TOPIC: Injected PLGA microspheres with autologous fibroblasts

Hi!

I have been reading this forum for a while and I wanted to share an idea that I had. I\'m not sure this is the right sub-forum to put this topic, but since the stem-cell database should probably be restricted to sharing links that didn\'t seem like a good fit either. Anyway, feel free to move it. =)

After looking into autologous fibroblasts (this technique has been shown to be viable for penile girth enhancement in several studies, both on humans www.ncbi.nlm.nih.gov/pubmed/21164145 , www.ncbi.nlm.nih.gov/pubmed/16310926 , www.ncbi.nlm.nih.gov/pubmed/20796201 and on animals www.term.or.kr/journal/view.php?number=236 ) I got to some thinking. For those of you who haven\'t explored this as obsessively as I have, fibroblasts are the cells which synthesize connective tissue (part of which is collagen) in the body and autologous means that the cells are from the patient who will receive them which removes the problem of rejection and inflammatory reactions. The basis of this method is that after taking a small biopsy of scrotal skin and culturing fibroblasts on a tube-shaped scaffold made of PLGA, a biodegradable material, the PLGA scaffold is surgically implanted and the fibroblasts will then start generating new tissue. The disadvantages are the invasive surgical techniques required for implanting the tube-shaped PLGA scaffold and possibly the difficulty in predicting gains of the procedure. Cost could be imagined to be a prohibitive factor, but in fact there is a patented and FDA approved autologous biofiller called Laviv that calls for twice the amount of fibroblasts as used in the studies (~20 million) and which carries a total treatment price of about $3-4000 (and that is to the plastic surgeon).

My idea, admittedly not a huge leap, was to replace the PLGA scaffold tube with PLGA microspheres that are mixed with cultured autologous fibroblasts. One study in rabbits has shown that injected PLGA microspheres mixed with chondrocytes (cartilage producing cells, which are about the same size as fibroblasts) produced healthy cartilage after implantation: \"Four and 9 weeks after implantation, chondrocytes implanted with PLGA microspheres formed solid, white cartilaginous tissues, whereas no gross evidence of cartilage tissue formation was noted in the control groups. Histological analysis of the implants by hematoxylin and eosin staining showed mature and well-formed cartilage.\" This appears to suggest that the structure provided by grouped microspheres as opposed to a cohesive tube can also support the growth of viable tissue. www.ncbi.nlm.nih.gov/pubmed/15869422

Another study has shown that PLGA microspheres when injected into mice were not associated with migration and remained at their site of injection: \"After injection of PLGA microspheres into the subcutaneous dorsum of mice, inflammation, new tissue volume change, and microsphere migration were examined. Host cells from the surrounding tissues migrated to the implanted microspheres and formed new hybrid tissue structures. The volume of the newly generated tissues was maintained approximately constant for 7 weeks. Histological analyses showed no evidence of migration of the implanted microspheres to the distant organs. In summary, PLGA microspheres were injectable and able to induce a new hybrid tissue formation without initial volume decrease or particle migration.\" www.ncbi.nlm.nih.gov/pubmed/15449255

The significance of this could be that instead of surgically implanting a PLGA scaffold tube, microspheres mixed with fibroblasts could be injected (presumably even with a microcanula) in the same way as PMMA. In addition to being a much less invasive procedure this could perhaps allow for greater control of the amount of girth gained by varying the amount or concentration of the microspheres and/or fibroblasts and for a more gradual process by repeated injections as opposed to a single major surgical procedure.

I can\'t really be the judge of whether this is a good idea but it might be something worth exploring. What\'s your take on this?

hoddle10 wrote: By the way, you could email Miro Djordvevic and ask him what he thinks about using injectable PLGA instead. I\'m sure he\'d reply.

I will do that. I am also interested in what Cassavantes would think about this (if he even has the time to reply, lol), even though it is somewhat far from what he practices. He is a Dermatologist though and probably has some knowledge or experience of Laviv, as well as something to say about PLGA microspheres in general.

But if we don\'t want to believe Perovic, then we have to keep in mind that research teams in China, at least two of which affiliated with the university hospital in Beijing, have reached the exact same results with fibroblast or ADSC treatment in both humans and animals in several studies. I also have a hard time to believe that his studies, which were published in international journals, were simply falsified, and I think it\'s much more likely that procedures which individual patients later received did not live up to the standard in the studies.

And even if we bring patient bias into the issue (which goes against the reports that penile Girth was measured, not just subjectively assessed), that of course has absolutely no relevance for the animal studies.

By the way, you could email Miro Djordvevic and ask him what he thinks about using injectable PLGA instead. I\'m sure he\'d reply.

This guy had the scaffold in Thailand and I\'m pretty sure they use the scrotal method there as well. I\'ve sent him a PM to check, but he doesn\'t log on very often, so don\'t know if we\'ll get a reply. But his result was just a 1cm gain, which was in line with the other results and less than half what was claimed in the Perovic study.

phalloboards.websitetoolbox.com/post/Ive...2?highlight=thailand

It could well be down to poor technique, but I certainly don\'t believe the Perovic study has any value. If you\'d met the Perovic team you\'d probably think the same. They are liars plain and simple. If the claims they make about the results with the blood serum are as far fetched as they seem, then why should we believe the results from their initial studies? Also before I had the procedure, another member, \"mikehok\" emailed one of the Korean dr\'s involved in the original studies and he claimed that most patients couldn\'t see any gains. He put this down to penis dysmorphia, but with hindsight that seems ridiculous and not in line with the thinking we see from our members here, many of which clearly have mental issues regarding their penis size. We\'ve had guys unhappy with procedures for all sorts of reasons, but I don\'t think I\'ve ever come across a trend of guys not being able to see gains, even though they are there. Most measure obsessively.

That would seem to contradict the latest animal study (where PLGA and PLGA + stem cell implantations were directly compared and only the latter worked), and also the fact that the general principle of tissue engineering through cell injection with a PLGA scaffold is sound and works for at least cartilage and bone whereas the implantation of PLGA alone thus far hasn\'t been shown to give anything whether anecdotally or in studies. I am no one to speak against Dr. Atala but I am curious to what he really has to back up his statement with (there seems to absolutely nothing and on the other hand a fair amount of evidence for the complete opposite). As for individual treatments that haven\'t worked, I would attribute that to incomplete (or simply skipped, in one way or the other) cell cultures rather than a fundamental flaw in the technique.

When it comes to the Perovic biospy and whether it can be trusted or not I will try to look in the other studies (if I find the full articles) if biopsies were performed there also.

target8x6 wrote: But why would the implantation of PLGA alone result in any new tissue except for what is generated through inflammatory response, which may or may not be permanent? The biopsies by Serovic in his second study using scrotal skin-derived fibroblasts showed new tissue \"closely resembling\" that of the dartos fascia, and this is actually consistent with other studies where the injection of chondrocytes seeded on PLGA forms cartilage, osteoblasts create bone etc.. I haven\'t found any comparative studies where only PLGA was injected and the resulting tissue was biopsied and its volume followed over time, but I will continue to look as that could give us a lot of clues. However I\'m fairly confident that the PLGA-only approach might work to create some new tissue, but that there is no reason that the inclusion of viable fibroblasts wouldn\'t result in greater gains.

I\'m just still not convinced that at least four different studies are wrong or falsified based on anecdotal evidence where patients may not even have had the full procedure. In fact I found another animal study which arrives at the same results, but using adipose-derived stem cells instead of fibroblasts: www.amepc.org/tau/article/view/433/484

Edit: On second thought and after looking more closely there was actually a very interesting finding reported in the study I just brought up: There was a group which received a non-stem cell cultured Maxpol (PLGA) scaffold that saw no statistically relevant change in penile girth compared to the control group, whereas in the group that received stem cells it was \"augmented significantly\".

I don\'t know, but Dr Atala has done more tissue engineering with PLGA than anyone else and he told Dr Reed that he didn\'t think the scaffolds even need to be treated.

I\'d be skeptical of anything said in the Perovic study. Aside from Bonehead, there was a member of the old Yahoo group who also had the scrotal tissue method and he didn\'t gain anything either. The Perovic team still offer the scrotal method if people want it, but swear it makes no difference.

But why would the implantation of PLGA alone result in any new tissue except for what is generated through inflammatory response, which may or may not be permanent? The biopsies by Perovic in his second study using scrotal skin-derived fibroblasts \"closely resembled\" (though I am not completely sure that it was new tissue that was biopsied) normal tissue of the dartos fascia, and this is actually consistent with other studies where the injection of chondrocytes seeded on PLGA forms cartilage, osteoblasts create bone etc.. I haven\'t found any comparative studies where only PLGA was injected and the resulting tissue was biopsied and its volume followed over time, but I will continue to look as that could give us a lot of clues. However I\'m fairly confident that the PLGA-only approach might work to create some new tissue, but that there is no reason that the inclusion of viable fibroblasts wouldn\'t result in greater gains.

I\'m just still not convinced that at least four different studies are wrong or falsified based on anecdotal evidence where patients may not even have had the full procedure. In fact I found another animal study which arrives at the same results, but using adipose-derived stem cells instead of fibroblasts: www.amepc.org/tau/article/view/433/484

Edit: On second thought and after looking more closely there was actually a very interesting finding reported in the study I just brought up: There was a group which received a non-stem cell cultured Maxpol (PLGA) scaffold that saw no statistically relevant change in penile girth compared to the control group, whereas in the group that received stem cells it was \"augmented significantly\".

Dr Atala doesn\'t even think the scaffolds need to be treated at all, so I doubt the fact the scrotal cell technique wasn\'t used made any difference. Also we have a member called \"Bonehead\" and he had the scrotal technique and it made no difference at all.

I had the Perovic procedure in Serbia. It was performed by Miro Djordevic.

Here is a link to the thread where this was discussed a few weeks ago.

phalloboards.websitetoolbox.com/post/Gro...-5606061?trail=30#19

I\'d be tempted to inject a small amount myself if I could get hold of it.

That\'s also something that could work, though as you say there have been many disappointing reports about the use of PLGA scaffolds for penile Girth enhancement. However at the very least the injection of microspheres would be a less invasive procedure and easier to repeat than the implantation of new tube scaffolds.

I\'m a bit confused however by some of the reports I read at the old forum as they don\'t seem to mention a scrotal skin biopsy followed by a cell culture which must have taken several weeks, if not months. That has made me wonder if some of these procedures have not been fibroblast implantations at all but rather some sort of compromise. That might explain the differences in results and is in my opinion much more likely than falsified data in the studies. What kind of procedure was it that you had and where was it (if I may ask)?

I had the same thought and read the same studies. My thinking was slightly different though, as I\'ve had PLGA scaffolds and gained nothing. I know others that have had similarly disappointing results, so I\'m not convinced of it\'s tissue engineering capability in this application. My thinking was that perhaps the microspheres would behave in a similar way to PMMA or Radiesse. I mentioned a couple of weeks ago that idea of finding an injectable that would dissolve and leave a permanent scar capsule and that is when the idea of injectable PLGA cam to mind. I also thought it could be useful when fixing things such as adhesions.

target8x6 wrote: But if we don\'t want to believe Perovic, then we have to keep in mind that research teams in China, at least two of which affiliated with the university hospital in Beijing, have reached the exact same results with fibroblast or ADSC treatment in both humans and animals in several studies. I also have a hard time to believe that his studies, which were published in international journals, were simply falsified, and I think it\'s much more likely that procedures which individual patients later received did not live up to the standard in the studies.

And even if we bring patient bias into the issue (which goes against the reports that penile Girth was measured, not just subjectively assessed), that of course has absolutely no relevance for the animal studies.

I definitely don\'t. Look at the studies published for things such as fat transfer. They get published in international journals and the results seem in complete contrast to what we see in the real world. I think another Serbian Dr (Panolev I believe), reported in the European Journal of Urology, that his Girth enhancement procedure with fat transfer had a satisfaction rate at over 90%! It\'s just pure bullshit.

I\'m not saying that PLGA tissue engineering doesn\'t work. Dr Atala\'s results suggest otherwise. But I am saying the Perovic study is close to worthless. Quite a few people have had surgery with the Perovic team and you\'ll struggle to find anyone who has had surgery with them, that has anything good to say about them. In the hands of someone like Dr Atala, we might well see very different results, to what we\'ve seen with Perovic and Djordevic and thus is could very well be down to flawed technique, but I seriously doubt that Perovic and his team ever produced anything like the results they claimed in their studies. It just seems much more plausible that a bunch of known liars, simply lied about their results, than actually had good results and then changed their technique for the worse.