NuVasive to carry Osteocel

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The question that everyone should be asking themselves is not how many stem cells are present at the time of manufacture, but how many stem cells are present at the time of implantation.
 






Anonymous said:
On a slightly modified, but somewhat related topic... I hear that hospitals are struggling with the price increase Medtronic pushed through for InFuse earlier this year. As a result, Osteocel has been getting more looks and ganing market share. Can anyone verify? Comments please!
Click to expand...

i work as a neuro C.S.T.
i do see one product slowly edging the other one out.
i see and use both. (and others)
 












Concerned Scientist said:
Osteocel Plus Package Insert
Description
"Osteocel Plus (Cellular Bone Matrix) HCT/P is a formulation of cryopreserved cancellous chips, viable cancellous matrix and ground bone matrix. The native cell population retained as a result of the proprietary process has the potential to differentiate inot tissues of mesenchymal origin, including bone. Note: though well charcterized in the scientific literature, preservation of these cells in the product may not be indicative of clinical outcome."

OK. Let's break this down a bit (unfortunately you cannot post the package insert as an attachement but if someone has a link that would be excellent).

Where does it say cortical bone? How about demineralization? NO WHERE.

Where are growth factors for bone stored - cortical bone. How are they exposed? Demineralization. Is demineralized tissue considered minimally manipulated? NO. Oh, that is a problem.

"Native Cell population," huh? I thought it was up to 250,000 MSCs/cc. Instead, a much more scant reference to random native cells with the "potential" to change into (differentiate may be too big a word for some) tissues of mesenchymal origin. Wait does that mean that they could turn into cartilage and adipose (fat) tissue as well? How many MSCs are native again? About 500-1500/cc depending on donor.


Check out the new article out of JBJS 91:1073-1083. 2009. "Mesenchymal Stem Cell Concentration and Bone Repair: Potential Pitfalls from Bench to Bediside"
It is enlightening. It leaves some room for wishful thinking and objectively outlines the results of the study. But at these levels of stem cells (up to 20,000/cc) in a rat model at that, there is a long road to climb. Perhaps, this is why Osteocel does not have any of its own product published in respected journals. You might just get a glimpse of the wizard behind the curtain.
Click to expand...

Concerned Scientist,

I believe your thought process is partially correct! The difference between Osteocel and Osteocel plus is the validation! However, is th evalidation even relavant! Through the process of Selective Immunodepletion the "other cells" RBC, White Cells, etc.. are removed! This in theory leaves the STEm Cells! From different sources I have spoken with the cell count after the process is far greater than 250,000 MSC! Probbaly closer to 700,00 depending upon many factors..age, health, lifesyle, etc.. The question is how pure are these cells! MCS's can be further subdivided in 4 catergories as you noted! Bone, Tissue, Cartilage, Adipose tissue, and in addition Cardiac tissue!

The transitory process of growing bone goes thru the cartilage linage phase! In otherwords to grow bone you must go thru the tissue-cartilage-bone phase! The signal of the bon ein the body being the highest! Therefore it is easy to make MSC flip to a progenitor cell when put around a host (bone) with a high signal! What causes th eprogenitor cell to decide to be on or the other is the amount of surrounding Growth factors present to get it to make it's decision. Bone having the highest signal! The real science is figuring out how to further immunodeplete The MSC into bone, CArtilage, Adipose cells! Truly then can you claim pure cell viablity!

All of the products use cancellous bone as a host or carrier for the MSC's to bind! The signal of the product is minimal due to the fact that the MSC can turn directly into a Progenitor cell and then into transitory osteoblast usin gthe bodies own signalling of growth factors to come in via platlets and lay down growth factors!!!

Basically, all of these products are th esame with a great "new" marketing spin put on Osteocel PLUS!

To the previous poster in reference to MTF vs Osiris! That is not the issue! Allosource is a far superior tissue bank to MTF and this can be found in the simple fact that they have a validated process to Sterilize tissue and they only get donors from 5 OPO's. Plus they process in class 5 clean rooms!

Also, i'm curious how MTF will spin their Cryopreserven, Unpurged, Cancellous as a Stem Cell product that doesn't have Allogenic response!! Good luck with that one!!
 






It is nice to hear from someone with a little more knowledge than spitting insults.

You say thought that the difference between Osteocel and Osteocel Plus is the validation. So are you suggesting that Osteocel wasn't validated? I don't think so, but anyway I get the whole immunodepletion deal and partly buy that. However, your numbers on the stem cell count is far from accurate - and thus Nuvasive's/Osiris' presentation of those numbers are far from accurate as well.
I don't have to speak to anyone but instead look at the basic anatomy of the human body and what we know from research.
First, refer to this link
http://www.engin.umich.edu/class/bme456/bonestructure/bonestructure.htm
Go down to the volume of bone in the human body. The reference goes back to chapter of a book by Jee et al from 1983 on Histology. The cancellous bone is 350,000 mm^3 (350 cm^3 or 350cc). The average porosity of cancellous bone is 80% (95% to 40%). SO you have a total yield of 280cc of bone marrow aspirate in the human donor cadaver.
Another reference by a Radiological Society suggested 540cc of total cancellous bone in the body (436cc marrow). Let's stick with 280cc for now.
Second, refer to one of the leaders in aspiration research with Muschler et al.
One of his key papers is online for free at
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1424877
They gathered a natural level of 365 to 500 osteoprogenitors per cc of aspirate (the higher levels found in the deep part of the pedicles rather than the iliac crest). This is the average of 186 samples.
So taking 500 stem cells/cc with 280cc of possible aspirate and you get a total of 140,000 stem cells in the cadaver.
If you take really high levels of cancellous bone aspirate (500cc) with really high stem cell levels (1500/cc), you still only get 750,000 stem cells - barely enough for 3cc of Osteocel product if you concentrated it all down. And since Osteocel does not combine lots and does not culture the stem cells, how can you ever have a 5cc product let alone a 1cc offering at the 140,000 more realistic level.
If you can explain this argument away, then I am willing to listen. I need more real evidence than "from different sources I have spoken with."

And yes endochondral bone formation is the most common especially when micromotion is in effect. But under rigid circumstances, some osteoinductive agents (and yes it is BMP-2, the most widely studied product out there for bone grafting regardless) have been shown to actually grow intramembrous bone formation by directly translating mesenchymal cells into osteoblasts. Although, BMP-2 does most of its process through endochondral because of the micromotion that exists in the cage, or when a nail is used, or in the posterolateral space, etc. The animal models back it up.

And a yes a signal is needed. The amount of turnover of mesenchymal cells because of their environment is small. Not to mention that one of the biggest factors of BMP-2 is that it encourages replication of stem cells, Cheng et al - he studied all 14 BMPs at that time and compared them. So more and more cells are made not just however many you can claim may or may not be there.

But I digress so I get back to the main point, if you can explain away the apparent lack of enough stem cells in the human cancellous bone on average, then please do so. I am all ears. Thanks for honest dialogue.
 






Concerned Scientist

Your not by Chance in Anchorage, Ak??? If you are hello Doc!!!!!!!!!!!!!!!




Concerned Scientist said:
It is nice to hear from someone with a little more knowledge than spitting insults.

You say thought that the difference between Osteocel and Osteocel Plus is the validation. So are you suggesting that Osteocel wasn't validated? I don't think so, but anyway I get the whole immunodepletion deal and partly buy that. However, your numbers on the stem cell count is far from accurate - and thus Nuvasive's/Osiris' presentation of those numbers are far from accurate as well.
I don't have to speak to anyone but instead look at the basic anatomy of the human body and what we know from research.
First, refer to this link
http://www.engin.umich.edu/class/bme456/bonestructure/bonestructure.htm
Go down to the volume of bone in the human body. The reference goes back to chapter of a book by Jee et al from 1983 on Histology. The cancellous bone is 350,000 mm^3 (350 cm^3 or 350cc). The average porosity of cancellous bone is 80% (95% to 40%). SO you have a total yield of 280cc of bone marrow aspirate in the human donor cadaver.
Another reference by a Radiological Society suggested 540cc of total cancellous bone in the body (436cc marrow). Let's stick with 280cc for now.
Second, refer to one of the leaders in aspiration research with Muschler et al.
One of his key papers is online for free at
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1424877
They gathered a natural level of 365 to 500 osteoprogenitors per cc of aspirate (the higher levels found in the deep part of the pedicles rather than the iliac crest). This is the average of 186 samples.
So taking 500 stem cells/cc with 280cc of possible aspirate and you get a total of 140,000 stem cells in the cadaver.
If you take really high levels of cancellous bone aspirate (500cc) with really high stem cell levels (1500/cc), you still only get 750,000 stem cells - barely enough for 3cc of Osteocel product if you concentrated it all down. And since Osteocel does not combine lots and does not culture the stem cells, how can you ever have a 5cc product let alone a 1cc offering at the 140,000 more realistic level.
If you can explain this argument away, then I am willing to listen. I need more real evidence than "from different sources I have spoken with."

And yes endochondral bone formation is the most common especially when micromotion is in effect. But under rigid circumstances, some osteoinductive agents (and yes it is BMP-2, the most widely studied product out there for bone grafting regardless) have been shown to actually grow intramembrous bone formation by directly translating mesenchymal cells into osteoblasts. Although, BMP-2 does most of its process through endochondral because of the micromotion that exists in the cage, or when a nail is used, or in the posterolateral space, etc. The animal models back it up.

And a yes a signal is needed. The amount of turnover of mesenchymal cells because of their environment is small. Not to mention that one of the biggest factors of BMP-2 is that it encourages replication of stem cells, Cheng et al - he studied all 14 BMPs at that time and compared them. So more and more cells are made not just however many you can claim may or may not be there.

But I digress so I get back to the main point, if you can explain away the apparent lack of enough stem cells in the human cancellous bone on average, then please do so. I am all ears. Thanks for honest dialogue.
Click to expand...
 












I have sold Infuse, Osteocel, putty, aspirate and TCP. After all of this I can honestly say I have no idea what to recommend to a doctor for cervical or lumbar lateral fusions. If the number of cells in bone is insufficient, why is ICBG still the most effective and safe?
 






not so concerned scientist said:
Concerned Scientist,

I believe your thought process is partially correct! The difference between Osteocel and Osteocel plus is the validation! However, is th evalidation even relavant! Through the process of Selective Immunodepletion the "other cells" RBC, White Cells, etc.. are removed! This in theory leaves the STEm Cells! From different sources I have spoken with the cell count after the process is far greater than 250,000 MSC! Probbaly closer to 700,00 depending upon many factors..age, health, lifesyle, etc.. The question is how pure are these cells! MCS's can be further subdivided in 4 catergories as you noted! Bone, Tissue, Cartilage, Adipose tissue, and in addition Cardiac tissue!

The transitory process of growing bone goes thru the cartilage linage phase! In otherwords to grow bone you must go thru the tissue-cartilage-bone phase! The signal of the bon ein the body being the highest! Therefore it is easy to make MSC flip to a progenitor cell when put around a host (bone) with a high signal! What causes th eprogenitor cell to decide to be on or the other is the amount of surrounding Growth factors present to get it to make it's decision. Bone having the highest signal! The real science is figuring out how to further immunodeplete The MSC into bone, CArtilage, Adipose cells! Truly then can you claim pure cell viablity!

All of the products use cancellous bone as a host or carrier for the MSC's to bind! The signal of the product is minimal due to the fact that the MSC can turn directly into a Progenitor cell and then into transitory osteoblast usin gthe bodies own signalling of growth factors to come in via platlets and lay down growth factors!!!

Basically, all of these products are th esame with a great "new" marketing spin put on Osteocel PLUS!

To the previous poster in reference to MTF vs Osiris! That is not the issue! Allosource is a far superior tissue bank to MTF and this can be found in the simple fact that they have a validated process to Sterilize tissue and they only get donors from 5 OPO's. Plus they process in class 5 clean rooms!

Also, i'm curious how MTF will spin their Cryopreserven, Unpurged, Cancellous as a Stem Cell product that doesn't have Allogenic response!! Good luck with that one!!
Click to expand...


I hate to burst your bubble, but MTF processes in a class 10 clean room. And has first refusal rights for tissue at over 60 major donor sites across the united states. Additionally, MTF does not terminally sterilize tissue due to the potential for osteoinductivity to be compromised in this process. No, it hasn't been proven, but nobody has done a study on it and I think we all know the true answer here.... Aseptic processing is fine if your donor quality is good, test the tissue for bacteria and disease, and then process it.. in a natural allograft form.

How many recalls has MTF had on their tissue? Thanks
 






Does this debate really matter? Data for Biomimetic's Augment (recombinant human Platelet-Derived Growth Factor, or rhPDGF-BB) has been phenomenal with quick, excellent bone formation in radial and foot/ankle fractures. Eventually, the company plans to move into other indications, including spine. Why doesn't Augment become the new standard once it reaches the market place? Is there any dirt on this product?
 






Let's see... Proactively sterilize the allograft tissue to device level standards or maintain aseptic processing and hope for the best.

One example...
Check out the Progenix DBM product. They do e-beam sterilization with the final DBM product. They then take that final product (every lot) and put it in a live athymic rat model and let it be for 28 days. Only if actual bone grows (osteoinductive) do they release the lots - no petri dish reaction here. So any concerns that sterilization makes it no longer osteoinductive are mute. I think that I would take proactive sterilization rather than take my chances with aseptic only.

Also...
You are right, there are not that many recalls associated with tissue harvesting aseptically. But 1 is enough in my book if it relates to the safety of the tissue. MTF had one posted 12/16/1998. They released 45 tissues that were recalled because the donor tested reactive for HIV. Another recall on 10/7/2004 for tissue testing positive for salmonella arizonii. Another recall reported 4/16/2008 had tissues testing positive for Clostridium Perfringens. Do a search for FDA recalls on www.fda.gov.
 






Anonymous said:
Does this debate really matter? Data for Biomimetic's Augment (recombinant human Platelet-Derived Growth Factor, or rhPDGF-BB) has been phenomenal with quick, excellent bone formation in radial and foot/ankle fractures. Eventually, the company plans to move into other indications, including spine. Why doesn't Augment become the new standard once it reaches the market place? Is there any dirt on this product?
Click to expand...

still time will tell on this product. FDA is just now reviewing 2 parts of their PMA, but the clinical results won't be submitted until late 2009. If you know any early results of the larger study, then please share. What was the protocol for the study? What types of specific fractures were investigated?
 






Anonymous said:
I hate to burst your bubble, but MTF processes in a class 10 clean room. And has first refusal rights for tissue at over 60 major donor sites across the united states. Additionally, MTF does not terminally sterilize tissue due to the potential for osteoinductivity to be compromised in this process. No, it hasn't been proven, but nobody has done a study on it and I think we all know the true answer here.... Aseptic processing is fine if your donor quality is good, test the tissue for bacteria and disease, and then process it.. in a natural allograft form.

How many recalls has MTF had on their tissue? Thanks
Click to expand...

you really don't know what the hell your talking about obviously! How about MTF voluntary recall 2 years ago of 2800 grafts Jackass!!!!!!!! By the way class 10 clean rooms are not even the standard anymore! Class 5 is the standard and there are over 20 papers on the effects of collagen on Terminal sterilization!Only radiation over 1.8mrads damages tissue! Osteoinduction and Tissue???? WHAT??? Tissue is just a scaffold!!!!! MTF doesn't terminally sterilize because they don't have the technology!! They also pre dose process most grafts by the way as well smart guy!! Oh yeah and they do it at 2.5 mrads which has been shown to damage collagen!!
 






Wow, interesting discussion, but some assumptions were made when you did your number of stem cells calculation. Your numbers were correct vis a vis bone "aspirate" but that is not where the MSC's are coming from in the Trinity Evolution (or the Osteocel) the majority are attached to the cancelous bone itself which is processed whole not aspirated. It's no science secret how to identify a stem cell, or how to check if it's alive. So what we have here is about 250,000 cells/cc of which 50,000 or so are MSC's. There are plenty of other cells that can be present, like osteocytes etc.
 






Anonymous said:
Does this debate really matter? Data for Biomimetic's Augment (recombinant human Platelet-Derived Growth Factor, or rhPDGF-BB) has been phenomenal with quick, excellent bone formation in radial and foot/ankle fractures. Eventually, the company plans to move into other indications, including spine. Why doesn't Augment become the new standard once it reaches the market place? Is there any dirt on this product?
Click to expand...

I work for synthes and two of my foot/ankle accounts have moved over from Trinity/Infuse/etc. to doing Biomet's stem cell kit. (Sorry, don't know the name of it, it changed from Marrowstim to something else recently) They launched a technique for calcaneal aspiration and are distributing a ton of literature showing that the 3 bone healing/growing requirements are met with BMA and DBM. I'm not sure what their DBM is like, I know that Biomet and Biomet Trauma both have a DBM, I think that they're two different ones. Not sure, don't get the "two Biomets" thing. Anyway, now pods can pull their own stem cells vs. having md's do it for them. I asked him how many product managers he had to bring out to his meeting with the purchasing person to get his BMA in and he said that all he had to do was tell them that basically every single allograft/stem cell product states on their inserts that autologous grafting products are the gold standard HOWEVER, if one is not possible, the rest are better than nothing. I just stick to trying to keep their plates/screws biz.
 












Anonymous said:
I am scheduled to have Osteocel Plus and can not find a site for any possible side effects. Can some one please offer a site URL for me?
Thanks
Click to expand...

Your main possible "Side Effect" is disease transmission. With a product like this, you need to weigh the pro's and con's in with it.
Do you have any present health issues that might warrant the need to expose yourself to something like this?

Are you a diabetic?
Is this a revision surgery?
Are you a smoker?
Are you older?
How many levels of surgery are you having done?

There are many reasons to justify use, as well as many reasons to not use products like these?

What kind of surgery are you having done?

Also, do a google search for "osteocel bone graft contraindications." You'll find info, but think of it all as information for you to digest and decide on your own. Just because you'll download and read published articles... It doesn't mean the article isn't biased. Usually a company(manufacturer, or competitor) paid to have the research done, so make sure you make up your own mind.
 






Hey everyone who's still following this thing.
I used to work on Trinity Evolution and though I've left my former employer for greener pastures I can respond to several questions posed.

1. The original Trinity (or whatever you'd like to call it) didn't have ANY viable MSC (mesenchymal stem cells) in it's final product. The count that they used to mention (50,000) was the amount that they would register prior to the processing. Now, I know that's disappointing to hear but what was worse is that whomever brokered the deal for manufacturing Trinity Evolution decided to state the minimum # or MSCs in the final product (instead of just saying that it would be at least equivalent to the original Trinity). So you may probably be able to imagine the chagrin of the R&D folks who had to have the 50,000 MSC in the final product which is now known as Trinity Evolution. We struggled and ran many, many studies trying to figure out how to properly cryopreserve MSCs. Basically, Trinity Evolution (in reality) is a VERY different product from the original Trinity because the original Trinity has ZERO viable MSC in the final product. I probably shouldn't discuss processing methods as those are highly under lock and key. But I can say they the Trinity Evo also has a higher BMP2/7 content than original Trinity, which of course = more osteoinductivity.

2. Infuse is contraindicated (by the FDA) for use in spinal fusion. Why, you may ask. Well it has already led to a few deaths. Infuse is an awesome product. BUT it's 1ml? of pure BMP2 on a collagen sponge (which is a poor matrix for retaining BMPs but nevertheless works). IT WILL OVERGROW and cause impingements. Look at what happened to Gov. Corezine (I'm probably misspelling his name) of NJ. He had Infuse in his leg and needed to have another surgery to correct the overgrowth.

I hope I provided some answers to people who really wanted to know.
Have fun.
 






The issue you all have is not seeing what is the next generation. Osiris now has developed both Grafix and Ovation which is chock for of LIVE, VIABLE Placenta (amnion/chorion) MSC's. This is the defacto winner in any of these debates. NOthing else has the combination of placental MSC's and being live and viable.

Their processing is second to none and the results are outstanding from diabetic, venous, arterial ulcers to burns and spinal fusions (Ovation).

I would educate you here but I'm having too much fun reading your back and forth! LOL.
 






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