Sunday, 21 February 2016 14:52

Half a Can of Coke

Half a can of coke of fat tissue extracted from the subcuteneous part of the belly, is the standard introduction by all presenters of Cytori managers at Investor conferences over the past eight years, when they start describing what amount of fat is needed from a patient before that fat is processed by Celution to extract a therapeutic dose of regenerative cells for a medical application.
I still do not know what size can of coke is actually referred to, but it has been stated at various occasions, that even with skinny persons it is no problem at all to harvest 250 to 300 cc of fat from the subcutaneous part of the belly. More is generally assumed to be no issue at all too.
 
In light of the recent decision by Cytori to have ATHENA II following the completion of the cardiac ischemia clinic ATHENA with a higher dose of ADRCs (most likely influenced by outside sources either FDA or potential partner) , it is certainly interesting to have a closer look at the issues surrounding the extraction of ADRCs with Celution and determine what is possible and what might provide issues. Clear is that Cytori in the past ALWAYS has preached that 20-30 Mio viable cells was most likely the optimal dose for the cardiac application, due to limited availability of endogeneous receptor cells, which are assumed to have by means of cell-to-cell interaction, its most effective therapeutic mechanism of action. 

 

To help us understand- the study by Cytori presented by Chief Scientist- John Fraser at IFATS in 2012 is most helpful and provides a solid basis for this understanding.

But first the terminology.

In the past 8 years, I have read and learned that a clinical dose of fresh cells from either bone marrow or fat were simply called nucleated cells (or mononuclear cells) and that despite the fact that some red blood cells without a nucleus were included. Since fat as a source of cells have become increasingly popular and relevant, a new designation has developed for the extracted cells- Stromal Vascular Fraction (SVF). To me totally confusing and wrong- since only a tiny portion can be called "stromal cells", but that is the way it is. So what in the past was mononuclear cells extracted from adipose tissue, is now called SVF. 

The paper from John Fraser (shortened)

Non-culture expanded adipose stromal vascular cells (SVF) are increasingly gaining acceptance as a viable cellular therapy for treatment of ischemic injury and disease. As with any new technology, numerous claims are made regarding what the therapeutic is and what it can do. Some are confirmed by rigorous validation; others are unsubstantiated, causing confusion among users. Here we report our decade of experience in determining how much SVF is actually present in human adipose, and the cellular identity of SVF cells obtained after enzymatic release from tissue 
Results:
Results: The predicted number of SVF cells obtained
per cc of fat is in the range of 3.68 Mio ± 1.55 Mio cells depending on the ratio of mature adipocytes. Enzymatic processing yielded between ~1.5 x 105 to ~10.0 x 105 SVF cells/g tissue. NucleoCounter was found to be more reproducible than live/dead cell counting. Flow data demonstrated a large variation of major cell subpopulations between individuals.
Conclusion: Characterization of SVF is Not as straight forward as some might think. Contaminating irrelevant cell populations, high interpersonal sample variability, and use of nonvalidated analysis methods contribute to the generation of misinformation about SVF that could ultimately compromise patient safety and therapy.
The last statement is clearly a hack at all the "new companies" being founded looking to jump the bandwagon of regenerative medicine based on fat cells, who claim all kinds of new ways to separate SVF from fat and yielding more and better cells in the process. Most of it is simply pure scam, all scientists of reputation confirm that the gold standard is (and most likely will stay) enzymatic digestion, which can also lead to poor results if inferior types of collagenase i.e. the enzyme which digest the tissue, is used.
So depending on the individual - 150.000 to 1.000.000 SVF cells are harvested per CC of fat. The characterization thereof can be done with SistemicQC as discussed in my previous article (Good News from Naples) and a more "practical statement" can be heard in the video from Neil Riordan, who´s talk on "fat cells" include- "from the average person we easily can take a pound of fat and extract 100 Mio SVF cells". The dose escalation as required by the FDA for the ATHENA trial to 40 Mio cells, should not provide any issue. Cosmetic surgeons often remove 4 to 6 pounds of fat from an individual.

Average composition of the harvest.

SVFThe image on the left provides an overview of the major cell populations and sub-populations extracted from fat. This type of information is rarely seen or presented by other participants in the cell therapy industry and is valuable information.  Absolute KEY to understand that:
In the case of adipose derived SVF the exact roles of all the different subpopulations when delivered in combination in vivo are still unknown.  There is evidence that macrophages and T cells in addition to the “MSC” progenitors, endothelial lineage cells and smooth muscle progenitors may all participate to some degree in improving the body’s response to acute and chronic injury.  The jury is still out as to which cell(s) is/are most important in clinical efficacy.
However in respect of individual cell types and populations a lot of research has been conducted and answers found. White blood cells or also called leukocytes, for instance appear to contain cells, the socalled Tregs, which upon activation produce armies of molecules (or cytokynes), which combat the clonal T cells, which the body produces when being attacked by its own
It is no surprise therefore that Cytori took a license for the US on the patent from Thomas Ichim- STEM CELL MEDIATED TREG ACTIVATION/EXPANSION FOR THERAPEUTIC IMMUNE MODULATION. Going forward this will be very important for applications against auto-immune disorders, which I already explained in my Hardcore article. I have had a video recording of a Neil Riordan speech on the auto immune effectiveness of fat cells now on my site for over a year. I would recommend for you to view it again- Its important- very very much so for which reason I include it in this article again.
Even more important is understanding what the 37% CD34+ and CD31- cells do (as indicated in the image above). Here we have to turn to Arnold Caplan, but doing so merits another detailed explanation in a separate blog article, which will follow soon. In the mean time - you can watch the new "Video of the year"- featuring Caplan on this site at the left hand side column of most pages - just click and it enlarges.
 
Last modified on Monday, 22 February 2016 05:02

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