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Embryo-derived stem cells hold enormous potential for producing cell-based transplantation therapies, allowing high-throughput drug screening and delineating early embryonic development. However, potential clinical applications must first be tested for safety and efficacy in preclinical animal models. Due to physiological and genetic parity to humans, the domestic dog is widely used as a clinically relevant animal model for cardiovascular, neurodegenerative, orthopedic, and oncologic diseases. Therefore, we established numerous putative canine embryonic stem cell (cESC) lines by immunodissection of the inner cell mass (ICM), which we termed OVC.ID.1-23, and by explant outgrowths from whole canine blastocysts, named OVC.EX.1-16. All characterized lines were immunopositive for OCT4, SOX2, NANOG, SSEA-3, and SSEA-4; displayed high telomerase and alkaline phosphatase (ALP) activities; and were maintained in this state up to 37 passages ( approximately 160 days). Colonies from OVC.EX lines showed classic domed hESC-like morphology surrounded by a ring of fibroblast-like cells, whereas all OVC.ID lines exhibited a mixed cell colony of tightly packed cESCs surrounded by a GATA6+/CDX2- hypoblast-derived support layer. Spontaneous serum-only differentiation without feeder layers demonstrated a strong lineage selection associated with the colony niche type, and not the isolation method. Upon differentiation, cESC lines formed embryoid bodies (EB) comprised of cells representative of all germinal layers, and differentiated into cell types of each layer. Canine ESC lines such as these have the potential to identify differences between embryonic stem cell line derivations, and to develop or to test cell-based transplantation therapies in the dog before attempting human clinical trials.

OBJECTIVE Multiple meningiomas account for 1%-10% of meningiomas. This study describes epidemiological aspects of the disease and its management, which is more challenging than for single tumors. METHODS A consecutive series of adult patients with ≥ 2 spatially separated meningiomas was reviewed. Patients with neurofibromatosis Type 2 were excluded. The authors collected clinical, imaging, histological, and treatment data to obtain information on epidemiology, management options, and outcomes of active treatment and surveillance. RESULTS A total of 133 consecutive patients were included over 25 years, with a total of 395 synchronous and 53 metachronous meningiomas, and a median of 2 tumors per patient. One hundred six patients had sporadic disease, 26 had radiation-induced disease, and 1 had familial meningiomatosis. At presentation, half of the patients were asymptomatic. In terms of their maximum cross-sectional diameter, the tumors were small (≤ 2 cm) in 67% and large (> 4 cm) in 11% of the meningiomas. Fifty-four patients had upfront treatment, and 31 had delayed treatment after an observation period (mean 4 years). One in 4 patients had ≥ 2 meningiomas treated. Overall, 64% of patients had treatment for 142 tumors-67 with surgery and 18 with radiotherapy alone. The mean follow-up was 7 years, with 13% of treated patients receiving salvage therapy. Approximately 1 in 4 patients who underwent surgery had ≥ 1 WHO Grade II or III meningioma. Meningiomas of different histological subtypes and grades in the same patient were not uncommon. CONCLUSIONS Multiple meningiomas are often asymptomatic, probably because the majority are small and a significant proportion are induced by radiation. Approximately two-thirds of patients with multiple meningiomas require therapy, but only one-third of all meningiomas need active treatment. The authors recommend surveillance for stable and asymptomatic meningiomas and therapy for those that are symptomatic or growing.

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Spinal cord injury has a significant societal and personal impact. Although the majority of injuries involve the cervical spinal cord, few studies of cell transplantation have used clinically relevant models of cervical spinal cord injury, limiting translation into clinical trials. Given this knowledge gap, we sought to examine the effects of neural stem/precursor cell (NPC) transplants in a rodent model of bilateral cervical contusion-compression spinal cord injury. Bilateral C6-level clip contusion-compression injuries were performed in rats, which were then blindly randomized at 2 weeks after injury into groups receiving adult brain-derived NPCs, vehicle, or sham operation. Long-term survival of NPCs was evident at 10 weeks after transplant. Cell grafts were localized rostrocaudally surrounding the lesion, throughout white and gray matter. Graft-derived cells were found within regions of gliotic scar and motor tracts and deposited myelin around endogenous axons. The majority of NPCs developed an oligodendroglial phenotype with greater neuronal profiles in rostral grafts. Following NPC transplantation, white matter was significantly increased compared with control. Astrogliosis and glial scar deposition, measured by GFAP-positive and chondroitin sulfate proteoglycan-positive volume, was significantly reduced. Forelimb grip strength, fine motor control during locomotion, and axonal conduction (by in vivo electrophysiology) was greater in cell-treated animals compared with vehicle controls. Transplantation of NPCs in the bilaterally injured cervical spinal cord results in significantly improved spinal cord tissue and forelimb function, warranting further study in preclinical cervical models to improve this treatment paradigm for clinical translation.