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  • ISSN: 2379-0490
    Volume 3, Issue 1
    Review Article
    Kurata Hayato1,2, Tamai Rie1,2, Katsuda Takeshi1, Ishikawa Shumpei3, Ishii Tsuyoshi2 and Ochiya Takahiro1*
    Stem cell therapy, including mesenchymal stem cell (MSC) therapy, is a promising therapeutic option for treating several diseases. Adipose tissue-derived mesenchymal stem cells (AT-MSCs) have been identified as a candidate for stem cell therapy. Sources of MSCs include bone marrow, umbilical cord, amniotic fluid, and adipose tissue. Adipose tissue can be easily harvested using procedures that are minimally invasive compared with those used to obtain the other sources, and it is suitable for regenerative medicine treatments.
    End-stage cirrhosis and chronic liver failure are life-threatening liver diseases. Liver transplantation is an effective therapy for end-stage liver disease, but most patients are unable to undergo liver transplantation because of the limited supply of donors, the complex surgical procedure, rejection, pre-existing disease recurrence, and high costs.
    AT-MSCs are a promising candidate for regenerative medicine to treat liver cirrhosis. Over the past decade, the literature on non-clinical studies and clinical trials for liver diseases has been accumulating, and we can speculate on the efficacy and safety of MSC therapy. The mechanisms of the curative effects of AT-MSCs have been clarified insufficiently. However, a large number of reports indicate that the hepato-protective effect of AT-MSCs is related to a paracrine effect of soluble mediators rather than the differentiation potency of the cells. In this review, we summarize the efficacy and safety of AT-MSC use and the current preclinical studies and clinical trials of AT-MSCs.
    Research Article
    Itzhak Binderman1,2*, Dar Weiss2, Rona Katzengold2, Joseph Choukroun4, Nasir Gadban1 and Avinoam Yaffe3
    Abstract: Local treatment with extracorporeal shock waves (ESW) evokes an acute trigger of inflammation, promoting generation of bone in non-union bone fractures. Our aim was to find a correlation between the amount of applied ESW pulses and their effect on tissue engineering of bone. We applied different number of pulses of electrohydraulic shock wave device at 0.1mJ/mm2 flux energy to activate bone marrow cells grafted with TCP/HA (ReproBone) scaffold, to generate bone in an ectopic subcutaneous site of DA rats. In sham control, bone is generated ectopically within 3 weeks after grafting. Application of 300 pulses of ESW at time of grafting surgery reduced by 20-30% the amount of bone, while application of 500 or 1000 pulses totally inhibited osteogenesis. When 300 pulses were applied 4 days after grafting, bone generated more efficiently than in sham controls. Also, effects on viability and metabolism of human vascular endothelial cells (HUVEC) were measured in response to ESW pulses. Direct application of 0,100, 300 pulses of ESW on HUVEC cells in culture showed 3 hours later an increased metabolic activity, between 77±3% to 82±3.5%. Application of 600 and 1200 pulses inhibited metabolic activity and reduced significantly cell viability. It seems that a threshold exists where more than 300 pulses have a detrimental effect on cell viability. In conclusion, our findings indicate that ESW is effective tool in activating bone generation when applied at the site of bone grafting 4-6 days after surgery, by 300 or less pulses.
    Andrei Kochegarov*, Ashley Moses-Arms, Michael C. Hanna and Larry F. Lemanski
    Abstract: The Mexican axolotl, Ambystoma mexicanum, is a unique vertebrate species which has amazing powers of limb regeneration. In the present study we have used a Subtractive Amplification approach to identify genes which are activated and overexpressed during the limb regeneration process. In our initial studies, we have found that levels of expression of 11 genes are increased during the limb regeneration process. This group includes Cellular retinoic acid-binding proteins (CRABP1 and CRABP2), Retinal dehydrogenase 2 isoform 4, Homeobox protein MSX-2, Bone morphogenetic protein, BMP2, Homeobox protein MEOX-2, LIM homeobox transcription factor 1-alpha, LMX1A, Fibroblast growth factors (FGFR4 and FGFR8) and some others. Thus, our data support the hypothesis that retinoic acid and Epidermal Growth Factors may be a morphogens that plays an important role in proximodistal limb patterning.
    Yuemin Tian, Jerry Wright, Liudmila Cebotaru, Hua Wang and William B. Guggino*
    Abstract: Anoctamin 5 (Ano5), which belongs to anoctamin gene family, was recently identified as calcium activated chloride channel (Ca CC). Mutations in theAno5 gene cause limb-girdle muscular dystrophy (LGMD) 2L, which is associated with defective sarcolemma membrane repair.Ano5 is localized mostly in intracellular vesicles and also on plasma membrane (PM), but the underlying mechanism of how Ano5 interacts with PM repair remains undefined. From our study, exposure of CFBE and HEK293 cells to 0.01% saponin solution for one minute triggered Ano5 protein accumulation at the PM. This observation indicated that Ano5 inclusive vesicles may transfer to the surface of the cell during PM disruption, and participate in forming the patch to seal and repair the PM. Calcium influx during PM disruption may trigger vesicle localized Ano5 activation, and Cl- transportation may be the signal that leads these vesicles to travel to the damaged PM. In summary, we demonstrated that Ano5, which functions as a Ca CC, is recruited to the PM during the wound healing, and this observation can explain the defective sarcolemma membrane repair in patients with mutations in Ano5.
    Amir Oron1 and Uri Oron2*
    Abstract: Regenerative capacity following injury or an ischemic event is confined to non mammalian vertebrates. Mammals have a limited capacity to restore organs following injury to organs like the liver and skeletal muscles but practically no ability to regenerate organs like the heart or brain following an ischemic event or injury. We tried a new approach in cell based therapy to improve regeneration in various organs following ischemic injury. Low-level laser therapy (LLLT) which has photobiostimulating effects on cells was delivered to autologous bone marrow (BM) that is enriched with stem cells and various progenitor cells, in order to induce the cells in the BM for the benefit of the injured /ischemic organs. In a model of induced myocardial infarction (MI) in rats laser application to the BM caused a marked and significant decrease (79%) in infarct size (scarring) 3 weeks post-MI. It was also found that a significantly higher density of c-kit positive cells (a marker of mesenchymal stem cells) in the myocardium of laser-treated rats relative to non-treated rat's post-MI. The novel approach presented in this study, of the use of stem cells for cell therapy to the infracted heart, avoids the need to isolate millions of stem cells, to grow them in vitro and to inject them back into the patient. In the same line of rationale we tried to find whether LLLT to the BM could be beneficial also to kidney impairment after ischemic reperfusion injury (IRI) to the rat kidney. C-kit positive cell density in kidneys post-IRI and laser-treatment was significantly (p=0.05) 2.4-fold higher compared to the non laser treated group. Creatinine, blood urea nitrogen, and cystatin-C levels were significantly lower in the laser-treated rats as compared to non-treated ones. The effect of LLLT delivery to BM was also tested on Alzheimer's disease (AD) mice in their late stage of the disease. Mice were given multiple (every 10 days) LLLT to BM from age 4 to 6 months. It was found that in the treated AD-mice neurological tests (Fear and Cognitive tests) revealed a significantly (p<0.05) better neurological performance and cognitive capacity compared to the non-treated AD mice. Furthermore, concomitantly with the improved neurological performance, ß-amyloid density in the hippocampal region of the brains was revealed to be significantly less in the laser-treated mice as compared to control. In conclusion, a novel approach, of applying LLLT to autologeous BM in order to induce stem cells that are consequently recruited to the injured/ischemic organ leading to a marked beneficial effect post-ischemic event or degenerative process is presented. This approach is novel in the respect that it is stimulating the patient's own abilities to initiate a regenerative response in an organ by the utilization of light. The possibility that this approach can also be applied to other ischemic/injured organs or organs undergoing degenerative processes (i.e. neurodegenerative diseases), with consequent beneficial effects, cannot be ruled out
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