Zeinab M. El Maadawi

Autologous Bone Marrow-Derived Cell Therapy Combined With Physical Therapy Induces Functional Improvement in Chronic Spinal Cord Injury Patients

Spinal cord injuries (SCI) cause sensory loss and motor paralysis. They are normally treated with physical therapy, but most patients fail to recover due to limited neural regeneration. Here we describe a strategy in which treatment with autologous adherent bone marrow cells is combined with physical therapy to improve motor and sensory functions in early stage chronic SCI patients. In a phase I/II controlled single-blind clinical trial (clinicaltrials.gov identifier: NCT00816803), 70 chronic cervical and thoracic SCI patients with injury durations of at least 12 months were treated with either intrathecal injection(s) of autologous adherent bone marrow cells combined with physical therapy or with physical therapy alone. Patients were evaluated with clinical and neurological examinations using the American Spinal Injury Association (ASIA) Impairment Scale (AIS), electrophysiological somatosensory-evoked potential, magnetic resonance imaging (MRI), and functional independence measurements. Chronic cervical and thoracic SCI patients (15 AIS A and 35 AIS B) treated with autologous adherent bone marrow cells combined with physical therapy showed functional improvements over patients in the control group (10 AIS A and 10 AIS B) treated with physical therapy alone, and there were no long-term cell therapy-related side effects. At 18 months posttreatment, 23 of the 50 cell therapy-treated cases (46%) showed sustained functional improvement. Compared to those patients with cervical injuries, a higher rate of functional improvement was achieved in thoracic SCI patients with shorter durations of injury and smaller cord lesions. Therefore, when combined with physical therapy, autologous adherent bone marrow cell therapy appears to be a safe and promising therapy for patients with chronic SCI of traumatic origin. Randomized controlled multicenter trials are warranted.

Treatment of dystrophic epidermolysis bullosa with bone marrow non‐hematopoeitic stem cells: a randomized controlled trial

Patients with dystrophic epidermolysis bullosa (DEB) have mutations in type VII collagen gene. Type VII collagen is synthesized by keratinocytes and fibroblasts. Based on the ability of bone marrow non‐hematopoeitic stem cells (NHBMSC) to develop into fibroblasts, we decided to investigate the use of NHBMSC in the treatment of recessive DEB (RDEB). This study included fourteen patients with RDEB; the first seven of them were given cyclosporine after the infusion of NHBMSC. As cyclosporine has been used for the treatment of RDEB we decided not to use cyclosporine for the second group of seven patients. Skin biopsies from the lesions were studied by electron microscopy before and after treatment. The number of new blisters decreased significantly after treatment in both groups (p = 0.003 and 0.004 respectively) and the rate of healing of new blisters became significantly faster after treatment in both groups (p < 0.001) with no significant difference between the two groups. Electron microscopic examination revealed increased number of anchoring fibrils after treatment in both groups. No major side effects were reported during the 1‐year follow‐up period. Our findings highlight the efficacy as well as the safety of NHBMSC in the treatment of RDEB.

Increased tissue leptin hormone level and mast cell count in skin tags: a possible role of adipoimmune in the growth of benign skin growths.

BACKGROUND Skin tags (ST) are common tumors. They mainly consist of loose fibrous tissue and occur on the neck and major flexures as small, soft, pedunculated protrusions. Decrease in endocrine, hormone level and other factors are thought to play a role in the evolution of ST. Leptin is an adipocyte-derived hormone that acts as a major regulatory hormone for food intake and energy homeostasis. Leptin deficiency or resistance can result in profound obesity and diabetes in humans. A role of mast cell in the pathogenesis of ST is well recognized. AIMS To investigate the role of leptin in the pathogenesis of ST and to clarify whether there is a correlation between mast cell count and leptin level in ST. METHODS Forty-five skin biopsies were taken from 15 patients with ST. From each patient, a biopsy of a large ST (length >4 mm), a small ST (length <2 mm) and a normal skin biopsy (as a control) were taken. The samples were processed for leptin level. Skin biopsies were stained with hematoxylin and eosin and toluidine blue-uranyl nitrate metachromatic method for mast cell count was used. RESULTS There was a significant increased level of leptin in the ST compared to the normal skin. It was highly significant in small ST than in big ST (P = 0.0001) and it was highly significant in small and big ST compared to controls, P = 0.0001 and P = 0.001, respectively. There was a significant increase in mast cell count in the ST, which did not correlate with the increased levels of leptin. CONCLUSION This is the first report to demonstrate that tissue leptin may play a role in the pathogenesis of ST. The significant increase in the levels of leptin and mast cell count in ST may indicate a possible role of adipoimmune in the benign skin growths.

Intrathecal Transplantation of Autologous Adherent Bone Marrow Cells Induces Functional Neurological Recovery in a Canine Model of Spinal Cord Injury.

Spinal cord injury (SCI) results in demyelination of surviving axons, loss of oligodendrocytes, and impairment of motor and sensory functions. We have developed a clinical strategy of cell therapy for SCI through the use of autologous bone marrow cells for transplantation to augment remyelination and enhance neurological repair. In a preclinical large mammalian model of SCI, experimental dogs were subjected to a clipping contusion of the spinal cord. Two weeks after the injury, GFP-labeled autologous minimally manipulated adherent bone marrow cells (ABMCs) were transplanted intrathecally to investigate the safety and efficacy of autologous ABMC therapy. The effects of ABMC transplantation in dogs with SCI were determined using functional neurological scoring, and the integration of ABMCs into the injured cords was determined using histopathological and immunohistochemical investigations and electron microscopic analyses of sections from control and transplanted spinal cords. Our data demonstrate the presence of GFP-labeled cells in the injured spinal cord for up to 16 weeks after transplantation in the subacute SCI stage. GFP-labeled cells homed to the site of injury and were detected around white matter tracts and surviving axons. ABMC therapy in the canine SCI model enhanced remyelination and augmented neural regeneration, resulting in improved neurological functions. Therefore, autologous ABMC therapy appears to be a safe and promising therapy for spinal cord injuries.

The possible role of trauma in skin tags through the release of mast cell mediators

Background: Skin tags (ST) are common benign tumors of the skin but their etiopathogenesis is not well understood. STs arise in sites subjected to trauma. It was proved that mast cells are recruited to sites of skin trauma and increase their tumor necrosis factor-α (TNF-α) content. Aim: STs are linked to obesity and frictional sites, but this has not been studied at the molecular level. We hypothesized that mast cells, TNF-α and its family member, TNF-related apoptosis-inducing ligand (TRAIL) might play a role in the pathogenesis of STs as a response to trauma. Materials and Methods: A study was done on 15 patients with STs. Two STs and a snip of normal skin were obtained in each subject. We counted the mast cells after Toluidine blue staining. Enzyme-linked immunosorbant assay was used to measure TNF-α level while reverse transcriptase polymerase chain reaction was used to evaluate the level of TRAIL mRNA expression. Results: Mast cell count in all STs was significantly higher than that in control (P=0.0355). There was a highly significant increase in the level of TNF-α in all STs as compared to its level in controls (P<0.0001). Expression of TRAIL mRNA was significantly higher in STs as compared to its expression in controls (P<0.0001). Conclusion: Our study suggests that mast cells, TNF-α and TRAIL may play a role in the pathogenesis of STs.

A Tale of Two Cells: Telocyte and Stem Cell Unique Relationship

Telocytes have been identified as a distinctive type of interstitial cells and have been recognized in most tissues and organs. Telocytes are characterized by having extraordinary long cytoplasmic processes, telopodes, that extend to form three-dimensional networks and commonly constitute specialized forms of cell-to-cell junctions with other neighboring cells. Telocytes have been localized in the stem cell niche of different organs such as the heart, lung, skeletal muscle, and skin. Electron microscopy and electron tomography revealed a specialized link between telocytes and stem cells that postulates a potential role for telocytes during tissue regeneration and repair. In this review, the distribution of telocytes in different stem cell niches will be explored, highlighting the intimate relationship between the two types of cells and their possible functional relationship.

Effect of human cord blood-derived stem cells on induced diabetic retinopathy in adult albino rat: histological and immunohistochemical study

Background Diabetic retinopathy is a leading cause of blindness in adults. Recent developments in stem cell field have widened the prospects of applying cell-based therapies to regenerate ocular tissues. Aim of the study This study was done to explore the potential effect of human cord blood-derived stem cells on induced diabetic retinopathy in adult albino rats. Methods This study was performed on 26 adult male albino rats. Animals were randomly divided into four groups. Group I (control group): five control animals each received single intraperitoneal injection of citrate buffer. Group II: seven animals in whom diabetes was induced by single intraperitoneal injection of streptozotocin and animals were killed 4 weeks later. Group III: seven animals in whom diabetes was induced the same way as in group II and animals were killed 8 weeks later. Group IV: seven animals with diabetes were injected with ferrous oxide-labeled cord blood-derived stem cells 4 weeks after induction of diabetes and were killed 4 weeks after stem cell injection. All sections from retina of all groups were subjected to Haematoxylin and eosin, Prussian blue staining and CD34 immunohistochemistry. Statistical analysis was done to measure the mean number of ganglion cell nuclei and the wide clear areas around them. Results Groups II and III showed progressive histological changes of diabetic retinopathy. Group IV exhibited a significant increase in the number of ganglion cells with less clear areas compared with group III. Moreover, cells positive for Prussian blue and CD34 were detected in different retinal layers of group IV. Conclusion Human cord blood-derived stem cells injected into rats with diabetic retinopathy contributed to restoration of ganglion cell layer and vascular repair, which may postulate a potential therapeutic intervention for diabetic retinopathy.

CXCL-10 and Interleukin-6 are Reliable Serum Markers for Vitiligo Activity: A Multicenter Cross-Sectional Study.

This cross‐sectional multicenter study aimed to evaluate serum CXCL‐10, as an activity marker for vitiligo, and compare it with other putative serum and tissue markers. Serum CXCL‐10 was compared to interferon gamma (IFN‐γ), interleukin 6 (IL‐6), and IL‐17 using ELISA in 55 non‐segmental vitiligo patients (30 active and 25 stable) and 30 healthy controls. Marginal skin biopsy was taken for immunohistochemical evaluation of CD8+T cells and CXCL‐10+ve cells. Serum levels of CXCL‐10, IL‐17, and IL‐6 were elevated in all vitiligo patients compared to controls (p < .05). All investigated serum markers were higher in active versus stable vitiligo. Tissue expression of CXCL‐10+ve cells and CD8+ve T cells was stronger in vitiligo patients compared to controls, and tissue CXCL‐10+ve cell expression was stronger in active versus stable cases. Positive correlations were noted between the different serum and tissue markers. CXCL‐10 was the most specific, whereas IL‐6 was the most sensitive serum marker to distinguish active from stable disease.

Effect of Procedural-Related Variables on Melanocyte-Keratinocyte Suspension Transplantation in Nonsegmental Stable Vitiligo: A Clinical and Immunocytochemical Study.

BACKGROUND Melanocyte–keratinocyte suspension (M–K susp) is gaining popularity for vitiligo treatment. Few studies have addressed procedure-related variables. OBJECTIVE To assess the effect of different M–K susp procedure-related variables on the clinical outcome in stable vitiligo. METHODS This prospective multicenter comparative study included 40 cases with nonsegmental stable vitiligo. Donor site was either a skin graft in noncultured epidermal cell suspension (NCECS) or hair follicle units in outer root sheath hair follicle suspension (ORSHFS). Recipient site was prepared by either cryoblebbing or CO2 laser resurfacing. Cell counts and viability were recorded in the cell suspensions. Tissue melanocytes and keratinocytes were examined by melan-A and cytokeratin, respectively. Assessment of repigmentation was performed 18 months after the procedure. RESULTS Thirty-seven subjects completed the study. Cell count was significantly lower in the ORSHFS compared with NCECS with no significant difference in the repigmentation outcome. On comparing techniques of recipient site preparation, homogenicity was better in the CO2 group. Elbows and knees responded better to CO2 resurfacing, whereas distal fingers responded better to combination of cryoblebbing with NCECS. CONCLUSION Using different techniques in M–K susp produces comparable results. However, the distal fingers showed better results using combination of donor NCECS and recipient cryoblebs.

Histological and quantitative morphometric evaluation of striae distensae treated by long-pulsed 1064-nm Nd: YAG laser

BackgroundStriae distensae are frequent undesirable skin lesions that result in considerable esthetic concern. Treatment has always been challenging. Several modalities are available; however, none of them is consistently effective. Laser has become a popular therapeutic alternative. ObjectiveThe aim of this study was to evaluate the possible therapeutic effect of a long-pulsed 1064 nm Nd:YAG laser in striae distensae using histological and quantitative morphometric studies. Patients and methodsForty female patients with striae (group I: striae rubra and group II: striae alba) were included. All patients received four laser sessions at 4-week intervals. Three skin biopsies were obtained from every patient: one from normal control skin, the second from the selected striae before treatment, and the third from the same striae 1 month after treatment. Paraffin-embedded skin sections were subjected to histological and quantitative morphometric studies for assessment of collagen and elastic fibers. ResultsIn both groups, some clinical improvement was achieved, which was statistically nonsignificant. However, histological examination showed increased collagen and decreased elastic fibers with reorganization after treatment. The image analyzer showed a significant quantitative increase in the mean area percent of collagen fibers and decrease in the mean area percent of elastic fibers. Side effects were nonsignificant, mostly pain during the session and pigmentary alterations. ConclusionAlthough the clinical improvement in the treated striae was nonsignificant, the histological improvement was significant, with few side effects. The use of different laser parameters with a long follow-up period may improve the clinical response.