787.

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It is uncertain if acute lymphoblastic leukemia (ALL) cells expressing myeloid makers can respond to granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating factor (GM-CSF). We investigated the effects of G-CSF (0.01 microgram/ml) and GM-CSF (0.01 microgram/ml) on [3H]thymidine (TdR) uptake, and the cytotoxicity of 1-beta-D-arabinofuranosylcytosine (ara-C) in leukemia cells from 17 pediatric patients. ALL cells without myeloid markers did not respond to G-CSF or GM-CSF. On the other hand, these cytokines enhanced the [3H]TdR uptake and cell growth, not only of AML cells but also of ALL cells expressing myeloid antigens. However, G-CSF and GM-CSF did not always enhance the growth inhibitory effect of the cell cycle specific drug ara-C when the cells were co-cultured with the drug. There was no relationship between cell growth and the amount of [3H]TdR incorporation or the intracellular ara-CTP level. These results indicate the heterogeneous effects of G-CSF and GM-CSF on cell growth and ara-C sensitivity in childhood leukemia cells.