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TOPIC: Arnold Caplan Pens New Paper

Arnold Caplan Pens New Paper 22 Jul 2015 17:19 #4852

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Arnold Caplan and Robert Hariri have a new publication out in the current version of Stem Cells Translational Medicine called: "Body Management: Mesenchymal Stem Cells Control the Internal Regenerator." It is a very interesting article going over the history of research in the field and, in it, he proclaims a change in the meaning of the acronym MSC from Mesenchymal Stem Cell to Medicinal Signaling Cells. Something many here are already aware of. What I found interesting was his endorsement of the allogeniec model in this quote:

"However, from a business approach, the allogeneic repositories of companies such as Mesoblast or Athersys might provide the cell therapies of choice just in terms of the cost of goods for mass-produced therapeutic cells versus autologous cell banks. These stem cell treatments will be cost, resource, and time efficient for patients and the society as whole."

Here is a link to the paper but you need a free subscription to get the entire article.

A must read!
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Arnold Caplan Pens New Paper 23 Jul 2015 08:41 #4853

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Street would you mind just uploading article to this page. It is pdf file and is easy and will save time on the registration.
Thanks

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Arnold Caplan Pens New Paper 23 Jul 2015 08:50 #4854

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There you go


File Attachment:

File Name: 2015-Caplan-MSCcontrolIntRegulator.pdf
File Size: 976 KB
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Board moderator and Site-owner. I still regret the day I started analysing the prospects of MacroPore (now Cytori) back in 2004- a left-over from the tech-bubble at that time from the century change in my portfolio- and became addicted to Cytori´s fat cell technology. :cry:

Arnold Caplan Pens New Paper 23 Jul 2015 14:42 #4857

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Fas, an important takeaway from this article is that the medicinal characteristic of the MSC does not diminish with culturing while the regenerative capacity of an MSC does. Cytori's COGS should still be very low and the question is does it have greater a regenerative capacity than allo cells.

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Arnold Caplan Pens New Paper 27 Jul 2015 07:52 #4871

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I managed to read the article in the week-end and must say, to me, Arnold wasnt all that convincing this time.

Yes- we know the history build up from the 80ties to the present and remember the core function description of MSC mechanism of therapeutic action, which can be summarized by this image...



and which he repeats in words in the paper...

From the front of the MSCs (facing away from the damaged tissue), a curtain of molecules is secreted that stops the body’s overaggressive immune system from surveying the injured tissue behind the MSC. This is the body’s first line of defense against the establishment of a chronic autoimmune reaction. Thus, MSCs are naturally and intensely immunomodulatory; in a simplistic sense, MSCs have been called the “guardians of inflammation”].
Indeed, this curtain from human MSCs appears to function in rodent models of disease without immunosuppression of the rodent hosts. From the back of the MSCs toward the damaged tissue, a different set of bioactive molecules are secreted that function as “trophic” agents, which are grouped into 4 categories that contribute to a regenerative microenvironment. The first group consists of molecules that inhibit ischemia-stimulated apoptosis (a broken blood vessel cannot deliver oxygen to the surrounding tissue, thus stimulating ischemia-caused cell death). The second group consists of molecules that inhibit the formation of scar tissue. The third group consists of molecules, such as vascular endothelial growth factor, that bring in endothelial cells to form new blood vessels. The MSCs can then revert to their pericyte phenotype and attach to these new, fragile vessels to stabilize them. Indeed, it has been shown that MSC engraftment into injured marrow involves the MSCs taking up a perivascular location [45]. The final group includes molecules that function as mitogens for tissue-specific progenitors. In summary, we further hypothesize that these secretory or paracrine activities of MSCs will themselves change as a function of time and the local milieu.


The key statement from Caplan is really that not anything he is writing, but not saying any longer- that is the MSC is NOT responsible for (trans-) differentiation but for management according the lines described above- i.e they have a "regenerator" function, but mainly as "manager or management" i.e. still need local endogenous cells to regenerate damaged tissue according to the MSC secreted pathway.

At least thats what I read from Arnolds lines below:

The switch from the “big pharma” logic, one molecule cures all, to understanding how to manage the body’s intrinsic tissue regenerative capacity using the natural capabilities of cells such as MSCs to manage regenerative motifs will change how medicine is practiced in the future. Because MSCs play a central role in the natural repair and regeneration of almost all tissues, we strongly suggest that local MSCs help provide the microenvironment for local tissue regeneration after localized tissue injury and can be thought of as controlling the local “regenerator.”


and this one :

The therapeutic output of cell-based therapies relies both on the docking or sensing and on the cellular output in the form of secreted factors, which exert their effects in our genomically controlled endocrine or paracrine regeneration/repair capacity. By the time humans reach the age of 40–50 years, this regenerative and repair potential is greatly diminished and accounts for “late-onset” diseases or tissue dysfunction. The medical challenge is to learn how to optimize the remaining innate regenerative potential and to understand how to supplement these unique functionalities.
Such supplementation should not be viewed as the “fountain-of youth,” but rather as a means of enhancing a “good health” status while influencing human longevity, with the objective of not only living longer, but also and more importantly forestalling catastrophic health status collapse.


For the "manager" to be successful he would need his infrastructure or army of indians to do the work that the manager cannot do - to me this is were NATURAL HEALTH comes in. One needs hormones or vitaminoids to transform the building blocks of cells (protein or the hundreds of amino acids) and make the right type of cells available for the MSCs to work.

This is my study direction at present and I feel I am getting pretty close. :happy:

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Arnold Caplan Pens New Paper 27 Jul 2015 08:07 #4872

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"However, from a business approach, the allogeneic repositories of companies such as Mesoblast or Athersys might provide the cell therapies of choice just in terms of the cost of goods for mass-produced therapeutic cells versus autologous cell banks. These stem cell treatments will be cost, resource, and time efficient for patients and the society as whole."


here, I hear the entrepreneur and commercial leader Arnold Caplan speaking, since he does NOT EXPLAIN, how this should work. This allo stuff still does not make sense to me - inputting 150 Mio "managers" or 25 Mio, should not make a hell of a difference, since I believe there to be a therapeutic threshold only if the patient has the proper and sufficient receptors.

Fas, an important takeaway from this article is that the medicinal characteristic of the MSC does not diminish with culturing while the regenerative capacity of an MSC does. Cytori's COGS should still be very low and the question is does it have greater a regenerative capacity than allo cells.


Yes- "based on the management role" of MSCs, I think we are in good shape going forward- especially also when Arnold states the above like this:

Each tissue houses MSCs/pericytes that have different chemistries because of the local environments in which they are housed. The small amount of data now available suggest they all have the same sensory and response elements (immunomodulatory and trophic) even when expanded in culture under very different culture conditions. Wewere struck by this latter fact, because the differing variables, such as plating density, culture medium constituents, multiple passages, lower high oxygen, and so forth, used to culture expand MSCs from various tissues do not destroy this core capacity of immunomodulation and trophic activity, which seems to be hard-wired into these cells. In contrast, the progenitor or stem cell capacity is lost after only a few passages in culture.


Going forward, I think cell therapy is going to look a helluvalot different than it looks today, due to the chemical differences and the way Caplan teaches "mankind". I also think- regenerative medicine is going to be "all natural" and becomes a part of the practice of medicine. :grin: - except for the regulatory side in the US of course.

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Board moderator and Site-owner. I still regret the day I started analysing the prospects of MacroPore (now Cytori) back in 2004- a left-over from the tech-bubble at that time from the century change in my portfolio- and became addicted to Cytori´s fat cell technology. :cry:
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