Biologic disc treatments

[wilsonrob]

Don't forget The Regenexx? Procedure
Dramatic Reduction in Disc Bulge with Disc Stem Cell Injection
LM is a 39 year old male with a 16 year history of severe low back and leg pain. He underwent injection of his own cultured stem cells into his disc bulge. His bulge was very large, so he barely met the study criteria and frankly I wasn’t optimistic about his possibilities, but he was entered into the study largely on the optimism of my partner, Dr. Schultz. Well, LM proved me wrong this week. He is now 7 months post procedure and is 80% better. His films are above. Note the very large disc bulge at the tip of the red arrow on both the before images (top is a saw you in half axial view, bottom left is a side view sagittal). Then note the marked reduction in the size of the disc bulge seen at the tip of the yellow arrow in both matching slices on the right. I have also highlighted the S1 nerve on the axial films (the before and after on the top)-red dot on the before, yellow dot on the left. Note how the disc was pressing on this nerve in the before image and is now far away from the disc in the after. This also corresponds to a reduction in his leg symptoms related to this S1 nerve. Realize all of this was accomplished with only an injection and without surgery. Since this disc bulge had been there for a long time and was worsening before treatment, it’s unlikely this represents spontaneous resolution of this disc.

[BPrice]

Here is info on fibrin injections. This info came from Spine Journal published proceedings (2009; 10S:105S) that are mentioned on the SpinalRestoration website:

This study used pig lumbar spines. To damage the discs, a 19G needle was used to remove 1 ml of nucleus material.

"Nucleotomy produced transient increases in IL-6 and TNF- at 3 weeks that were prevented by fibrin injection. For the no-treatment and fibrin-treated discs, stiffness and leakage pressure were less than control at 3 weeks. Stiffness returned to normal at 6 weeks for the fibrin-treated levels and at 12 weeks for the no-treatment levels. Disc proteoglycan content was less than controls at 3 and 6 weeks for the no-treatment and fibrin-treated levels. GAG content returned to normal at 12 weeks for the fibrin-treated levels, but not for degenerate discs. No adverse cellular reaction to fibrin injection was noted by histology."

I wonder how much less proteoglycan content was in the fibrin-treated levels, and I wonder how the fibrin treatment would fare against a torn disc (as the website states, Biostat "occludes annular fissures"). I don't believe such a claim can be substantiated by this trial.

The SpinalRestoration website mentions an unpublished document named "Fibrin sealant modulates the inflammatory response in intervertebral disc cells." If anyone can find this or any good info on this mode of treatment, please let me know. Thanks.

[Crystal33]

BPrice,
Regarding fibrin, i had no luck finding a copy of ......."3 Buser Z, Jane L, Thorne KJ, et al. Fibrin sealant modulates the inflammatory response in intervertebral disc cells. Unpublished manuscript."
Being "unpublished" is likely reason.

Found this promising paper....
J Biomater Sci Polym Ed. 2008;19(9):1219-37.
Fibrin promotes proliferation and matrix production of intervertebral disc cells cultured in three-dimensional poly(lactic-co-glycolic acid) scaffold.

Sha'ban M, Yoon SJ, Ko YK, Ha HJ, Kim SH, So JW, Idrus RB, Khang G.

Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, Malaysia.
Abstract

Previously, we have proven that fibrin and poly(lactic-co-glycolic acid) (PLGA) scaffolds facilitate cell proliferation, matrix production and early chondrogenesis of rabbit articular chondrocytes in in vitro and in vivo experiments. In this study, we evaluated the potential of fibrin/PLGA scaffold for intervertebral disc (IVD) tissue engineering using annulus fibrosus (AF) and nucleus pulposus (NP) cells in relation to potential clinical application. PLGA scaffolds were soaked in cells-fibrin suspension and polymerized by dropping thrombin-sodium chloride (CaCl(2)) solution. A PLGA-cell complex without fibrin was used as control. Higher cellular proliferation activity was observed in fibrin/PLGA-seeded AF and NP cells at each time point of 3, 7, 14 and 7 days using the MTT assay. After 3 weeks in vitro incubation, fibrin/PLGA exhibited a firmer gross morphology than PLGA groups. A significant cartilaginous tissue formation was observed in fibrin/PLGA, as proven by the development of cells cluster of various sizes and three-dimensional (3D) cartilaginous histoarchitecture and the presence of proteoglycan-rich matrix and glycosaminoglycan (GAG). The sGAG production measured by 1,9-dimethylmethylene blue (DMMB) assay revealed greater sGAG production in fibrin/PLGA than PLGA group. Immunohistochemical analyses showed expressions of collagen type II, aggrecan core protein and collagen type I genes throughout in vitro culture in both fibrin/PLGA and PLGA.

In conclusion, fibrin promotes cell proliferation, stable in vitro tissue morphology, superior cartilaginous tissue formation and sGAG production of AF and NP cells cultured in PLGA scaffold. The 3D porous PLGA scaffold-cell complexes using fibrin can provide a vehicle for delivery of cells to regenerate tissue-engineered IVD tissue....."


A broader study.... The implantation of non-cell-based materials to prevent the recurrent disc herniation: an in vivo porcine model using quantitative discomanometry examination

Small numbers of spine patients have actually had Fibrin disc treatment and a few have posted their outcomes on the web. 'Sounds' incredible actually. Is a pity medical industry or big pharma didn't put some serious money into biological disc treatment research years ago. Maximum $ per patient seems to be their focus.
I edited names.

" 18 January, 2010. I just had my second 4 level Fibrin Sealant last week. My first treatment was 4 level also in October of 2008. Before learning of the Fibrin Sealant I was told by every surgeon I saw in Honolulu I needed 3 level fusion. I looked into the ADR option , but was told since I would need 2 level high on the lumbar L2-3 L3-4 my chances would be poor at best. I then read .......'s post about her Fibrin Sealant she had in Tyler Texas. The idea of not having hardware in my spine and life without pain meds was worth a shot, no pun intended. I came to Texas with very bad leg pain before my first treatment and a constant stabbing pain on my left facet joint besides disc pain. I walked out of the first treatment without any leg pain period and most of the facet and disc pain was much better.

After 5 weeks I was completely pain free and off all pain meds. The relief lasted over 12 months but slowly crept back except the leg pain which has remained pain free. I decided to have a second treatment in Texas again, once again my disc pain and facet pain has disappeared. Anyone who wants a less invasive treatment should consider the Fibrin Sealant. It burns no bridges and might bring long lasting pain relief. Time and technology will always improve your chances for a better treatment.

Aloha ...........____________
Surfing Accident 20 years ago.
Back pain started 3 to 4 years ago.
Chiropractics, Massage, Meds
MRI 7/30/07
MRI 8/1/08
MRI 3/1/09
DDD in L2-3 and L3-4
Facet injections almost every month for 16 months
Discogram 9/1/08 Positive L2-3 L3-4
4 Level Fibrin Sealant 10/08 pain relief to my legs the next day. Disc Pain much better , but pain returning about 8/09.
4 Level Fibrin Sealant top off 1/10 looking forward to a longer relief this time. "

"21 January, 2010.
Yes the study is very limited and full at this point, but you might be able it receive fibrin sealant outside of the study. Remember I was turned down by all the ADR surgeons based on how many levels I needed and the levels on the lumbar spine. I went from daily goofballs Vicoden ES to no pain meds within 5 weeks of my first procedure and I had 4 levels done. So going from almost inoperable, besides fusion, to pain free and med free with in less then 6 weeks. Without this procedure I would have a 3 level fusion right now and even thou I needed a second treatment I am planning a surf trip to Sumatra Indonesia in April and enjoyed surfing in Hawaii all summer last year.

If I had to get topped off with additional injections for the rest of my life it would be well worth the quality of life it gave me back. With all the technology that will improve the current ADR think how much a few years time a fibrin injection could give you time to get a much better ADR down the road a few years and maybe you will be able to avoid the hardware completely.

Cheers .............
_______________
Surfing Accident 20 years ago.
Back pain started 3 to 4 years ago.
Chiropractics, Massage, Meds
MRI 7/30/07
MRI 8/1/08
MRI 3/1/09
DDD in L2-3 and L3-4
Facet injections almost every month for 16 months
Discogram 9/1/08 Positive L2-3 L3-4
4 Level Fibrin Sealant 10/08 pain relief to my legs the next day. Disc Pain much better , but pain returning about 8/09.
4 Level Fibrin Sealant top off 1/10 looking forward to a longer relief this time."

[Crystal33]

I should add link about fibrin Phase III clinical trial. They appear to very serious about their product.
Newsroom - Spinal Restoration
http://www.lowbackstudy.com/

[Crystal33]

BPrice,
Another post i found regarding fibrin disc injection, by a girl with major spine history.
When this type of treatment hits the market it will worry and then force major companies to compete in this area, leading to more advances. a long overdue option for some, between conservative care and major surgery.

01-20-2009, 11:37 AM
XXXXXXXXX
Senior Member

One thing everyone needs to understand is that my spine is more screwed up than the average bear. I have had 6 spinal surgeries and my lumbar artificial disks are in wrong. This is causing scoliosis and the way they are placed continually puts more load on my other disks. This is why I need another sealant done. Most people have gotten at least 3 years out of the injection and are doing well. 3 years is as long as it has been in anyone. I believe 80% have gotten long-term relief. I would not get discouraged that I need another sealant done. I don't think I am the ideal candidate to rate Fibrin on because of the malplacement of my artificial disks. It does work so well that I am willing to give it another try. It is a lot better than taking your chances with a major surgery that may or may not work.
Sincerely,
__________________
XXXXXXXXX

10-02 - ProDiscs L4/5 and L5/S1 - FDA study - disks placed incorrectly which
caused problem at L3/4 and L2/3
01-05 - ProDiscs at C5/6 and C6/7 in Germany - seems to be working fine so far
Bedbound from 09-06 until 10-08 due to severe pain and weakness
09-08 - Had Fibrin sealant done at L3/4 and L2/3 After 6 weeks - much success!
Hoping and praying that the lumbar revision surgery that was scheduled with Dr. Regan
can be indefinitely postponed

[lugar]

Cells and Biomaterials for ... - Google Libros

[mmglobal]

Lugar,

Welcome to the forum! Thanks for posting.

LM is an unnamed participant in the study that was being published by the Regenex people. They had a facility in Colorado that had some diffuculty in the past and had stopped doing their procedures. I don't know if they started again.. Rob... do you have an update?

Dr. Bertagnoli in Germany is still doing the ADCT (atologous chondrocyte) harvesting and reimplantation procedure. You can contact his staff directly or if you'd like some help with the presentation, let me know (via the GPN website linked below.)

[lugar]

Thanks for you answer. I thought Dr. Bertagnoli was specialist in disc replacement and that condrocytes treatment was actually in Codon clinic, but I thought too that they had stopped. I wrote to them, but I got no answer; maybe I should try again.

As I said, I received the stem cell treatment, so I will tell you if it works or not.

Thank you again.

Lugar

[Crystal33]

You never know if what u read on the web is fact or fiction. The following post I found elsewhere, sounded almost too good to be true. But I found a scientific extract recently (bottom) that gives it a lot of credibility.

I then did a Pubmed search under "intervertebral disc regeneration" and discovered that a lot of impressive research and testing has taken place over recent years. There would probably be mainstream biologic treatments happening today except that surgeons and medical industry have been (and will remain) much more motivated by the huge profit levels made from surgery as well as the metal bits and pieces that cost thousands.


extract of post...."I was turned down by all the ADR surgeons based on how many levels I needed and the levels on the lumbar spine. I went from daily goofballs Vicoden ES to no pain meds within 5 weeks of my first procedure and I had 4 levels done. So going from almost inoperable, besides fusion, to pain free and med free with in less then 6 weeks. Without this procedure I would have a 3 level fusion right now and even thou I needed a second treatment I am planning a surf trip to Sumatra Indonesia in April and enjoyed surfing in Hawaii all summer last year."


J Biomater Sci Polym Ed. 2008;19(9):1219-37.
Fibrin promotes proliferation and matrix production of intervertebral disc cells cultured in three-dimensional poly(lactic-co-glycolic acid) scaffold.

Sha'ban M, Yoon SJ, Ko YK, Ha HJ, Kim SH, So JW, Idrus RB, Khang G.

Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, Malaysia.
Abstract

Previously, we have proven that fibrin and poly(lactic-co-glycolic acid) (PLGA) scaffolds facilitate cell proliferation, matrix production and early chondrogenesis of rabbit articular chondrocytes in in vitro and in vivo experiments. In this study, we evaluated the potential of fibrin/PLGA scaffold for intervertebral disc (IVD) tissue engineering using annulus fibrosus (AF) and nucleus pulposus (NP) cells in relation to potential clinical application. PLGA scaffolds were soaked in cells-fibrin suspension and polymerized by dropping thrombin-sodium chloride (CaCl(2)) solution. A PLGA-cell complex without fibrin was used as control. Higher cellular proliferation activity was observed in fibrin/PLGA-seeded AF and NP cells at each time point of 3, 7, 14 and 7 days using the MTT assay. After 3 weeks in vitro incubation, fibrin/PLGA exhibited a firmer gross morphology than PLGA groups. A significant cartilaginous tissue formation was observed in fibrin/PLGA, as proven by the development of cells cluster of various sizes and three-dimensional (3D) cartilaginous histoarchitecture and the presence of proteoglycan-rich matrix and glycosaminoglycan (GAG). The sGAG production measured by 1,9-dimethylmethylene blue (DMMB) assay revealed greater sGAG production in fibrin/PLGA than PLGA group. Immunohistochemical analyses showed expressions of collagen type II, aggrecan core protein and collagen type I genes throughout in vitro culture in both fibrin/PLGA and PLGA. In conclusion, fibrin promotes cell proliferation, stable in vitro tissue morphology, superior cartilaginous tissue formation and sGAG production of AF and NP cells cultured in PLGA scaffold. The 3D porous PLGA scaffold-cell complexes using fibrin can provide a vehicle for delivery of cells to regenerate tissue-engineered IVD tissue.

[Crystal33]

Some recent biologic disc treatment outcomes........


Intervertebral disc regeneration after implantation of a cell-free bioresorbable implant in a rabbit disc degeneration model.
Department of Rheumatology, Tissue Engineering Laboratory, Charité-Universitätsmedizin Berlin, Germany; TransTissue Technologies GmbH, D-10117, Berlin, Germany.

Source Biomaterials 2010 Apr 27.

Abstract Degeneration of the intervertebral disc is the most common cause of lower back pain. Interestingly, all available treatments are limited to treat the symptoms and not the underlying biologic alterations of the disc. Freeze-dried resorbable non-woven polyglycolic acid (PGA) - hyaluronan implants were used in a degenerated disc disease (DDD) model in New Zealand white rabbits. The constructs were immersed in allogenic serum and implanted into the disc defect. Animals with discectomy only served as controls. The T2-weighted/fat suppression sequence signal intensity of the operated discs as assessed by magnet resonance imaging decreased in both groups one week after the operation compared to a healthy disc. After 12 months the implanted group showed an increase of 51% in the signal intensity compared to the 1-week results whereas the signal intensity in the sham group remained on the same level from one week to 12 months. Histological and quantitative immunohistochemical examination after 12 months indicated cell migration into the defect and showed formation of disc repair tissue.

In controls, repair tissue containing type II collagen was not evident.
In conclusion, the implantation of polymer-based constructs after discectomy induces tissue regeneration resulting in improvement of the disc water content.

00000000000000000000000000000000000000000000000000 0000000000000000000

Disc Regeneration Therapy Using Marrow Mesenchymal Cell Transplantation: A Report of Two Case Studies.

Department of Orthopaedic Surgery, Nara Medical University, Nara, Japan.
2010 Apr 23.

STUDY DESIGN.: Marrow mesenchymal cells (MSCs) contain stem cells and possess the ability to regenerate bone, cartilage, and fibrous tissues. Here, we applied this regenerative ability to intervertebral disc regeneration therapy in an attempt to develop a new spinal surgery technique.

OBJECTIVE.: We analyzed the regenerative restoration ability of autologous MSCs in the markedly degenerated intervertebral discs.

SUMMARY OF BACKGROUND DATA.: Fusion for lumbar intervertebral disc instability improves lumbago. However, fused intervertebral discs lack the natural and physiologic functions of intervertebral discs. If intervertebral discs can be regenerated and repaired, then damage to adjacent intervertebral discs can be avoided. We verified the regenerative ability of MSCs by animal studies, and for the first time, performed therapeutic intervertebral disc regeneration therapy in patients and obtained favorable findings.

METHODS.: Subjects were 2 women aged 70 and 67 years; both patients had lumbago, leg pain, and numbness. Myelography and magnetic resonance imaging showed lumbar spinal canal stenosis, and radiograph confirmed the vacuum phenomenon with instability. From the ilium of each patient, marrow fluid was collected, and MSCs were cultured using the medium containing autogenous serum. In surgery, fenestration was performed on the stenosed spinal canal and then pieces of collagen sponge containing autologous MSCs were grafted percutaneously to degenerated intervertebral discs.

RESULTS.: At 2 years after surgery, radiograph and computed tomography showed improvements in the vacuum phenomenon in both patients. On T2-weighted magnetic resonance imaging, signal intensity of intervertebral discs with cell grafts was high, thus indicating high moisture contents. Roentgenkymography showed that lumbar disc instability improved. Symptom was alleviated in both patients.

CONCLUSION.: The intervertebral disc regeneration therapy using MSC brought about favorable results in these 2 cases. It seems to be a promising minimally invasive treatment.

[Crystal33]

A single injection promotes disc Regeneration

Hard to get medical industry to run with these treatments, when the huge money is to be made in ADR and fusion hardware.

CONCLUSION: The results of this study show the feasibility of restoring degenerative rabbit discs by a single injection of OP-1 into the nucleus pulposus. Importantly, the effects of the OP-1 injection on disc height were sustained for up to 24 weeks. The metabolic changes in the cells, following a single injection, might be sustained and, thus, induce long-term changes in disc structure. An efficacy study in large animals is required to show further that the intradiscal injection of OP-1, or bone morphogenetic proteins or growth factors with similar properties would be useful for the structural restoration of the IVD in humans.

Osteogenic protein-1 injection into a degenerated ... [Spine (Phila Pa 1976). 2006] - PubMed result

[Crystal33]

Red wine for disc degeneration.......

The Action of Resveratrol, a Phytoestrogen Found in Grapes,... : Spine

[Crystal33]

Have to add collagen type II to the list. A few human and numerous animal studies have shown that it significantly reduces joint pain. Combined with Glucosamine & Chondroitin seems to be superior to either alone.
It's something else that is not really heard about because there's no money in it to attract attention of big pharma or medical industry.
Could be worth a try for pain reduction. The following product sounds good, but i can't speak from experience.
ImmuCell Kolla2 Collagen Type ll 600mg 120 Capsules by Neocell Laboratories - $24.99

[lugar]

Hello,

The first thing I must do is apologise for my bad english. I am in Madrid and I have suffered from low back pain for two years. I have intervertebral disc degeneration in L5-S1. I had a treatement with my own cultured stem cells on June 2010. My back and leg pain has improved about 40%, maybe a little more, but I have still problems. My question is about where is possible to get this kind of treatments. For example, where LM did he get it? Do you know which clinics in Europe are doing the treatments? And do you know if they are getting good results?

Thank you. You can ask everything about my treatment if it interests you.

Luis

Originally Posted by wilsonrob

Don't forget The Regenexx? Procedure
Dramatic Reduction in Disc Bulge with Disc Stem Cell Injection
LM is a 39 year old male with a 16 year history of severe low back and leg pain. He underwent injection of his own cultured stem cells into his disc bulge. His bulge was very large, so he barely met the study criteria and frankly I wasn’t optimistic about his possibilities, but he was entered into the study largely on the optimism of my partner, Dr. Schultz. Well, LM proved me wrong this week. He is now 7 months post procedure and is 80% better. His films are above. Note the very large disc bulge at the tip of the red arrow on both the before images (top is a saw you in half axial view, bottom left is a side view sagittal). Then note the marked reduction in the size of the disc bulge seen at the tip of the yellow arrow in both matching slices on the right. I have also highlighted the S1 nerve on the axial films (the before and after on the top)-red dot on the before, yellow dot on the left. Note how the disc was pressing on this nerve in the before image and is now far away from the disc in the after. This also corresponds to a reduction in his leg symptoms related to this S1 nerve. Realize all of this was accomplished with only an injection and without surgery. Since this disc bulge had been there for a long time and was worsening before treatment, it’s unlikely this represents spontaneous resolution of this disc.