Fumiya Kano

Secreted Ectodomain of Sialic Acid-Binding Ig-Like Lectin-9 and Monocyte Chemoattractant Protein-1 Promote Recovery after Rat Spinal Cord Injury by Altering Macrophage Polarity

Engrafted mesenchymal stem cells from human deciduous dental pulp (SHEDs) support recovery from neural insults via paracrine mechanisms that are poorly understood. Here we show that the conditioned serum-free medium (CM) from SHEDs, administered intrathecally into rat injured spinal cord during the acute postinjury period, caused remarkable functional recovery. The ability of SHED-CM to induce recovery was associated with an immunoregulatory activity that induced anti-inflammatory M2-like macrophages. Secretome analysis of the SHED-CM revealed a previously unrecognized set of inducers for anti-inflammatory M2-like macrophages: monocyte chemoattractant protein-1 (MCP-1) and the secreted ectodomain of sialic acid-binding Ig-like lectin-9 (ED-Siglec-9). Depleting MCP-1 and ED-Siglec-9 from the SHED-CM prominently reduced its ability to induce M2-like macrophages and to promote functional recovery after spinal cord injury (SCI). The combination of MCP-1 and ED-Siglec-9 synergistically promoted the M2-like differentiation of bone marrow-derived macrophages in vitro, and this effect was abolished by a selective antagonist for CC chemokine receptor 2 (CCR2) or by the genetic knock-out of CCR2. Furthermore, MCP-1 and ED-Siglec-9 administration into the injured spinal cord induced M2-like macrophages and led to a marked recovery of hindlimb locomotor function after SCI. The inhibition of this M2 induction through the inactivation of CCR2 function abolished the therapeutic effects of both SHED-CM and MCP-1/ED-Siglec-9. Macrophages activated by MCP-1 and ED-Siglec-9 extended neurite and suppressed apoptosis of primary cerebellar granule neurons against the neurotoxic effects of chondroitin sulfate proteoglycans. Our data suggest that the unique combination of MCP-1 and ED-Siglec-9 repairs the SCI through anti-inflammatory M2-like macrophage induction.

Multifaceted Neuro-Regenerative Activities of Human Dental Pulp Stem Cells for Functional Recovery after Spinal Cord Injury

Spinal cord injury (SCI) often leads to persistent functional deficits due to the loss of neurons and glia and to limited axonal regeneration after such injury. Recently, three independent groups have reported marked recovery of hindlimb locomotor function after the transplantation of human adult dental pulp stem cells (DPSCs) and stem cells from human exfoliated deciduous teeth (SHEDs) into rats or mice with acute, sub-acute or chronic SCI. This review summarizes the primary characteristics of human dental pulp stem cells and their therapeutic benefits for treating SCI. Experimental data from multiple preclinical studies suggest that pulp stem cells may promote functional recovery after SCI through multifaceted neuro-regenerative activities.

Analysis of the Neuroregenerative Activities of Mesenchymal Stem Cells in Functional Recovery after Rat Spinal Cord Injury

Spinal cord injury (SCI) involves concurrent, interacting pathological processes, and requires a multifaceted therapeutic strategy. Stem cell-based transplantation holds great promise as such an approach. We have reported that stem cells derived from human dental pulp have remarkable neuroregenerative activity, and that when transplanted into animal models of SCI, these cells promote functional recovery by inhibiting massive SCI-induced apoptosis, preserving neural fibers and myelin, regenerating transected axons, and replacing damaged cells by differentiating into oligodendrocytes. Here, we introduce some details of our experimental procedures, which may serve as a guide for designing experiments to evaluate the therapeutic benefits of various types of stem cells.

Secreted Ectodomain of Sialic Acid‐Binding Ig‐Like Lectin‐9 and Monocyte Chemoattractant Protein‐1 Synergistically Regenerate Transected Rat Peripheral Nerves by Altering Macrophage Polarity

Peripheral nerves (PNs) exhibit remarkable self‐repairing reparative activity after a simple crush or cut injury. However, the neuronal transection involving a nerve gap overwhelms their repairing activity and causes persistent paralysis. Here, we show that an implantation of the serum‐free conditioned medium from stem cells from human exfoliated deciduous teeth (SHED‐CM) immersed in a collagen sponge into the nerve gap formed by rat facial nerves transection restored the neurological function. In contrast, SHED‐CM specifically depleted of a set of anti‐inflammatory M2 macrophage inducers, monocyte chemoattractant protein‐1 (MCP‐1) and the secreted ectodomain of sialic acid‐binding Ig‐like lectin‐9 (sSiglec‐9) lost the ability to restore neurological function in this model. Notably, the combination of MCP‐1 and sSiglec‐9 induced the polarization of M2 macrophages in vitro, resulting in the expression of multiple trophic factors that enhanced proliferation, migration, and differentiation of Schwann cells, blood vessel formation, and nerve fiber extension. Furthermore, the implantation of a collagen graft containing MCP‐1/sSiglec‐9 into the nerve gap induced anti‐inflammatory M2 macrophage polarization, generated a Schwann‐cell bridge instead of fibrotic scar, induced axonal regrowth, and restored nerve function. The specific elimination of M2 macrophages by Mannosylated‐Clodrosome suppressed the MCP‐1/sSiglec‐9‐mediated neurological recovery. Taken together, our data suggest that MCP‐1/sSiglec‐9 regenerates PNs by inducing tissue‐repairing M2 macrophages and may provide therapeutic benefits for severe peripheral nerve injuries. Stem Cells 2017;35:641–653

Nasal hemangiopericytoma successfully treated with a combination of rIL-2 and extranasal approaches

Abstract Hemangiopericytomas (HPCs) are uncommon vascular tumors originating from extracapillary cells called pericytes, and rarely occur in the nose or paranasal sinuses. We treated a 57-year-old man with nasal HPC who presented with nasal obstruction and hemorrhage. Nasal endoscopy showed a readily bleeding mass between the right nasal septum and inferior turbinate. Enhanced CT revealed a heterogeneous mass lesion with an enhancement effect that filled the right nasal cavity. A biopsy specimen was proved to exhibit a HPC histopathology. Recombinant interleukin-2 (rIL-2) was administered with a measurement of natural killer cell (NK cell) activity. Afterwards, wide excision with an extranasal approach was performed. The use of rIL-2 caused not only increased NK cell activity but also a reduction in the tumor size. With a combination of rIL-2 and wide excision with extranasal approaches, no local recurrence or metastasis has occurred over the last 4 years.

Adult retropharyngeal abscess

A 60-year-old man was referred to our hospital after complaining of throat pain for several days. He described the condition as a cold with sore throat. A physical examination revealed swelling of the posterior wall of the oropharynx. Sagittal computed tomography revealed a 3 × 1 cm abscess with ring enhancement in the retropharyngeal space (Fig. 1). Therefore, he was diagnosed with a retropharyngeal abscess

Efficacy of the red blood cell distribution width for predicting the prognosis of Bell palsy: a pilot study

The aim of this study was to investigate the association between RDW values and the prognosis of patients with Bell palsy in an effort to find a prognostic biomarker that predicts recovery from Bell palsy. We measured RDW and evaluated facial movement in 61 patients with Bell palsy aged 50 years and less. All patients were treated with a steroid plus an antiviral agent. Seven patients underwent surgery for facial nerve decompression. During the post-treatment period, patients with a Yanagihara grading score of 36 or more were regarded as having a satisfactory recovery. Patients were divided into two groups (recovered and unrecovered) according to their response to treatment, and several parameters, including the RDW, were measured for further analysis. RDW values were significantly higher in the unrecovered group than in the recovered group (13.5 ± 1.7 vs. 12.7 ± 0.7%, p = 0.046). In the multiple logistic regression model, RDW was the only factor associated with recovery from Bell palsy (odds ratio 1.93, 95% confidence interval 1.02–4.65, p = 0.042). Our preliminary study provides the first evidence that the red cell distribution width (RDW) can predict recovery from Bell palsy in patients aged 50 years and less. Further studies are necessary to elucidate the potential pathophysiological mechanisms for our findings.