Cell transplantation therapies for spinal cord injury focusing on bone marrow mesenchymal stem cells: Advances and challenges.

Spinal cord injury (SCI) is a devastating condition with complex pathological mechanisms that lead to sensory, motor, and autonomic dysfunction below the site of injury. To date, no effective therapy is available for the treatment of SCI. Recently, bone marrow-derived mesenchymal stem cells (BMMSCs) have been considered to be the most promising source for cellular therapies following SCI. The objective of the present review is to summarize the most recent insights into the cellular and molecular mechanism using BMMSC therapy to treat SCI. In this work, we review the specific mechanism of BMMSCs in SCI repair mainly from the following aspects: Neuroprotection, axon sprouting and/or regeneration, myelin regeneration, inhibitory microenvironments, glial scar formation, immunomodulation, and angiogenesis. Additionally, we summarize the latest evidence on the application of BMMSCs in clinical trials and further discuss the challenges and future directions for stem cell therapy in SCI models.

Bone marrow mesenchymal stem cells and exercise restore motor function following spinal cord injury by activating PI3K/AKT/mTOR pathway.

Although many therapeutic interventions have shown promise in treating spinal cord injury, focusing on a single aspect of repair cannot achieve successful and functional regeneration in patients following spinal cord injury . In this study, we applied a combinatorial approach for treating spinal cord injury involving neuroprotection and rehabilitation, exploiting cell transplantation and functional sensorimotor training to promote nerve regeneration and functional recovery. Here, we used a mouse model of thoracic contusive spinal cord injury to investigate whether the combination of bone marrow mesenchymal stem cell transplantation and exercise training has a synergistic effect on functional restoration. Locomotor function was evaluated by the Basso Mouse Scale, horizontal ladder test, and footprint analysis. Magnetic resonance imaging, histological examination, transmission electron microscopy observation, immunofluorescence staining, and western blotting were performed 8 weeks after spinal cord injury to further explore the potential mechanism behind the synergistic repair effect. In vivo, the combination of bone marrow mesenchymal stem cell transplantation and exercise showed a better therapeutic effect on motor function than the single treatments. Further investigations revealed that the combination of bone marrow mesenchymal stem cell transplantation and exercise markedly reduced fibrotic scar tissue, protected neurons, and promoted axon and myelin protection. Additionally, the synergistic effects of bone marrow mesenchymal stem cell transplantation and exercise on spinal cord injury recovery occurred via the PI3K/AKT/mTOR pathway. In vitro, experimental evidence from the PC12 cell line and primary cortical neuron culture also demonstrated that blocking of the PI3K/AKT/mTOR pathway would aggravate neuronal damage. Thus, bone marrow mesenchymal stem cell transplantation combined with exercise training can effectively restore motor function after spinal cord injury by activating the PI3K/AKT/mTOR pathway.

CXCL12 and CXCR4 polymorphisms and expressions in peripheral blood from patients of hepatocellular carcinoma.

AIM: To determine if CXCL12 (rs1801157) and CXCR4 (rs2228014) polymorphisms are associated with hepatocellular carcinoma (HCC) susceptibility, and detect their expressions in peripheral blood. METHODS: 206 HCC patients, 252 chronic hepatitis B patients, 221 liver cirrhosis patients and 275 healthy volunteers were recruited. Genes CXCL12 and CXCR4 were amplified and genotyped. Their expression in peripheral blood were detected. RESULTS: CXCL12 rs1801157 and CXCR4 rs2228014 polymorphisms were associated with increased susceptibility of HCC, and genotypes GA/AA and CT/TT may be risk factors of HCC (all p < 0.05). Expressions of CXCL12 and CXCR4 in peripheral blood from HCC patients increased significantly (p < 0.05). CONCLUSION: CXCL12 and CXCR4 polymorphisms may be risk factors for HCC, and they may be potential HCC markers.

Evaluation of the single-incision Elevate system to treat pelvic organ prolapse: follow-up from 15 to 45 months.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to assess the 2-year clinical outcomes of pelvic reconstructive surgery with the single-incision Elevate system (American Medical Systems, Minnetonka, MN, USA). METHODS: This retrospective study was conducted from November 2010 to August 2013, and included 210 patients with pelvic organ prolapse stage 3 or 4 who underwent pelvic reconstructive surgery with an Elevate system and were followed for 1 to 3 years postoperatively. Assessments included pre- and postoperative Pelvic Organ Prolapse Quantification (POP-Q) stage, Urogenital Distress Inventory (UDI-6), Incontinence Impact Questionnaire (IIQ-7) and multi-channel urodynamic examinations. Anatomical success was defined as postoperative POP-Q stage 0 or I. RESULTS: The anatomical success rates were 95 % for the anterior vaginal wall, 99 % for the posterior vaginal wall and 94 % for the apical vaginal wall after a median 27 months of follow-up. POP-Q, UDI-6 and IIQ-7 scores, maximal flow rate and post-voiding residual urine all improved significantly after surgery. Complications included 1 case of internal bleeding, 4 cases of mesh exposure, 5 cases of recurrent prolapse that required salvage operations, and 3 cases of urine retention that required intermittent catheterization. There were no bladder or bowel injuries during surgery. CONCLUSIONS: Pelvic reconstructive surgery with the Elevate system yielded good anatomical outcomes and symptom improvement after 2 years of follow-up.

Medium-term comparison of uterus preservation versus hysterectomy in pelvic organ prolapse treatment with Prolift™ mesh.

INTRODUCTION AND HYPOTHESIS: We conducted a medium-term assessment of clinical outcomes and complications after surgical repair of pelvic organ prolapse (POP) using Prolift™ mesh, and sought to determine whether concomitant hysterectomy clinically influenced the outcome of pelvic reconstruction in patients without a prior history of urogenital surgery. METHODS: Patients diagnosed with POP-Q stage 3/4 uterine prolapse at a tertiary referral urogynecology unit in South Taiwan who had undergone POP repair with Prolift mesh from May 2007 to July 2010 were identified by chart review. Concomitant hysterectomy was performed in 24 patients (hysterectomy group), and uterus-sparing surgery in 78 (uterus-sparing group) Preoperative and postoperative subjective assessments of urinary and prolapse symptoms, objective POP-Q score, urodynamic examination, and postoperative adverse events were compared between the groups. RESULTS: The mean follow-up periods were 25.7 months (range 6.2 - 73.1 months) and 31.7 months (range 6.0 - 78.4 months) in the concomitant hysterectomy and uterus-sparing groups, respectively. There were no between-group differences in functional and anatomic outcomes after surgery. No statistically significant differences were found in postoperative adverse events between the groups. CONCLUSIONS: Pelvic reconstruction using Prolift with concomitant hysterectomy and uterus-sparing surgery have similar anatomic and functional results at 2.5 years. Therefore, we consider uterus-sparing surgery to be an alternative to hysterectomy in uterine prolapse repair.

[Clinical observation on the preventive effect of kangdu bufei decoction on acute severe respiratory syndrome].

OBJECTIVE: To observe the preventive protection of Kangdu Bufei Decoction (KBD) on acute severe respiratory syndrome (SARS) in medical personnel of Hong Kong at the epidemic period. METHODS: At the epidemic period of SARS in Hong Kong, there were 2,601 medical staffs administered with KBD distributed by the Center. It was confirmed that 1,063 persons had taken it for successive two weeks according to the request and returned the effective questionnaire, they were regarded as the TCM group. The control group was consisted of 15,374 subjects who didn't take Chinese herbal medicine. Contents of the questionnaire including the condition of testee in terms of quality of life (QOL), changes of influenza-like symptoms and Warm disease symptoms. Serum immunological examination had been conducted in 37 of the persons in the TCM group. RESULTS: No one in the TCM group got SARS infection while in the control group, 64 (0.4%) had got. Self-control before and after treatment examination showed that significant improvement appeared in the TCM in aspects of influenza-like and Warm disease symptoms and QOL. The results of serum immunological examination showed that after administration of KBD, the immunity of organism was improved and elevated. CONCLUSION: KBD could prevent the occurrence of SARS, it is possibly realized through improving symptoms, elevating QOL and enhancing immunity of organism.