About treating addiction with fat cells and up-regulation of CXCR4 to improve homing
I was reading the blog of Dr. Joseph Purita yesterday (January 7th 2014), who reported recently about his trip to the Swiss clinic in Moscow and the discussions he had with Russian doctors at that clinic. Highly interesting was his report that those doctors, besides treating addiction patients the traditional way, they also used fat cells for this purpose. From his blog: link here for whole article:
I was intrigued that they seemed to be having excellent success treating addiction problems by using mainly fat stem cells.Once the SVF is produced it is than treated with growth factors derived from platelet rich plasma (PRP). What happens with the PRP is that it is clotted in a test tube. Once the PRP is clotted it releases its growth factors. The growth factors are mixed with the SVF and they are given intravenously. Intravenous stem cells are used to treat a number of conditions including chronic obstructive pulmonary disease (COPD), diabetes, cardiac problems, neurological conditions and a variety of other conditions. I spoke to the Russian doctors and they feel the stem cells travel to many parts of the body including the brain. This apparently helps with the addiction problems. Their feeling is that addiction is a multi-faceted problem affecting many different portions of the body. One wrinkle that was done in Moscow was that we also used intravenous bone marrow aspirate. As I have stated many times fat tissue has more mesenchymal stem cells while bone marrow has more hematopoietic stem cells. The patient that was treated with IV SVF and bone marrow stem cells was a stroke patient. He apparently had a good result from SVF alone so it was hoped that the combination would have an even better effect.
My perspectiveFrom my perspective, this is not all that surprising, since I feel the Russian doctors could very well be correct in their assumptions, which they apparently see proven by the ensuing conditions of the patients treated. An important aspect could be (hypothesis by yours truly) that the size of the MSC progenitors derived from fat (and after becoming activated MSCs) are decisively smaller in size than cultured cells and of course also chemical small molecules. Neurological disorders have always been the graveyard for Big Pharma research, simply since the size of the molecules was substantial and those molecules could not pass the Blood Brain Barrier (BBB). Regenerative cells do have a much better chance in doing so by their sheer size and of course "being driven" by something to the site of injury, that is generally referred to as "homing". To conclude on the cell size aspect- fresh cells have a diameter of approx. 12 mu. Cultured cells almost double that- > 20 mu. On the "homing" aspect- this fact is generally recognized by scientists, but the reason why is not very clear. I just vividly remember a neat explanation by Leeza Rodriguez, based on a study with rodents where a single mouse did not respond on MSC treatment as expected and congruent to his cage companions. That is- until the fact came out that this particular mouse was dropped by a lab assistent, causing a broken (mouse) leg. The cells traveled to the broken bone and healed it very fast instead of the other inflicted injury of the study. In the blog post of Dr. Purita, a commenter note did draw my attention:
Murad wrote: Very interesting topic, this addiction treatment seems to be a result of "cxcr4 signaling" of damaged/hurted cells+tissue. With this signals SC's know where to migrate... Thanks Joe
So what is that all about?
As usual- when I do read things that catch my interest and I have never heard of or remember to have read before- I start "googling" to find answers. However I gave up after half an hour yesterday, not being able to find anything decent of an explanation. Imagine my surprise, finding a Chinese study today that specifically dealt with this subject! The study was called- Protective Effects of Mesenchymal Stem Cells with CXCR4 Up-Regulation- link here-
The aim of the study was to modulate CXCR4 expression in MSCs and to observe the effects both on secretory action and on migration and a few other things in transplanted kidneys in vivo. This interesting study concludes that amongst other things MSC therapy ameliorates the negative effects of Ischemia Reperfusion Injury (IRI) in a very strong, clinically relevant model of rat kidney transplantation at early time points. CXCR4 plays a critical role not only in the process of homing but also in the pathogenesis of acute rejection and chronic allograft nephropathy, in which both immune- and non-immune-mediated mechanisms are involved. The pretreatment to MSCs, such as using some cytokines or anoxia to up-regulate CXCR4, may facilitate the migration of infused MSCs to the site of injury and promote tissue repair.
Sounds great- again we are a little bit smarter. As a closing point- especially the pre-treatment aspect must provide industry participants in the regenerative space with a lot of frustration having to deal with current regulatory rules, which were designed in the sixties for drugs as specific small molecule compounds. Through the whole process of approval, obviously the chemical composition remains unchanged. With cell therapy a lot of tweaking is possible with the delivery method, but also with conditioning of the cells briefly before administration to a patient. I get equally frustrated when a CEO in the space tells me, he can IMPROVE dramatically on fixing the perfusion defect of an ischemia treatment and improve bloodflow with 400% by conditioning. However is stuck in developing this, since his present methods are not commercialized yet. A lot needs to be changed before cell therapy can really take off- the potential is gigantic though.