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TOPIC: Knees Microfracture results underwhelming

Knees Microfracture results underwhelming 29 Nov 2014 09:27 #2818

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The standard of care for knee issues (there are many different types of problems, but generally here, damaged cartilage tissue is assumed) tend to be "Microfracture". This is where a surgeon -during arthroscopy- simply punches some more holes in the cartilage, I presume to attract endogeneous cells in the hope that they repair the newly created holes AND the damaged cartilage.

Chris Centeno- who obviously is a specialist in this field- tweeted about an article on his Regenexx page, with a link to the study and his own comments, which were as follows:

Does microfracture surgery work? You might be surprised to learn that we still don’t know via high level research that micro fracture is more effective than doing nothing. In addition, we know even less about the long-term effects of the surgery. This is why a recent study is important. The researchers looked at 110 patients who had knee microfracture surgery and followed them for an average of 12 years after the procedure. Over 1/3 of the patients needed additional knee surgeries and almost half had a poor outcome from microfracture. Perhaps the author’s own conclusion sums up best what they found: “a normal knee function was generally not achieved, and many patients had further surgery. The results call for more research and, at present, caution in recommending microfracture in articular cartilage defects, especially in subgroups with worse prognosis.” Who had a worse prognosis? Anyone with any type of arthritis or meniscus tear.
The upshot? The long-term knee microfracture results aren’t good. In addition, the added invasiveness of the surgery (poking many holes in the bone) and added downtime (many weeks on crutches), don’t seem to be be matched by good enough long-term results for the authors of this paper to recommend the surgery in most patients.


The study he referred to : PubMed publication

Centeno´s full article : Regenexx article

Going forward, you will read a lot about Chris Centeno being highly sceptical about using fat cells for orthopedic purposes- be it in cartilage or in bone. :grin: I do not think that is correct- BM and fat cells react different in their biochemistry, but the triggering is the key issue going forward, I believe.

As usual - Time will tell. :cool:
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Knees Microfracture results underwhelming 29 Nov 2014 12:27 #2820

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For Cytori... its future ...and its survival... the next steps will be very important and have to be right, because so many chances have been ruined by bad management in the past 10 years.

Personally I slowly am getting comfortable with OA and (asap as FDA agrees) Scleroderma of the hands, as first steps on the US market to get "device equivalent Phase II data" for i.e pilot device clinics in the US.

Of course Japan will lead the way and hopefully bring the money to be able to afford that. We will know soon enough if that is feasible. :write: :whistle:

But just to get more comfortable- why not re-visit the teachings of Arnold Caplan. This person knows and can explain scientifically what Cytori has NOT been able to do in the past 10 years.... :cry: :cry:

So lets call Arnie again.. :woohoo:

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Knees Microfracture results underwhelming 29 Nov 2014 13:59 #2822

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Reason for turning to Arnold Caplan is obvious... at Case Western



he leads the "Skeletal Research Centre" i.e. next to be "the" expert on MSCs, also is a leading researcher in the orthopedic world of MSCs.

This will bring us to "new" organisations like the International Cartilage Repair Society (ICRS) and such things..



The times they are a changin´
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Knees Microfracture results underwhelming 02 Dec 2014 11:32 #2828

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I have spent quite some time reading up on OA and the science related to it together with the medical challenges, which have been casting some doubt again on the feasibility of the application and the question whether ADRCs are really the right cell type for it. :whistle:

Without ado but with further explanation on the thought processes,let us start with Caplan and take note what he has written about what MSCs have done with effectively becoming "hyaline articular cartilage" (i.e. the type thats in our knees) and the first impression is not favorable at all.... :yawn:

The paper that came out in 2013 you will find attached and here only the conclusion of the paper:

The main challenges that remain with MSC-based articular cartilage TE, such as quality and durability of the de novo generated tissue, its resistance to an endochondral ossification program, and its effective integration into the anatomic-specific host tissue, may be due to the intrinsic inability of MSCs to differentiate into articular cartilage or may be a reflection of our poor understanding of the underlying MSC biology.
MSCs can be isolated from many human vascularized tissues as they reside as perivascular cells, including various locations within the joint that may be considered as potential reservoir of chondroprogenitor cells. Until now exogenously administered as well as endogenously mobilized MSCs have failed to contribute to durable and phenotypically correct (i.e., anatomic sitespecific) articular cartilage regeneration, observations that might cast doubt on the usefulness of MSCs in regeneration of hyaline articular cartilage. This apparent lack in potential of MSCs to give rise to stable cartilage may come from restrictions imposed during embryonic development. Therefore, it is possible that their functions and responses in developing tissues are quite different from adult tissues.
ESC and iPSC technology have provided evidence that these restrictions may be circumvented, which would allow us to obtain cells with an intrinsic potential to regenerate sitespecific articular cartilage. Whether adult marrow MSCs are suitable for such sitespecific articular cartilage TE or have an intrinsic endochondral bone formation program is still an open question, but the latter seems likely. Moreover, whether adult MSCs have lost their intrinsic ability to differentiate into articular cartilage or whether we are not currently able to recreate the developmental milieu to which they are exposed during embryology are also unanswered and challenging questions.

We suggest that, at the very least, regenerating stable articular cartilage using MSCs will require us to implement more rigorous methodologies to precisely mimic morphogenetic
events of embryonic development of cartilage, yet note that more information as to how this process successfully guides stem cells to differentiate into a cartilage phenotype is still needed.



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Knees Microfracture results underwhelming 04 Dec 2014 13:45 #2840

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Hey FAS...... why do you think VETSTEM is so successful in treating animals with osteoarthritis?

Its the same procedure and methodology, no? You would think the results in humans would mirror those in dogs?

Or maybe its just that VETSTEM treats regular arthritis. Even if its regular arthritis, you'd think that Cytori could utilize all of VETSTEM's real world knowledge to streamline a human test. Arthritis in humans has to be very lucrative.

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Knees Microfracture results underwhelming 05 Dec 2014 08:34 #2848

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Or maybe its just that VETSTEM treats regular arthritis. Even if its regular arthritis, you'd think that Cytori could utilize all of VETSTEM's real world knowledge to streamline a human test. Arthritis in humans has to be very lucrative.


Hi CD-

I think you have a point. The data from Centeno and Cellthera dealt with reduction of pain and becoming "mobile" again, which last impact also applied to the animals treated by VetStem.

I dont know- there are a few new developments, which we will have to keep an eye on.

by the way- you really do not have the looks of a CC Doppelgänger- you look very much like the original version. :winky:

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Knees Microfracture results underwhelming 05 Dec 2014 09:04 #2849

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Fas,

I think you will be interested in this clinical trial that is using microfracture, with ADRCs and, in comparison without them. The technology is a tabletop EU approved processor by Texas based Ingeneron. They have also had success treating animals. clinicaltrials.gov/show/NCT01799876

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Knees Microfracture results underwhelming 05 Dec 2014 09:29 #2850

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Fas,

There is evidence that ADRCs work for osteoarthritis despite Dr. Centeno's position. When I was having problems with my knee I did much research. This was the most promising report I found and it includes MRI evidence. One important aspect is that it also included a scaffold: www.ncbi.nlm.nih.gov/pmc/articles/PMC3154169/ . Its only a handful of patients but the results are impressive.
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Knees Microfracture results underwhelming 05 Dec 2014 09:39 #2851

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Fas,

If you haven't read this , you will want to.

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Knees Microfracture results underwhelming 05 Dec 2014 10:06 #2852

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Wall Street Titan wrote: Fas,

I think you will be interested in this clinical trial that is using microfracture, with ADRCs and, in comparison without them. The technology is a tabletop EU approved processor by Texas based Ingeneron. They have also had success treating animals. clinicaltrials.gov/show/NCT01799876





While i certainly laud competitors spending their cash to promote Cytori's intellectual property, in the long run this patent infringement really unnerves me. (moat or no moat).

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Knees Microfracture results underwhelming 05 Dec 2014 11:33 #2853

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Yes- all interesting and relevant information.

There is something funny with InGeneron- on their website they show a small image of the Transpose RT system for clinical use-

here- Transpose RT System

They are however pulling our leg- I found a blown up version of that image and in actual fact they show the PRP device... :grin: :grin:





maybe they are simply using the TissueGenesis device... :whistle:
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Knees Microfracture results underwhelming 05 Dec 2014 11:58 #2855

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Wow- that paper from John Anderson did all the work for us. Great stuff- will study that a bit more. :yep:

Did you guys know we all have a fat pad in our knees? Well I did not- but than again knee problems is no issue here.



Anderson didnt however have the Stanford study that compares microfracture with prp and fat cells. That one is quite recent though.

Stanford study on OA

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Knees Microfracture results underwhelming 08 Dec 2014 06:40 #2862

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If you look at images like the last one of a knee, you realize that its not just the bone and cartilage which can create issues and pain, but the whole tissue matrix, including tendons and muscles.

One of the tweets of today (which you find on the right side of the "recent" and "index" pages of the lodge), pointed to a paper from the Leipzig University who checked the MSCs from different sources of the body for gene expression.

Background: Multipotent mesenchymal stromal cells (MSC) can be recovered from a variety of tissues in the body.
Yet, their functional properties were shown to vary depending on tissue origin. While MSC have emerged as a favoured cell type for tendon regenerative therapies, very little is known about the influence of the MSC source on their properties relevant to tendon regeneration. The aim of this study was to assess and compare the expression of tendon extracellular matrix proteins and tendon differentiation markers in MSC derived from different sources as well as in native tendon tissue. MSC isolated from equine bone marrow, adipose tissue, umbilical cord tissue, umbilical cord blood and tendon tissue were characterized and then subjected to mRNA analysis by real-time polymerase chain reaction.
Results: MSC derived from adipose tissue displayed the highest expression of collagen 1A2, collagen 3A1 and decorin compared to MSC from all other sources and native tendon tissue (p < 0.01). Tenascin-C and scleraxis expressions were highest in MSC derived from cord blood compared to MSC derived from other sources, though both tenascin-C and scleraxis were expressed at significantly lower levels in all MSC compared to native tendon tissue (p < 0.01).
Conclusions: These findings demonstrate that the MSC source impacts the cell properties relevant to tendon regeneration. Adipose derived MSC might be superior regarding their potential to positively influence tendon matrix reorganization.


Good that we have this confirmed... :cool:

The whole paper you can find here too....

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Knees Microfracture results underwhelming 08 Dec 2014 09:33 #2863

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Fas, I figured you'd appreciate that study. Could you send me a link to the study on baldness. I'm curious as to how the ADRCs were administered and, of course, the results.

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Knees Microfracture results underwhelming 08 Dec 2014 10:08 #2864

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Ray- I only have the piece that they published in the IFATS book- which was pre-lim for 9 patients

I also copied and pasted that on the lodge board.

Board entry on Alocepia

If you want more info- just mail Kerastem and ask the guys. Eric Daniels is pretty open.

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