1. Financial Disclosures
•I am a share holder and medical
director of Regenerative Sciences, LLC
•I am not being directly compensated
for this presentation

2. Intradiscal Stem cells: Are they an
Effective Treatment Technique?
Chris Centeno, M.D.

3. 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

4. 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

5. How do we currently treat a disc
bulge with surgery?

6. Is there a problem with trimming
the outer disc?
Less outer disc to hold
annulus. Is it
surprising that we get
recurrent disc
herniations?

7. What if we could rebuild the
torn fibers of the outer disc?

8. Disc
Regeneration
8

9. Are bipeds like quadrupeds?
•Sakai. Biomaterials.
2003 Sep;24(20):3531-4.
•Able to regenerate
rabbit IVD’s by injecting
cultured bone marrow
MSC’s
= ?

10. 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

11. So how do you isolate and grow
mesenchymal stem cells ex-vivo?
Expand them by passaging
into new flasks. They
should double every 2 days.

12. Our research experience:
(pre-post 3.0T MRI with pain functional
ratings)
•Injected culture expanded MSC’s into NP-
Didn’t work.
= ?
1
2

13. 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 McCoy
13

14. 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 desert
14

15. For the last decade, some European
researchers have postulated that DDD
and radiculopathy are vascular
problems…
15

16. Disc Blood Supply
16

17. If you place cells here,
they have a blood supply
and will survive
These blood vessels
become incompetent,
so the NP is avascular If you place cells here,
they will not survive

18. Based on histology studies, there is a “red” area
(vascularized) and a white area (poorly
Vascularized) in the posterior disc annulus.
1
8

19. The problem is how do you physically
get cells to this area via a needle?

20. Advances inner catheter Advances guide canula
Nitinol guide canula Nitinol inner catheter

21. What else besides placement
can improve cell survival?
•Increase vascular supply with
vascular growth factors
•Condition cells for low oxygen
survival while still in culture
21

22. The Results in Real Patients (not
Rabbits)

23. 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 cm
4.5 months post-procedure. This
is matching sagittal STIR slice with
same imaging parameters. ET=6,
TR=4833.3, TE=48.2. Image was
taken at 12:27 pm. The L4-L5 disc
extrusion is measured at 0.3 cm.
Disc heights measured the same
as pre-procedure: L4-L5=0.8 cm,
L5-S1=0.7 cm, S1-S2=0.5 cm.

24. 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 matching
sagittal slice using the same STIR
parameters. ET=6, TR=4816.7,
TE=48.3. Imaging time of day was
10:23 a.m. This image 0.3 cm
demonstrates a 0.3 cm disc
extrusion at L5-S1. Note disc
heights 0.5 cm at L5-S1 and 0.7 cm
at L4-L5.

25. KG-39 year old
otherwise
healthy white
female status
post a failed
laminectomy Before After
discectomy
four years prior
to injection of
MSC into her
L5-S1 disc.
Before After
-Pre-op Jan 08 Sag
STIR 3.0T MRI with
ET=12, TR=5550.0,
TE=47.7
Post-op Feb 09
Sag STIR on same
magnet with
ET=12, TR=5550.0, After
TE=47.4 Before

26. Before After
KG-Axial T2 FRFSE scans on the same 3.0T scanner. Note the increased T2
signal in the L5-S1 disc (brighter inside dashed circle) as well as the
resolution of the right>left central disc bulge (red arrow).
Pre-op Jan 08: ET: 19, TR: 3450.0, TE: 96.1
Post op Feb 09: ET: 19, TR: 3450.0, TE:96.1

27. How about the same patient at 2
years?

29. How does this work?

30. Is there a way to manage
radiculopathy and avoid the high dose
steroids?

31. 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.

32. 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

33. 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

34. Rodriguez FDA TRG Letter
Breaking down the “adipose tissue” alters it’s relevant characteristics=Drug

35. 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

36. 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

37. 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