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scistats 6301 posts  |  Last Activity: Jul 17, 2014 3:01 PM Member since: Apr 5, 2009
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  • scistats scistats Jul 17, 2014 3:01 PM Flag

    Biotechs are volatile and self correcting. A bad trial result, and we all know the consequences. What Yellen has done is strategically break the legs of the sector in a planned, strategic, targeted hit. And she can hit again. If this is coordinated, we can get hit in other ways. The money is on the move, the biotech lamb has been slaughtered.

    Sentiment: Strong Buy

  • She certainly did a good job of poisoning America's innovative drug pipeline. People's heads are now on the chopping block and clinical trials will be shuttered in some cases. She did long-term strategic damage with a goal of moving money from one place to another. She has done long term damage to biotechs in the US. This is a historic set back.

    Sentiment: Strong Buy

  • Reply to

    Dark humor to liven the mood.

    by scistats Oct 22, 2013 8:32 PM
    scistats scistats Jul 9, 2014 3:11 AM Flag

    Cool!

    Sentiment: Strong Buy

  • Transplanted cells afford benefit via a systemic rather than localized effect.
    -Journal of Neuroinflammation 2012, 9:228

    Evidence to the central role of the spleen (and lung) in MAPC-mediated neuroprotection.
    Cannot deliver IA because of risk of blocking vessels.

    IV infusion is what we are doing and then MAPC-mediate neuroprotection is directed from the lung and spleen.

    Sentiment: Strong Buy

  • scistats scistats May 17, 2014 2:19 PM Flag

    The FDA and lawyers no longer have absolute control.
    This is the first crack in bureaucratic grid lock and frivolous lawsuits.

    Sentiment: Strong Buy

  • New law.
    Access to Imetelstat.
    Perfect timing.
    Can't wait till the lawyers suing Geron find out!

    Sentiment: Strong Buy

  • scistats scistats May 17, 2014 1:58 PM Flag

    Right to try.

    Sentiment: Strong Buy

  • Will this include MultiStem for stroke in the near future?

    Sentiment: Strong Buy

  • MultiStem Cells Versus MSC
    Mesenchymal stromal cells (MSC) may use similar immunosuppression mechanisms (Gebler et al., 2012) and although MAPC and MSC exert comparable activity in an in vitro T-cell suppression assay (Jacobs et al., 2012), it is evident that they are distinct cell types. Both cells are adherent bone marrow-derived stem cells, but due to different culture conditions they adopt different phenotypes (Roobrouck et al., 2011b). The cells express distinct cytokine profiles which may explain the observations that MAPC can induce tube formation by HUVEC cells in in vitro assays while MSC lack this pro-angiogenic effect (Lehman et al., 2012). Moreover, MAPC are able to induce functional blood vessels in vivo when the cells are implanted in a Matrigel plug with VEGF and bFGF under the skin of nude mice, where vessels induced by MSC appeared leaky (Roobrouck et al., 2011a). This latter study showed by means of transcriptome analysis that MAPC and MSC are clearly distinguishable cells types. In a recent study, intracranial injection of human MAPC and human MSC 2 days after induction of stroke revealed that MAPC had a stronger effect on the attenuation of the inflammatory response and had more potency to promote endogenous tissue regeneration than MSC (Mora-Lee et al., 2012).

    Sentiment: Strong Buy

  • Conclusions
    In summary, we demonstrate that transplantation of hMSCs and hMAPCs mediate neuroprotection during the acute phase of ischemic stroke and prevents delayed brain injury through several therapeutic effects, such as angiogenesis, diminished inflammation and scarring, as well as, increased SVZ cell proliferation and neuroblast survival close to the ischemic area. Therapeutic effects mediated by cell transplantation do not require long-term cell engraftment and are likely related to the secretion of growth factors and cytokines.

    Sentiment: Strong Buy

  • Our data show that the intravenous injection of bone marrow-derived MAPC increases the percentage of T regulatory cells within the spleen. The observed increased in T regulatory cells could potentially modulate the systemic inflammatory response leading to preferential differentiation of microglial/macrophage cells into the neuroprotective M2 phenotype. The in vitro data support the concept that soluble factors influenced by MAPC:splenocyte interactions affect microglia/macrophages by decreasing overall proliferation and apoptosis, by specifically increasing apoptosis of proinflammatory microglia and converting microglia/macrophages towards an anti-inflammatory phenotype.

    Overall, we believe that our data again confirm the central role of splenocytes in the observed neuroprotection seen with progenitor cell therapy, thereby providing further evidence that the transplanted cells afford benefit via a systemic rather than localized effect.

    Sentiment: Strong Buy

  • In conclusion, IA delivery of stem cells offers the advantage of directly targeting the damaged tissue, and circumvents the problem of cell trapping in filtering organs such as the lung, liver, or spleen. However, it needs to be emphasized that the IA delivery represents a paradox, as the goal is to achieve a high cellular engraftment without inducing microvascular occlusions and compromising cerebral blood flow. In this article we have demonstrated that despite the benefits of intraarterial delivery of stem cells to the ischemic brain, there is a clear risk of vascular occlusion. Thus, noninvasive monitoring methods as described in this study are mandatory for possible clinical translation of IA stem cell delivery in stroke patients.

    Sentiment: Strong Buy

  • Still other factors, such as injection site, timing and cell number administered, may also affect the engraftment and therapeutic effects of MSCs that are depending on the specific disease status. The various routes of injection that have been tried, including intravenous, intraperitoneal, intra-arterial and in situ, each affects the efficiency of MSC homing or localization to target organs.98 Among them, intravenous delivery is convenient and successful in treating certain type of diseases, but better engraftment efficiency can sometimes be obtained by intra-arterial and in situ injections, such as myocardial infarction, kidney transplantation and brain injury.104, 105, 106, 107 Administration of MSCs in situ, although highly sometimes effective in both engraftment and therapy, is less clinically applicable as it is so invasive and introduces cells in a microenvironment that could be unsuitable for survival.108 In another study, in spinocerebellar ataxia, intravenous transplantation was more effective in promoting the survival of cerebellar Purkinje cells and MSC engraftment than that of intracranial injection.109 The intraperitoneal injection route has been rarely used, but some recent studies used it to treat muscular dystrophy and IBD in the mouse model, resulting in effective engraftment and therapeutic effects.110, 111, 112 Therefore, when MSCs are used to treat distinct diseases, their administration routes should be well-selected. Another influence on MSC effectiveness is the stage of disease: delivery of MSCs at an early stage following an event causing ischemia or EAE has shown enhanced engraftment rates or therapeutic effects, whereas administrated at the relapse stage of EAE, their beneficial effects are reduced.64, 93, 113 Finally, the dose of MSC administration should also be considered, because more MSC administration does not show a better therapeutic effect in the brain injury animal model.55

    Sentiment: Strong Buy

  • scistats scistats May 16, 2014 12:48 AM Flag

    Hi Centurycom,

    Roger that.

    We just have to hope that macrophages with immunoregulatory function (following phagocytosis of dead MultiStem in the lung) go to the site of the stroke and modulate inflammation.

    Macrophages can go anywhere, but because the patient's immune system is very critical here, the health of the immune system is a major factor.

    This brings us to the exclusion criteria: ClinicalTrials.gov has an abbreviated list, but in fact the exclusion criteria is much more lengthy. Google the YouTube statment: "Stem Cell Therapy in Acute Ischemic Stroke" and we see the guys in Houston present the actual unabridged exclusion criteria.

    This list requires otherwise healthy individuals, so I think we are safe to assume that those enrolled can indeed mount an army of these macrophages to quell the stroke damage...despite the MultiStem not making it beyond the lung and only debris of these cells making it to the liver.

    I think we have a shot here. What do you think?

    Sentiment: Strong Buy

  • Yes they can, but the question remains: Is one dose of MultiStem sufficient to get enough of these anti-inflammatory M2 phenotype macrophages on target to resolve damage?

    ...I surely hope so. IA delivery would be more effective, but it is possible IV may work.

    Sentiment: Strong Buy

  • scistats scistats May 15, 2014 6:48 PM Flag

    Now for the mechanism:
    We have shown that pMSCs can transition macrophages from an inflammatory M1 into an anti-inflammatory M2 phenotype. Our findings suggest a new immunosuppressive property of pMSCs that may be employed in the resolution of inflammation associated with inflammatory diseases and in tissue repair.

    Sentiment: Strong Buy

  • The old dogma that administered MSC engraft and differentiate in specialized cell types has been abandoned, whereas the proposition that the effects of MSC are mediated via the secretion of trophic and immunoregulatory factors has gained in popularity.

    Our data clearly demonstrate the short-term survival of infused MSC and a lack of distribution of viable MSC beyond the lungs. Nevertheless, several studies have demonstrated beneficial effects of MSC in a variety of disease models (Gonzalez et al., 2009; Semedo et al., 2009; Kanazawa et al., 2011) even when MSC were no longer around (Yang et al., 2012). The question now arises how these effects are mediated. It seems clear that delivery of MSC to a site of injury is not required for a therapeutic effect. It has been hypothesized that apoptosis of infused cells can trigger an immunomodulatory response (Thum et al., 2005) and recently it was demonstrated that macrophages adapt an immunoregulatory function after phagocytosis of dead (MSC) (Lu et al., 2012). Our results suggest this process may happen in the lungs and from there develop into a response that eventually targets the immune response at sites of inflammation and injury.

    Sentiment: Strong Buy

  • scistats scistats May 14, 2014 11:45 PM Flag

    We have shown that pMSCs can transition macrophages from an inflammatory M1 into an anti-inflammatory M2 phenotype. Our findings suggest a new immunosuppressive property of pMSCs that may be employed in the resolution of inflammation associated with inflammatory diseases and in tissue repair.

    Sentiment: Strong Buy

  • The old dogma that administered MSC engraft and differentiate in specialized cell types has been abandoned, whereas the proposition that the effects of MSC are mediated via the secretion of trophic and immunoregulatory factors has gained in popularity.

    Our data clearly demonstrate the short-term survival of infused MSC and a lack of distribution of viable MSC beyond the lungs. Nevertheless, several studies have demonstrated beneficial effects of MSC in a variety of disease models (Gonzalez et al., 2009; Semedo et al., 2009; Kanazawa et al., 2011) even when MSC were no longer around (Yang et al., 2012). The question now arises how these effects are mediated. It seems clear that delivery of MSC to a site of injury is not required for a therapeutic effect. It has been hypothesized that apoptosis of infused cells can trigger an immunomodulatory response (Thum et al., 2005) and recently it was demonstrated that macrophages adapt an immunoregulatory function after phagocytosis of dead (MSC) (Lu et al., 2012). Our results suggest this process may happen in the lungs and from there develop into a response that eventually targets the immune response at sites of inflammation and injury.

    Sentiment: Strong Buy

  • Reply to

    I Can Not Believe

    by biotechfan73 May 12, 2014 11:38 PM
    scistats scistats May 13, 2014 1:40 AM Flag

    Intravenous delivery results in first pass trapping of stem cells in the lungs and liver.

    Period.

    Osiris has over 20 years of experience with MSC's, and their technology pioneered by Dr. Arnold Caplan of Case Western Reserve University focuses on supernatant approaches. If you are going to go IV, you better be enriching (juicing), otherwise you will never achieve full efficacy.

    This Osiris patent states:
    "A method of reducing an immune response to a transplant in a recipient by treating said recipient with an amount of mesenchymal stem cells effective to reduce or inhibit host rejection of the transplant. The mesenchymal stem cells can be administered before, at the same time as, or after the transplant. Also disclosed is a method of inducing a reduced immune response against a host by foreign tissue, i.e., graft versus host disease, by treatment with mesenchymal stem cells."

    NOW, what may surprise you is that the title of this patent is:
    "Supernatant from mesenchymal stem cells for prevention and treatment of immune responses in transplantation"

    YES IT IS THE CONCENTRATED SUPERNATANT THAT IS WORKING. Subtle trade secrets of enriching the juice that MSC are floating around in upon delivery. The cells help a little, the concentrated juice from the cell helps a lot.

    You state that, "I personally think that when the data is fully analyzed that the UC trial protocol will be adapted, re-tested and prove significance benefits against the disease..."

    REALLY??? We just need another Phase 2?
    Now who is going to fund this trial, and what would you change in the protocol to ensure that it actually works, because remember Osiris saw results in their bowel trial.

    MultiStem MAY provide SOME benefit to stroke victims if administered by IV, but we can increase the odds of success dramatically by administering IA and by enriching (juicing) with supernatant.

    Now, do you want to succeed here or do you just want to keep beeautching about the Jr. Scientist?

    Sentiment: Strong Buy

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