This article addresses the stability of chondrogenic phenotype and the transdifferentiation potential of bone marrow–derived mesenchymal stem cells (MSCs) at distinct stages of differentiation. Differentiated MSCs were expected to maintain cartilage-like gene expression pattern in the absence of any chondrogenic growth factor or in the presence of osteogenic signals. MSCs encapsulated in alginate beads were treated with transforming growth factor (TGF)-β3 for 3, 6, or 14 days and then cultured in absence of TGF-β for the remainder of the 2-week culture period. Additionally, cells were cultured in osteogenic medium after TGF-β-mediated chondroinduction. Gene expression of col2a1, aggrecan, COMP, alkaline phosphatase (AP), and correlating protein synthesis was analyzed. After short-term stimulation with TGF-β, MSCs maintained a chondrogenic phenotype. Chondrogenic gene expression and protein synthesis directly correlated with the extent of stimulation time and the concentration of TGF-β. Pretreatment with TGF-β could prevent AP mRNA expression of encapsulated MSCs. TGF- β stimulation within the first 3 days of culture seems to be crucial for the expression of a chondrogenic phenotype. Fully differentiated and encapsulated MSCs are not able to transdifferentiate into osteoblasts. These findings give rise to a better understanding of the behavior of cartilage grafts affected by local factors of osteochondral transplantation sites in vivo.

Cell transplantation, as a therapeutic intervention for spinal cord injury (SCI), has been extensively studied by researchers in recent years. A number of different kinds of stem cells, neural progenitors, and glial cells have been tested in basic research, and most have been excluded from clinical studies because of a variety of reasons, including safety and efficacy. The signaling pathways, protein interactions, cellular behavior, and the differentiated fates of experimental cells have been studiedin vitroin detail. Furthermore, the survival, proliferation, differentiation, and effects on promoting functional recovery of transplanted cells have also been examined in different animal SCI models. However, despite significant progress, a “bench to bedside” gap still exists. In this paper, we comprehensively cover publications in the field from the last years. The most commonly utilized cell lineages were covered in this paper and specific areas covered include survival of grafted cells, axonal regeneration and remyelination, sensory and motor functional recovery, and electrophysiological improvements. Finally we also review the literature on thein vivotracking techniques for transplanted cells.

The molecular mechanisms underlying the differentiation of neural progenitor cells (NPCs) remain poorly understood. In this study we investigated the role of Ca2+ and cAMP (cyclic adenosine monophosphate) in the differentiation of NPCs extracted from the subventricular zone of E14.5 rat embryos. Patch clamp recordings revealed that increasing cAMP-signaling with Forskolin or IBMX (3-isobutyl-1-methylxantine) significantly facilitated neuronal functional maturation. A continuous application of IBMX to the differentiation medium substantially increased the functional expression of voltage-gated Na+ and K+ channels, as well as neuronal firing frequency. Furthermore, we observed an increase in the frequency of spontaneous synaptic currents and in the amplitude of evoked glutamatergic and GABAergic synaptic currents. The most prominent acute effect of applying IBMX was an increase in L-type Ca2+currents. Conversely, blocking L-type channels strongly inhibited dendritic outgrowth and synapse formation even in the presence of IBMX, indicating that voltage-gated Ca2+ influx plays a major role in neuronal differentiation. Finally, we found that nifedipine completely blocks IBMX-induced CREB phosphorylation (cAMP-response-element-binding protein), indicating that the activity of this important transcription factor equally depends on both enhanced cAMP and voltage-gated Ca2+-signaling. Taken together, these data indicate that the up-regulation of voltage-gated L-type Ca2+-channels and early electrical excitability are critical steps in the cAMP-dependent differentiation of SVZ-derived NPCs into functional neurons. To our knowledge, this is the first demonstration of the acute effects of cAMP on voltage-gated Ca+2channels in NPC-derived developing neurons.

Objective Chronic neuropathic pain in the groin is a severe condition and difficult to treat. Dorsal root ganglion stimulation (DRGS) covers discrete painful areas precisely with its stimulation power in comparison to spinal cord stimulation (SCS). It was our hypothesis that DRGS provides a long-term relief of chronic groin pain over a period of more than three years. Materials and Methods Patients (age >18 years) with chronic neuropathic groin pain were prospectively examined. After a successful test-trial (duration of 3–10 days, pain decrease >50%) a permanent generator was implanted. The patients were re-examined after three months, then after one year, two, and three years. We used the Visual Analogue Scale (VAS), the Pain Disability Index (PDI), the Pain Catastrophizing Scale (PCS), the Brief Pain Inventory (BPI), and the Beck Depression Inventory (BDI) for the assessment. Results We included 34 consecutive patients (13 female, 21 male, mean age 50.4 years, range of age 24–84 years, 30/34 trial to permanent conversion) during the time period from 2012 until 2016. Thirty patients had a successful test-trial and a generator was subsequently implanted. Results after three years: the preoperative VAS dropped from Mdn = 8 to Mdn = 4.5 (p = 0.001). The PDI decreased from Mdn = 48 to Mdn = 23 (p = 0.004). The PCS changed from Mdn = 31 to Mdn = 16 (p = 0.006). The BPI dropped from Mdn = 76 to Mdn = 30 (p = 0.003). The BDI decreased from Mdn = 17 to Mdn = 7 (p = 0.010). Five patients showed complications (16.7%). Conclusion In this study, DRGS proved an efficient long-term method for the treatment of chronic neuropathic groin pain and we strongly recommend its use.

Cerebral hemiatrophy or Dyke-Davidoff-Masson syndrome is a condition characterized by seizures, facial asymmetry, contralateral hemiplegia or hemiparesis, and mental retardation. These findings are due to cerebral injury that may occur early in life or in utero. The radiological features are unilateral loss of cerebral volume and associated compensatory bone alterations in the calvarium, like thickening, hyperpneumatization of the paranasal sinuses and mastoid cells and elevation of the petrous ridge. The authors describe three cases. Classical findings of the syndrome are present in variable degrees according to the extent of the brain injury. Pathogenesis is commented.