1 stem cell patent issued last week

Dear manoj kumar valluru,

Last week 1 patent of relevance to the area of stem cells were issued.

1. # 7,319,035 (Patent Spotlight), covers novel scaffolds for implantation of stem cells.

In The News

Importance of the Injury Signal

Wednesday January 16th, 2008 @ 18:02:21 EST

Warsaw, Poland -

The immune system is activated in response to Danger signals, which evoke various innate molecular pathways that culminate with inflammatory cytokine production and eventual activation of the adaptive immune system. Stem cells circulating in lymphatics have been implicated in recognizing classical danger signals such as toll like receptor agonists which induce their differentiation into dendritic cells. It would make sense that other danger signals exist in the body that induce homing of stem cells to injured areas and in some cases stimulate their differentiation into tissues that are needed.

One example of a signal generated by injured tissue is VEGF which is generated after myocardial infarctions and clinically is associated with mobilization of bone marrow derived stem cells. Another signal is stromal derived factor (SDF-1), which is generated by hypoxic or injured tissue. Normally SDF-1 is produced at a constitutive rate by bone marrow stromal cells. This is why it is possible to inject intravenously hematopoietic stem cells into recipients of bone marrow transplants and the stem cells still home to the bone. In fact, abrogating the CXCR4-SDF-1 interaction by small molecule inhibitors leads to mobilization of stem cells, as was patented by Anormed in patent 7,169,750 Interestingly if one co-cultures stem cells with SDF-1 before administration, the stem cells have a higher potency for cardiac repair

A very important point in regards to generation of stem cell chemoattractants by damaged tissue is to figure out kinetics and biological relevance. A recent paper (Czarnowska et al. Expression of SDF-1-CXCR4 axis and an anti-remodelling effectiveness of foetal-liver stem cell transplantation in the infarcted rat heart. J Physiol Pharmacol. 2007 Dec;58:729-44) tackled this question.

Researchers induced infarcts by cutting off coronary circulation and assessed the infaract area at several timepoints. In some of the rats the investigators implanted fetal liver stem cells at various times post infarct.

Expression of SDF-1 in the peri-infarct zone peaked at day 2 after infarct and returned to normal levels at day 21 as assessed by immunohistochemistry. Cells expressing the SDF-1 receptor CXCR-4 and CD133 (resembling endogenous stem cells) also peaked at day 2. Interestingly if rats were pretreated with the Anormed compound (AMD1300) which abrogates CXCR-4 binding to SDF-1, the number of CXCR-4 positive, CD133 positive cells in the myocardium was decreased. This suggests that SDF-1 being generated by the injured tissue was actually increasing mobilization and homing of stem cells to the injured area.

Administration of the fetal liver stem cells in rats that did not recieve an infarct caused eventual loss and undetectability after 21 days. In contrast, which the stem cells were injected in rats that recieved an infarct, especially when they were injected on day 2 post infarct, the cells survived, caused a further increase in SDF-1 expression and resulted in an improved cardiac profile. Specifically, only the day 2-post infarcted injected cells were capable of inhibiting ventricular wall dilation and also stimulated angiogenesis in the infarct area.

These data suggest the importance of the tissue injury signal in homing of stem cells naturally, but also in determining optimum times for administration of stem cells. The investigation of novel danger signals involved in stem cell activity, such as the TNF alpha family member TWEAK as well as investigating ways of increasing stem cell chemoattractive ability is bound to provide new research directions and means of increasing efficacy of stem cell therapy.

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This Week's Patent Spotlight

Biological scaffolding material

Patent Number: 7,319,035

Assignee | Inventor

There are numerous patents issued on generation of scaffolds for the implantation of cells into a host in need of therapy. For example, Ethicon's patent 7,091,191 teaches the generation of hydrophobic polymers of hyaluronic acid that are superior to previous hyaluronic acid compositions since the the hydrophobicity extends the half-life of the polymer. Patent 6,995,013 belonging to BioMed Solutions teaches generation of scaffolds with 5 layers that are resemble more physiological scaffolds. As a matter of fact there are at least 79 US patents issued that teach the generation of various three dimensional matrices and scaffolds

The current patent, teaches a novel method of generating such scaffolds. Specifically the patent calls for a 4 step process. The first step involves obtaining cells (not just stem cells), the second teaches to dissociate the cells so that one has a composition of cells and debris from the cells, the thirds step states that one should place the mixture of cells and cell debris under conditions that allow for the cells to remain viable so that a “living biological matrix" is formed, the forth step states to reove the culture media that the "living biological matrix” was maintained in.

This sounds like a very broad claim that could cover many approaches to the development of matrices. If one looks at the examples, one sees that indeed the applications of this technology are numerous.

Example 1 teaches the use of the approach for cartilage repair.

Example 2 teaches spinal cord repair

Example 3 teaches making of islets

Example 4 shows the islets made in example 3 work in vivo

Example 5 teaches the generation of biological matrices made from blood

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