Kalliopi Alpantaki

Sympathetic and sensory neural elements in the tendon of the long head of the biceps.

BACKGROUNDnAlthough the tendon of the long head of the biceps is a well-known source of shoulder pain, the pathophysiological basis of this pain has yet to be explained. The aim of this study was to detect and characterize any nervous element of the tendon and to determine a possible explanation for pain originating from this structure.nnnMETHODSnThe nature of the neuronal innervation of the tendon of the long head of the biceps was studied immunohistochemically, in four tendons from different human cadavers, with use of neurofilament antibody 2H3, neurofilament-like antibody 3A10, calcitonin gene-related peptide, substance P, and tyrosine hydroxylase.nnnRESULTSnA large neuronal network, asymmetrically distributed along the length of the tendon with a higher degree of innervation at the tendon origin, was identified by the neurofilament and neurofilament-like antibodies 2H3 and 3A10. This innervation was found to be positive for calcitonin gene-related peptide and substance P, suggesting the presence of thinly myelinated or unmyelinated sensory neurons. It was also positive for tyrosine hydroxylase, suggesting a post-ganglionic sympathetic origin.nnnCONCLUSIONS AND CLINICAL RELEVANCEnThese findings demonstrate that the tendon of the long head of the biceps is innervated by a network of sensory sympathetic fibers, which may play a role in the pathogenesis of shoulder pain.

Thoracolumbar burst fractures: a systematic review of management.

The management of thoracolumbar burst fractures remains challenging. Ideally, it should effectively correct the deformity, induce neurological recovery, allow early mobilization and return to work, and be associated with minimal risk of complication. This article reviews the related studies reporting their clinical data for the management of thoracolumbar burst fractures, discusses the most suitable approach in cases such as these, highlights specific treatment recommendations, and proposes a treatment algorithm. Using PubMed and Scopus databases to search the term thoracolumbar burst fractures, abstracts and original articles in English investigating the treatment of thoracolumbar burst fractures were searched and analyzed.

Study of the Quantitative, Functional, Cytogenetic, and Immunoregulatory Properties of Bone Marrow Mesenchymal Stem Cells in Patients with B-Cell Chronic Lymphocytic Leukemia

The bone marrow (BM) microenvironment has clearly been implicated in the pathogenesis of B-cell chronic lymphocytic leukemia (B-CLL). However, the potential involvement of BM stromal progenitors, the mesenchymal stem cells (MSCs), in the pathophysiology of the disease has not been extensively investigated. We expanded in vitro BM-MSCs from B-CLL patients (n=11) and healthy individuals (n=16) and comparatively assessed their reserves, proliferative potential, differentiation capacity, and immunoregulatory effects on T- and B-cells. We also evaluated the anti-apoptotic effect of patient-derived MSCs on leukemic cells and studied their cytogenetic characteristics in comparison to BM hematopoietic cells. B-CLL-derived BM MSCs exhibit a similar phenotype, differentiation potential, and ability to suppress T-cell proliferative responses as compared with MSCs from normal controls. Furthermore, they do not carry the cytogenetic abnormalities of the leukemic clone, and they exert a similar anti-apoptotic effect on leukemic cells and healthy donor-derived B-cells, as their normal counterparts. On the other hand, MSCs from B-CLL patients significantly promote normal B-cell proliferation and IgG production, in contrast to healthy-donor-derived MSCs. Furthermore, they have impaired reserves, defective cellular growth due to increased apoptotic cell death and exhibit aberrant production of stromal cell-derived factor 1, B-cell activating factor, a proliferation inducing ligand, and transforming growth factor β1, cytokines that are crucial for the survival/nourishing of the leukemic cells. We conclude that ex vivo expanded B-CLL-derived MSCs harbor intrinsic qualitative and quantitative abnormalities that may be implicated in disease development and/or progression.

Herpes virus infection can cause intervertebral disc degeneration: A CAUSAL RELATIONSHIP?

It has been proposed that intervertebral disc degeneration might be caused by low-grade infection. The purpose of the present study was to assess the incidence of herpes viruses in intervertebral disc specimens from patients with lumbar disc herniation. A polymerase chain reaction based assay was applied to screen for the DNA of eight different herpes viruses in 16 patients and two controls. DNA of at least one herpes virus was detected in 13 specimens (81.25%). Herpes Simplex Virus type-1 (HSV-1) was the most frequently detected virus (56.25%), followed by Cytomegalovirus (CMV) (37.5%). In two patients, co-infection by both HSV-1 and CMV was detected. All samples, including the control specimens, were negative for Herpes Simplex Virus type-2, Varicella Zoster Virus, Epstein Barr Virus, Human Herpes Viruses 6, 7 and 8. The absence of an acute infection was confirmed both at the serological and mRNA level. To our knowledge this is the first unequivocal evidence of the presence of herpes virus DNA in intervertebral disc specimens of patients with lumbar disc herniation suggesting the potential role of herpes viruses as a contributing factor to the pathogenesis of degenerative disc disease.

Differential expression of cell cycle and WNT pathway-related genes accounts for differences in the growth and differentiation potential of Wharton’s jelly and bone marrow-derived mesenchymal stem cells

BackgroundIn view of the current interest in exploring the clinical use of mesenchymal stem cells (MSCs) from different sources, we performed a side-by-side comparison of the biological properties of MSCs isolated from the Wharton’s jelly (WJ), the most abundant MSC source in umbilical cord, with bone marrow (BM)-MSCs, the most extensively studied MSC population.MethodsMSCs were isolated and expanded from BM aspirates of hematologically healthy donors (nu2009=u200918) and from the WJ of full-term neonates (nu2009=u200918). We evaluated, in parallel experiments, the MSC immunophenotypic, survival and senescence characteristics as well as their proliferative potential and cell cycle distribution. We also assessed the expression of genes associated with the WNT- and cell cycle-signaling pathway and we performed karyotypic analysis through passages to evaluate the MSC genomic stability. The hematopoiesis-supporting capacity of MSCs from both sources was investigated by evaluating the clonogenic cells in the non-adherent fraction of MSC co-cultures with BM or umbilical cord blood-derived CD34+ cells and by measuring the hematopoietic cytokines levels in MSC culture supernatants. Finally, we evaluated the ability of MSCs to differentiate into adipocytes and osteocytes and the effect of the WNT-associated molecules WISP-1 and sFRP4 on the differentiation potential of WJ-MSCs.ResultsBoth ex vivo-expanded MSC populations showed similar morphologic, immunophenotypic, survival and senescence characteristics and acquired genomic alterations at low frequency during passages. WJ-MSCs exhibited higher proliferative potential, possibly due to upregulation of genes that stimulate cell proliferation along with downregulation of genes related to cell cycle inhibition. WJ-MSCs displayed inferior lineage priming and differentiation capacity toward osteocytes and adipocytes, compared to BM-MSCs. This finding was associated with differential expression of molecules related to WNT signaling, including WISP1 and sFRP4, the respective role of which in the differentiation potential of WJ-MSCs was specifically investigated. Interestingly, treatment of WJ-MSCs with recombinant human WISP1 or sFRP4 resulted in induction of osteogenesis and adipogenesis, respectively. WJ-MSCs exhibited inferior hematopoiesis-supporting potential probably due to reduced production of stromal cell-Derived Factor-1α, compared to BM-MSCs.ConclusionsOverall, these data are anticipated to contribute to the better characterization of WJ-MSCs and BM-MSCs for potential clinical applications.

Characteristics and predictors of outcome of spontaneous spinal epidural abscesses treated conservatively: A retrospective cohort study in a referral center

OBJECTIVEnRecent studies have shown that in carefully selected patients, conservative treatment alone can be an option in the management of spinal epidural abscess (SEA). The aim of this study was to identify prognostic factors of outcome in patients with spontaneous SEA treated conservatively.nnnPATIENTS AND METHODSnA retrospective cohort study of all patients with spontaneous SEA treated with antibiotics alone from January 2012 to December 2015 was conducted in a 1200-bed tertiary referral center. Demographic, clinical, microbiological, and radiological characteristics were analyzed. Failure of medical treatment was defined as the need for delayed surgical intervention, no neurological improvement or deterioration, death due to the infection, or relapse after hospital discharge.nnnRESULTSnWe identified 21 patients diagnosed with spontaneous SEA treated conservatively. Median age was 72 years and 10 patients were male. Eleven patients presented with radicular weakness and/or radicular sensory deficit, or incomplete cord injury. Inflammatory markers were markedly elevated in all patients. Thirteen patients were successfully treated with conservative treatment, while among 8 patients with treatment failure, 1 died due to the infection. Presence of serious neurological deficits and infection due to methicillin-resistant S. aureus (MRSA) were associated with failure of conservative treatment. Notably, neither the extension nor the location of the abscess on magnetic resonance imaging (MRI) was associated with failed medical management.nnnCONCLUSIONSnA significant proportion of patients with spontaneous SEA can respond to antibiotic treatment alone. However, in patients with infection due to MRSA or with severe neurological impairment, conservative management has an increased risk of failure.

Chitosan/gelatin scaffolds support bone regeneration

Chitosan/Gelatin (CS:Gel) scaffolds were fabricated by chemical crosslinking with glutaraldehyde or genipin by freeze drying. Both crosslinked CS:Gel scaffold types with a mass ratio of 40:60% form a gel-like structure with interconnected pores. Dynamic rheological measurements provided similar values for the storage modulus and the loss modulus of the CS:Gel scaffolds when crosslinked with the same concentration of glutaraldehyde vs. genipin. Compared to genipin, the glutaraldehyde-crosslinked scaffolds supported strong adhesion and infiltration of pre-osteoblasts within the pores as well as survival and proliferation of both MC3T3-E1 pre-osteoblastic cells after 7 days in culture, and human bone marrow mesenchymal stem cells (BM-MSCs) after 14 days in culture. The levels of collagen secreted into the extracellular matrix by the pre-osteoblasts cultured for 4 and 7 days on the CS:Gel scaffolds, significantly increased when compared to the tissue culture polystyrene (TCPS) control surface. Human BM-MSCs attached and infiltrated within the pores of the CS:Gel scaffolds allowing for a significant increase of the osteogenic gene expression of RUNX2, ALP, and OSC. Histological data following implantation of a CS:Gel scaffold into a mouse femur demonstrated that the scaffolds support the formation of extracellular matrix, while fibroblasts surrounding the porous scaffold produce collagen with minimal inflammatory reaction. These results show the potential of CS:Gel scaffolds to support new tissue formation and thus provide a promising strategy for bone tissue engineering.

Bone marrow-derived mesenchymal stem/stromal cells from patients with splenic marginal zone lymphoma are intrinsically impaired and influence the malignant B-cells

Previous studies have shown that bone marrow mesenchymal stem/stromal cells (BM-MSCs) are involved in the pathogenesis and disease progression of some B-cell lymphomas, including chronic lymphocyti...

Fibro/chondrogenic differentiation of dental stem cells into chitosan/alginate scaffolds towards temporomandibular joint disc regeneration

AbstractTissue engineering (TE) may provide effective alternative treatment for challenging temporomandibular joint (TMJ) pathologies associated with disc malpositioning or degeneration and leading to severe masticatory dysfunction. Aim of this study was to evaluate the potential of chitosan/alginate (Ch/Alg) scaffolds to promote fibro/chondrogenic differentiation of dental pulp stem cells (DPSCs) and production of fibrocartilage tissue, serving as a replacement of the natural TMJ disc. Ch/Alg scaffolds were fabricated by crosslinking with CaCl2 combined or not with glutaraldehyde, resulting in two scaffold types that were physicochemically characterized, seeded with DPSCs or human nucleus pulposus cells (hNPCs) used as control and evaluated for cell attachment, viability, and proliferation. The DPSCs/scaffold constructs were incubated for up to 8 weeks and assessed for extracellular matrix production by means of histology, immunofluorescence, and thermomechanical analysis. Both Ch/Alg scaffold types with a mass ratio of 1:1 presented a gel-like structure with interconnected pores. Scaffolds supported cell adhesion and long-term viability/proliferation of DPSCs and hNPCs. DPSCs cultured into Ch/Alg scaffolds demonstrated a significant increase of gene expression of fibrocartilaginous markers (COLI, COL X, SOX9, COM, ACAN) after up to 3 weeks in culture. Dynamic thermomechanical analysis revealed that scaffolds loaded with DPSCs significantly increased storage modulus and elastic response compared to cell-free scaffolds, obtaining values similar to those of native TMJ disc. Histological data and immunochemical staining for aggrecan after 4 to 8 weeks indicated that the scaffolds support abundant fibrocartilaginous tissue formation, thus providing a promising strategy for TMJ disc TE-based replacement.n

Surgical options for osteoporotic vertebral compression fractures complicated with spinal deformity and neurologic deficit

INTRODUCTIONnThis paper describes surgical options for Osteoporotic vertebral compression fracture (OVCF) with acute flexible or chronic rigid kyphosis, and pseudarthrosis complicated with pain and neurologic deficit.nnnMETHODSnThis study has two components. a) A prospective clinical study of surgical treatment of 31 patients (age: 69±11 years) with either acute flexible or progressive pseudarthrotic kyphosis manifested with severe pain or neurological deficit between 2010 and 2014. Eleven patients exhibited neurocompression (Frankel B, C, D). Surgery consisted in indirect reduction, kyphoplasty, and short posterior instrumentation in 28 patients and multilevel instrumentation in three. b) The second component involved a literature search of OVCF complicated with acute or painful chronic deformities and neurologic deficit, managed with open surgical approach.nnnRESULTSnIndirect reduction, kyphoplasty and short posterior stabilization can restore satisfactory anatomic alignment and neurological deficit. Multilevel instrumentation was used for rigid long kyphosis. Complications were related to a) screw pull out and junctional kyphosis (4 patients) one of the patients also developed anterior migration of cement, b) cement leakage (4 patients). L5 radiculopathy occurred in one patient. The others remained asymptomatic. The literature review concluded that corpectomy with anterior, posterior or combined instrumentations is indicated for burst fractures, or rigid kyphosis with neurocompression. Prompt decompression with anatomical alignment may restore paraplegia. Complications were germane to osteoporotic bone predisposing to hardware loosening or cut out and dislodgement of instrumentation.nnnDISCUSSIONnNeurologic deficit associated with fractures or progressive pseudarthrotic kyphosis effectively may respond to indirect postural reduction, kyphoplasty and posterior percutaneous short segment transpedicle instrumentation. For burst fractures and rigid chronic kyphosis corpectomy reconstructed with cages and anterior, or posterior or combined instrumentations can restore and maintain normal anatomy. The following guidelines for optimal surgical instrumentation have been established: To prevent screw loosening and junctional kyphosis the instrumentation should not end within the kyphotic segment. Screws for anterior instrumentation should penetrate the contralateral cortex. Multiple site of fixation or combined anterior and posterior instrumentations dissipate stresses at any one site. Augmentation of transpedicle screw fixation with cement is a sound technical principle. Cement should inserted in a doughy state with minimal pressure to prevent cement complications.