4 stem cell patents issued last week

Dear manoj kumar valluru,

Last week 4 patents of relevance to the area of stem cells were issued.

1. # 7,332,158 (Patent Spotlight), teaches how to stimulate hematopoiesis by administration of activated blood cells (T cells).

2. # 7,332,334 covers ways of increasing hematopoietic engraftment by modifying sugars on the surface of stem cells.

3. # 7,332,336 covers how to make hepatocytes from mesenchymal and embryonic stem cells.

4. # 7,332,647 how to clone fish, as well as make transgenic fish.

In The News

IL-18 in the Heart

Sunday February 17th, 2008 @ 02:36:25 EST

Indianapolis, Indiana -

It is safe to say that the actual implimentation of stem cell therapy clinically is actually more being performed for purposes of immune modulation than actually growing of new tissues. For example, mesenchymal stem cells are most advanced clinically in the USA by the company Osiris which are administering mesenchymal stem cells in Phase III trials intravenously for treatment of graft versus host disease and Crohn's, both being immunologically mediated conditions. Indeed it is known that mesenchymal stem cells can modulate inflammation through various mechanisms such as expression of HLA-G ability to induce antigen specific T cell death and stimulating the generation of suppressor T cells

Previously it has been shown that mesenchymal stem cells have activity against a variety of cardiac conditions both in animal models, as well as in various clinical trials. For example, intravenous administration of bone marrow ALLOGENEIC mesenchymal stem cells was capable of inducing an increased left ventricular ejection fraction in patients with post-infarct heart failure Of course other types of stem cells have also been demonstrated to have therapeutic activity against heart failure, such as bone marrow derived stem cells The question is, however, how do the stem cells mediate therapeutic effects?

One simple explanation is that the stem cells are becoming cardiac tissue. This has been demonstrated in certain animal models however it has also been argued that these models are artificial.

Another explanation is that the various stem cells produce growth factors, and also generate anti-inflammatory signals. But is the damaged heart actually associated with high levels of inflammatory signals? In a recent review, (Wang et al. BIOLOGY AND MECHANISMS OF ACTION OF INTERLEUKIN 18 IN THE HEART. Shock. 2007 Dec 13) the role of one particular inflammatory cytokine, interleukin-18, is described in the heart.

The authors review studies showing that:

1. IL-18 has immune modulatory effects independent of its ability to induce interferon gamma.

2. Post-infarct, IL-18 is made by a variety of cells that infiltrate as part of the inflammatory response. These including macrophages, EC, smooth muscle, neutrophils, and the cardiomyocytes.
3. Systemic rises in IL-18 are seen post infarct.

4. IL-18 induces apoptosis of various cellular components of the myocardium.

5. IL-18 is involved in myocardial hypertrophy.

6. IL-18 knockout mice do not undergo ventricular remodeling the same way that wild-types do. Specifically, the typical hypertrophic response is missing.

7. Administration of exogenous IL-18 induces hypertrophy of the ventricle.

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This Week's Patent Spotlight

Compositions and treatments for myelosuppression by ex vivo activated immune cells

Patent Number: 7,332,158

Assignee | Inventor

Failure/suppression of the hematopoietic can be a deadly consequence of over-aggressive administration of chemotherapeutics/radiotherapy. The global market for agents that stimulate hematopoiesis, particularly granulopoiesis is in the billions of dollars per year, as witnessed by the success of Amgen's Neuopgen and Neulasta products. The current patent teaches a novel, and arguably more natural way of stimulating the hematopoietic system.

Essentially the inventor covers several methods of introducing "activated" blood cells into a myelosuppressed patient in order to accelerate hematopoietic recovery. It is known that immune cells produce various cytokines involved in engraftment and stimulation of hematopoiesis. The inventor is simply thinking that synergistic efficacy may be obtained if one administers a "symphony of cytokines" as opposed to one recombinant cytokine. The patent is also interesting since administration of the activated white blood cells is not restricted to autologous blood but also to allogeneic cells.

One area of possible concern, however, is that some of the cytokines associated with activation of blood cells may actually suppress the hematopoietic system. For example, interferon gamma is known to be produced when peripheral blood mononuclear cells are activated with a calcium ionophore and a cytokine, or ligation of CD3. Interferon gamma inhibits CD34 cells and in some cases actually kills them. The same can be said for several other inflammatory cytokines, such as TNF-alpha. Perhaps the best way to improve this patent is to mix infliximab with the supernatant so as to deplete inflammatory components of the "therapeutic mix".

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