disclosures regenerative medicine · marisa terry, md disclosures • neither i, marisa terry, nor...
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10/16/2017
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Regenerative Medicine
for the Spine
Health Care That Works
Andrews Research & Education Foundation
October 13, 2017Marisa Terry, MD
Disclosures
• Neither I, Marisa Terry, nor any family
member(s), have any relevant financial relationships to be discussed, directly or
indirectly, referred to or illustrated with or
without recognition within the presentation.
Learning Objectives
• Review non-operative regenerative medicine therapies that exist for spine pain
• Discuss current evidence supporting the use of non-operative regenerative medicine
interventions for spine pain
Standard Treatment Options
• Activity Modification
• Orthotics/Braces
• Physical Therapy
• Chiropractic Care, Acupuncture, Massage
• Pain Psychology Therapies
• Medications
• Injections
• Surgery
Regenerative Treatment
Options• Platelet-Rich Plasma (PRP)
• Bone Marrow derived Mesenchymal Stem Cells (SCs)
• Others not discussed today:– Prolotherapy (hyperosmolar dextrose)
– Lipoaspirate (adipose tissue-derived stem cells)
– Protein-based therapy (LMP-1, Fox C2, MMP-3, TIMP-1)
– Gene therapy via viral vectors (BMP-7, SOX-9, GDF-5, TGF-B3, CTGF, and TIMP1)
Platelet-Rich Plasma (PRP)
• What is it?
– Autologous blood derived product: plasma + platelets
– Concentrated platelets 2-8x above normal
• Platelet granules store growth factors (GFs) & cytokines
– Alpha granules store platelet-derived growth factors
which act in chondrocytes to:
– promote cartilage matrix synthesis
– increase cell growth & migration
– facilitate protein transcription
• Goal: targeted delivery of GFs directly at site of diseased tissue to stimulate the natural healing cascade & tissue regeneration
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Platelet-Rich Plasma (PRP)
• How is it prepared?
Mesenchymal Stem Cells
• MSCs are multipotent stromal cells (bone marrow, adipose
tissue, amniotic tissue) that can:
– act via paracrine mechanism, to produce growth factors, cytokines & trophic immune regulators (coordinate repair response, like prp)
– proliferate & differentiate into a variety of cell types: muscle, bone, cartilage, tendon, cells of internal organs (replace worn-out areas)
– in cartilage, MSCs may deactivate macrophages and secrete anabolic cytokines to halt cartilage breakdown
• Several animal studies show improvement of biomechanical properties, tissue architecture & functionality
– Restore disc height
– Improve extracellular matrix (upregulate anabolic gene expression and downregulate catabolic gene expression)
Mesenchymal Stem Cells:BMAC
Spine pain is Complex
Spine Pain
• Focus today:
– Lumbar Facet Joint
– Lumbar Disc
– Lumbar Radiculopathy
– Sacroiliac Joint
Spine Anatomy
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Spine Anatomy Lumbar Facet Joint
Lumbar Facet Joint
• PRP– Prospective trial of 19 patients for 3 months (Wu)
• Mean Visual Analog Scale VAS at rest decreased from 7 before treatment to 2.6 at 3 months.
• Mean Oswestry Disability Index ODI decreased from severe (17) & moderate (2) before treatment to moderate (19) after treatment.
• No adverse effects reported.
– Prospective trial of 14 patients for 6 months (Akeda)• Mean Numeric Rating Scale NRS pain score decreased from 7 to
1.8,
• Roland-Morris Disability Questionnaire scores (RDQ) decreased from 12.6 to 3.2, and
• MRI sagittal T2 maps showed no significant changes. • No major adverse effects reported.
• Stem Cells– No human trials identified
Lumbar Intervertebral Disc
Lumbar Intervertebral Disc• PRP
– Prospective trial of 22 patients for 6 months (Levi)• 63% pts had 20mm improvement in VAS
– 9 of 19 patients achieved a 50% improvement in VAS
• 47% pts had 30% improvement in ODI
• No adverse effects reported
– Prospective RCT of 21 patients, follow-up at 1 year (Tuakli)• Mean NRS improved by 2 points
• Mean Functional Rating Index (FRI) improved by 17 points
• Mean Short-Form-36 questionnaire (SF-36) improved by 24 points
• No adverse effects reported
• Stem Cells– Prospective trial of 26 patients for 2 years (Pettine)
• 21/26 pts avoided surgery. In those patients:
• VAS improved by 72%
• ODI improved by 67%
• MRI imaging: 20 pts had no change/ halted progression at 1 year.
• No serious complications reported
Lumbar Epidural
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Lumbar RadiculopathyEpidural injection for prolapsed disc causing radiculopathy
• PRP– Prospective trial of 10 patients for 3 months – ILESI
(Bhatia)• Mean VAS improved from 6.1 to 3.7
• Mean MODI improved from 49.2% (severe disability) to 29.5% (moderate disability)
• No complications reported
– Case series of 30 patients - Caudal or TFESI (Aufiero)
• 10 patients had few hours of pain relief
• 10 patients had 6wks-6months pain relief
• 10 patients had 8+ months pain relief
• Stem Cells– No human trials identified
Sacroiliac Joint
Sacroiliac Joint
• PRP
– Prospective randomized trial of 40 patients (either steroid or PRP) with ultrasound-guidance
for 3 months (Singla)• Mean VAS improved: PRP (7.5 to 1), Steroid (6 to 5)
• Mean MODI improved: PRP (42 to 15), Steroid (44 to 24)– Approximation as best interpreted from graph presented in article
• No serious adverse effects
• Stem Cells
– No human trials identified
Take Home Points
• Utility of regenerative medicine (PRP & SCs) therapies for chronic spine pain is in its infancy –limited available evidence, but…
• appears promising & safe, • offers an exciting alternative to
recalcitrant spine pain conditions
Current Challenges
• Lack of methadology standardization
• Consistency and volume of PRP or SCs
• Diagnostic criteria
– physical exam unreliable, painful provocative
tests
• Studies have shown a negative effect of PRP
and SC function when co-cultured with anesthetics, antibiotics, and contrast medium
– All these agents are commonly used during spine interventional procedures
References
• Wu, J., Du, Z., Lv, Y., Zhang, J., Xiong, W., Wang, R., ... & Liu, Q. (2016). A new technique for the treatment of lumbar facet joint syndrome using intra-articular injection with autologous platelet rich plasma. Pain physician, 19(8), 617-25.
• Obata, S., Akeda, K. Morimoto, R., Asanuma, Y., Kasai, Y., Masuda, K., … & Sudo, A. (2010, October). Intradiscal injection of autologous platelet-rich plasma – serum induces the restoration of disc height in the rabbit anular needle puncture model: 12. In Spine Journal Meeting Abstracts (p. 12). LWW.
• Bhatia, R., & Chopra, G. (2016). Efficacy of Platelet Rich Plasma via Lumbar Epidural Route in Chronic Prolapsed Intervertebral Disc Patients-A Pilot Study. Journal of clinical and diagnostic research: JCDR, 10(9), UC05.
• Singla, V., Batra, Y. K., Bharti, N., Goni, V. G., & Marwaha, N. (2017). Steroid vs. Platelet‐Rich Plasma in Ultrasound‐Guided Sacroiliac Joint Injection for Chronic Low Back Pain. Pain Practice, 17(6), 782-791.
• Levi, D., Horn, S., Tyszko, S., Levin, J., Hecht-Leavitt, C., & Walko, E. (2015). Intradiscal platelet-rich plasma injection for chronic discogenic low back pain: preliminary results from a prospective trial. Pain Medicine, 17(6), 1010-1022.
• Navani, A., Ambach, M. A., Wei, J. J., & Gupta, D. (2017). Biologic Therapies for Intervertebral Degenerative Disc Disease: A Review of Novel Applications. J Stem Cells Res. Rev & Rep, 4(1), 1023.
• Tuakli-Wosornu, Y. A., Terry, A., Boachie-Adjei, K., Harrison, J. R., Gribbin, C. K., LaSalle, E. E., ... & Lutz, G. E. (2016). Lumbar intradiskal platelet-rich plasma (PRP) injections: a prospective, double-blind, randomized controlled study. PM&R, 8(1), 1-10.
• Pettine, K., Suzuki, R., Sand, T., & Murphy, M. (2016). Treatment of discogenic back pain with autologous bone marrow concentrate injection with minimum two year follow-up. International orthopaedics, 40(1), 135-140.
• Aufiero, D., Vincent, H., Sampson, S., & Bodor, M. (2015). Regenerative injection treatment in the spine: review and case series with platelet rich plasma. J Stem Cells Res. Rev & Rep, 2(1), 1019.
