Aaom april 2012 florida centenoPresentation Transcript
Financial Disclosures•I am a share holder and medicaldirector of Regenerative Sciences, LLC•I am not being directly compensatedfor this presentation
Intradiscal Stem cells: Are they an Effective Treatment Technique? Chris Centeno, M.D.
What autologous biologics can be used in discs?• Blood Products – PRP – Platelet lysates – Cultured serum (IRAP) – Cultured platelet supernatants• Stem cells – Bone marrow aspirate concentrate – Cultured stem cells
At one time or another, we’ve used all of these things in discs…• Blood Products – PRP – Platelet lysates – Cultured serum (IRAP) – Cultured platelet supernatants• Stem cells – Bone marrow aspirate concentrate – Cultured stem cells
How do we currently treat a disc bulge with surgery?
Is there a problem with trimming the outer disc? Less outer disc to hold annulus. Is it surprising that we get recurrent disc herniations?
What if we could rebuild thetorn fibers of the outer disc?
Are bipeds like quadrupeds?•Sakai. Biomaterials.2003 Sep;24(20):3531-4.•Able to regeneraterabbit IVD’s by injectingcultured bone marrowMSC’s = ?
Our research experience: (pre-post 3.0T MRI with pain functional ratings) •Injected concentrated bone marrow nucleated cells (BMAC) and PRP into NP-Didn’t work. •The next step? •Isolate and then culture expand MSC’s.10
So how do you isolate and growmesenchymal stem cells ex-vivo? Expand them by passaging into new flasks. They should double every 2 days.
Our research experience:(pre-post 3.0T MRI with pain functional ratings) •Injected culture expanded MSC’s into NP- Didn’t work. = ? 1 2
So what’s unique about human discs? •They have really poor blood supply past adolescence •They have unusually high loads •There is a stark difference between an animal stab model of DDD and the real McCoy13
So what’s unique about human discs? •They are hypoxic and acidic •They get their nutrition by primarily imbibition (pump like nutrient diffusion) and secondarily blood supply •In a DDD patient, the cells in the NP are like survivalists dropped in the middle of the Sahara desert14
For the last decade, some European researchers have postulated that DDD and radiculopathy are vascular problems…15
Disc Blood Supply16
If you place cells here, they have a blood supply and will surviveThese blood vesselsbecome incompetent,so the NP is avascular If you place cells here, they will not survive
Based on histology studies, there is a “red” area(vascularized) and a white area (poorlyVascularized) in the posterior disc annulus. 1 8
The problem is how do you physically get cells to this area via a needle?
What else besides placement can improve cell survival? •Increase vascular supply with vascular growth factors •Condition cells for low oxygen survival while still in culture21
The Results in Real Patients (not Rabbits)
Pre-procedure sagittal slice through 0.6 cm the maximum extent of the contained L4-L5 disc extrusion. Image was taken at 12:15 pm. ET=6, TR=4816.7, TE=48.1. The L4-L5 disc extrusion is measured at 0.6 cm. Disc heights measured at the mid-portion of the disc on this slice were: L4-L5=0.8 cm, L5- S1=0.7 cm, S1-S2=0.5 cm. 0.3 cm4.5 months post-procedure. Thisis matching sagittal STIR slice withsame imaging parameters. ET=6,TR=4833.3, TE=48.2. Image wastaken at 12:27 pm. The L4-L5 discextrusion is measured at 0.3 cm.Disc heights measured the sameas pre-procedure: L4-L5=0.8 cm,L5-S1=0.7 cm, S1-S2=0.5 cm.
Short Tau Inversion Recovery (STIR) image taken less than 1 month prior to procedure. This sagittal slice is chosen as it represents the maximum extent of the contained L5-S1 disc extrusion. 0.7 cm ET=6, TR=4816.7, TE=48.1 with an imaging time of day of 1:01 p.m. This image demonstrates a 0.7 cm disc extrusion at L5-S1. L5-S1 disc height measured at central disc is 0.5 cm with L4-L5 measuring at 0.7 cm.5 month post procedure matchingsagittal slice using the same STIRparameters. ET=6, TR=4816.7,TE=48.3. Imaging time of day was10:23 a.m. This image 0.3 cmdemonstrates a 0.3 cm discextrusion at L5-S1. Note discheights 0.5 cm at L5-S1 and 0.7 cmat L4-L5.
KG-39 year oldotherwisehealthy whitefemale statuspost a failedlaminectomy Before Afterdiscectomyfour years priorto injection ofMSC into herL5-S1 disc. Before After-Pre-op Jan 08 SagSTIR 3.0T MRI withET=12, TR=5550.0,TE=47.7Post-op Feb 09Sag STIR on samemagnet withET=12, TR=5550.0, AfterTE=47.4 Before
Before AfterKG-Axial T2 FRFSE scans on the same 3.0T scanner. Note the increased T2signal in the L5-S1 disc (brighter inside dashed circle) as well as theresolution of the right>left central disc bulge (red arrow).Pre-op Jan 08: ET: 19, TR: 3450.0, TE: 96.1Post op Feb 09: ET: 19, TR: 3450.0, TE:96.1
How about the same patient at 2 years?
How does this work?
Is there a way to manageradiculopathy and avoid the high dose steroids?
How about using platelets?• We have been substituting platelet lysate for corticosteroid in epidurals for about 3 years.• Our opinion is that it’s as good or better than steroids.• Tracking two large groups (PL vs. steroids) and should have that data by fall.
Regulatory Update• What’s the latest on whether FDA believes technologies are regulated as drugs? Exempt-Practice of Regulated as 351 Medicine Biologic Drug PRP Adipose SVF Bone Marrow Cultured Cells Concentrate
New Update: Adipose SVF is a Drug• FDA Tissue Reference Group has issued at least two letters showing that SVF is a new drug requiring clinical trials• The TRG has a special taskforce working on how to enforce this new initiative
Rodriguez FDA TRG LetterBreaking down the “adipose tissue” alters it’s relevant characteristics=Drug
Enforcement Actions on SVF• State of Florida Medical Board/Department of Health revoked the license of a cardiologist infusing IV SVF for pulmonary fibrosis after the patient died-Homicide Investigation in progress• State of Louisiana Medical Board has disallowed adipose SVF under the practice of medicine
On the flip side of the coin…• State of Texas Medical Board now allows “non- FDA Approved” stem cells to be used under the practice of medicine as long as: – The patient is consented as to the investigational nature of the care – The procedure is approved through an IRB
Summary• PRP and bone marrow concentrate don’t seem to help discs much• Routinely cultured stem cells placed into the NP don’t work well either• Specially cultured and administered stem cells do seem to be capable of resolving disc bulges• PRP and Bone Marrow Concentrates are being left alone by FDA, adipose SVF is the next big FDA enforcement target