The number of clinical trials using mesenchymal stem cells (MSCs) has increased since 2008, but this trend slowed in the past several years and dropped precipitously in 2018. Previous reports have analyzed MSC clinical trials by disease, phase, cell source, country of origin, and trial initiation date, all of which can be downloaded directly from ClinicalTrials.gov. We have extended analyses to a larger group of 914 MSC trials reported through 2018. To search for potential factors that may influence the design of new trials, we extracted data on routes of administration and dosing from individual ClinicalTrials.gov records as this information cannot be downloaded directly from the database. Intravenous (IV) injection is the most common, least invasive and most reproducible method, accounting for 43% of all trials. The median dose for IV delivery is 100 million MSCs/patient/dose. Analysis of all trials using IV injection that reported positive outcomes indicated minimal effective doses (MEDs) ranging from 70 to 190 million MSCs/patient/dose in 14/16 trials with the other two trials administering much higher doses of at least 900 million cells. Doseresponse data showing differential efficacy for improved outcomes were reported in only four trials, which indicated a narrower MED range of 100-150 million MSCs/ patient with lower and higher IV doses being less effective. The results suggest that it may be critical to determine MEDs in early trials before proceeding with large clinical trials.

Pancreatic cancer is one of the most aggressive malignancies, accounting for more than 45,750 deaths annually in the U.S. alone. The aggressive nature and late diagnosis of pancreatic cancer, coupled with the limitations of existing chemotherapy, present the pressing need for the development of novel therapeutic strategies. Recent reports have demonstrated a critical role of microRNAs (miRNAs) in the initiation, progression, and metastasis of cancer. Furthermore, aberrant expressions of miRNAs have often been associated with the cause and consequence of pancreatic cancer, emphasizing the possible use of miRNAs in the effective management of pancreatic cancer patients. In this review, we provide a brief overview of miRNA biogenesis and its role in fundamental cellular process and miRNA studies in pancreatic cancer patients and animal models. Subsequent sections narrate the role of miRNA in, (i) cell cycle and proliferation; (ii) apoptosis; (iii) invasions and metastasis; and (iv) various cellular signaling pathways. We also describe the role of miRNA’s in pancreatic cancer; (i) diagnosis; (ii) prognosis and (iii) therapeutic intervention. Conclusion section describes the gist of review with future directions.

Among the many molecules that contribute to glial scarring, chondroitin sulfate proteoglycans (CSPGs) are known to be potent inhibitors of neuronal regeneration. Chondroitinase ABC (ChABC), a bacterial lyase, degrades the glycosaminoglycan (GAG) side chains of CSPGs and promotes tissue regeneration. However, ChABC is thermally unstable and loses all activity within a few hours at 37 °C under dilute conditions. To overcome this limitation, the discovery of a diverse set of tailor-made random copolymers that complex and stabilize ChABC at physiological temperature is reported. The copolymer designs, which are based on chain length and composition of the copolymers, are identified using an active machine learning paradigm, which involves iterative copolymer synthesis, testing for ChABC thermostability upon copolymer complexation, Gaussian process regression modeling, and Bayesian optimization. Copolymers are synthesized by automated PET-RAFT and thermostability of ChABC is assessed by retained enzyme activity (REA) after 24 h at 37 °C. Significant improvements in REA in three iterations of active learning are demonstrated while identifying exceptionally high-performing copolymers. Most remarkably, one designed copolymer promotes residual ChABC activity near 30%, even after one week and notably outperforms other common stabilization methods for ChABC. Together, these results highlight a promising pathway toward sustained tissue regeneration.

Clinically effective modalities of treatment for spinal cord injury (SCI) still remain unsatisfactory and are largely invasive in nature. There are reports of accelerated regeneration in injured peripheral nerves by extremely low-frequency pulsed electromagnetic field (ELF-EMF) in the rat. In the present study, the effect of (50 Hz), low-intensity (17.96 μT) magnetic field (MF) exposure of rats after-hemisection of T13 spinal cord (hSCI) was investigated on sensori-motor and locomotor functions. Rats were divided into hSCI (sham-exposed) and hSCI+MF (MF: 2 h/d X 6 weeks) groups. Besides their general conditions, locomotor function by Basso, Beattie, and Brenahan (BBB) score; motor responses to noxious stimuli by threshold of tail flick (TTF), simple vocalization (TSV), tail flick latency (TFL), and neuronal excitability by H-reflex were noted. It is found that, in the hSCI+MF group, a statistically significant improvement over the hSCI control group was noted in BBB score from post-SCI wk2 and TFL and TTF by post-hSCI wk1 and wk3, respectively. Correspondingly, TSV gradually restored by post-hSCI wk5.The threshold of H-reflex was reduced on ipsilateral side vs. contralateral side in hSCI and hSCI+MF group. A complete bladder control was dramatically restored on post-hSCI day4 (vs. day7 of hSCI group) and the survival rate was 100% in the hSCI+MF group (vs. 90% of hSCI group). The results of our study suggest that extremely low-frequency (50 Hz), low-intensity (17.96 μT) MF exposure for 2 h/d x 6wks promotes recovery of sensori-motor behavior including locomotion and bladder control both in terms of temporal pattern and magnitude in hemisection injury of (T13) spinal cord rats.

Focal choroidal excavation (FCE) is defined as an area of concavity in choroid detected on optical coherence tomography. These are mostly present in macular region without evidence of accompanying scleral ectasia or posterior staphyloma. Though initially considered to be congenital, increasing number of cases have been identified in association with other choroidal pathologies such as central serous choroidopathy, choroidal neovascularisation, polypoidal choroidal vasculopathy, choroiditis, choroidal tumours. In this review article, we aim to elaborate on the morphology, pathogenesis and differential diagnosis of FCE and specifically discuss the spectrum of diseases with known association along with the impact of their treatment on FCE

Abstract-The present study was designed to investigate the effect of extremely low frequency (ELF) magnetic field (MF) on spinal cord injury (SCI)-induced osteoporosis in rats. Adult male Wistar rats (n = 24) were equally divided into sham, SCI, and SCI+MF groups. Complete transection of spinal cord (thoracic 11 vertebra) was surgically performed under anesthesia, whereas in the sham group only laminectomy was done. Post-SCI day 1, rats were either exposed (2 h/d × 8 wk) to ELF-MF (17.96 micro-Tesla, 50 Hz; SCI+MF group) or sham exposed (SCI group). Basso, Beattie, and Bresnahan (BBB) score was recorded weekly. All the rats were sacrificed 8 wk post-SCI; tibia and femur bones were isolated for the analysis of bone mineral content (BMC; total calcium [Ca], phosphorus [P], carbon [C]), bone mineral density (BMD), and biochemical status (osteocalcin, collagen I, alkaline phosphatase). The BBB score decreased post-SCI, which partially recovered after ELF-MF. In SCI rats, there was a statistically significant decrease in BMC, Ca, P, C, BMD, and biochemical level in both the bones as compared with the sham group, which was attenuated in SCI+MF rats except the C content. Electron microscopic study revealed the enhancement of microstructural composition and compactness in cortical and trabecular parts of treated bones. The results suggest that the chronic (2 h/d × 8 wk) ELF-MF exposure (17.96 micro-Tesla, 50 Hz) to SCI rats is effective in attenuating SCI-induced osteoporosis.

Pressure ulcers (PUs) or sores are a secondary complication of diabetic neuropathy and traumatic spinal cord injury (SCI). PUs tend to occur in soft tissues located around bony prominences and may heal slowly or not at all. A common mechanism underlying impaired healing of PUs may be dysfunction of the local neurovascular system including deficiency of essential neuropeptides, such as substance P (SP). Previous studies indicate that disturbance in cutaneous sensory innervation leads to a defect in all stages of wound healing, as is the case after SCI. It is hypothesized that nerve fibers enhance wound healing by promoting initial inflammation via the releasing of neuropeptides such as SP. Therefore, we investigated whether exogenous SP improves skin wound healing using in vitro and in vivo models. For in vitro studies, the effects of SP on keratinocyte proliferation and wound closure after a scratch injury were studied under normoxia (pO2 ~21%) or hypoxia (pO2 ~1%) and in presence of normal serum (10% v/v) or low serum (1% v/v) concentrations. Hypoxia and low serum both significantly slowed cell proliferation and wound closure. Under combined low serum and hypoxia, used to mimic the nutrient- and oxygen-poor environment of chronic wounds, SP (10−7 M) significantly enhanced cell proliferation and wound closure rate. For in vivo studies, two full-thickness excisional wounds were created with a 5 mm biopsy punch on the dorsum on either side of the midline of 15-week-old C57BL/6J male and female mice. Immediately, wounds were treated topically with one dose of 0.5 μg SP or PBS vehicle. The data suggest a beneficial role in wound closure and reepithelization, and thus enhanced wound healing, in male and female mice. Taken together, exogenously applied neuropeptide SP enhanced wound healing via cell proliferation and migration in vitro and in vivo. Thus, exogenous SP may be a useful strategy to explore further for treating PUs in SCI and diabetic patients.

No abstract