Regenerative Treatment of Spinal Conditions

Transcription

1 Regenerative Treatment of Spinal Conditions Gerard A. Malanga, MD Kessler Institute Regenerative Medicine New Jersey Sports Medicine, LLC New Jersey Regenerative Institute Clinical Professor, Department of PM&R Rutgers School of Medicine

2 Diclosures Editor, textbook: Musculoskeletal Physical Examination: An Evidence-Based Approach Atlas of Ultrasound-Guided Musculoskeletal Injections; Regenerative Treatments in Sports and Orthopedic Medicine Consultant: Lipogems PRP and Stem cell therapies are provided in my practice.

3 Disclosures: Graduate of Villanova University Incoming President/Board Interventional Orthopedic Foundation 11/27/2018 3

4 Disclosures Lipogems Consultant

5 Outline Discuss Cells and Sources Processing Pathology Ligaments/Muscles Sacroiliac Joint Facet Radiculopathy Disc

6 Platelet Rich Plasma (PRP) and Lysate PRP (PLRA) Number of Platelets Leukocyte content RBC content Activation Lysate Temperature Mechanical Chemical A Call for a Standard Classification System for Future Biologic Research: The Rationale for New PRP Nomenclature. Mautner et al. PMR 2015

7 Mesenchymal Stem Cells Commonly found in: Bone Marrow Adipose Fat Cells Circulating Blood (few) In Joints (very few) Capillaries (Pericytes)

8 Stem Cell Sources Historically, Bone Marrow stem cells have been felt to be the optimal source of stem cells for Orthopedic conditions There is recent evidence that it may not make a difference with more studies support the use of Adipose-derived stem cells for a variety of orthopedic conditions Adipose tissue requires some level of processing to extract the ADSC that is often beyond FDA restriction of Minimal Manipulation

9 Bone Marrow Aspiration Where Obtained How Obtained Processing RBCs Technical Issues in Harvesting and Concentrating Stem Cells (Bone Marrow and Adipose). Bowen J. PMR 2015

10 Bone marrow was aspirated from 20 patients during total knee arthroplasty Iliac Crest Metaphysis of the Distal Femur Proximal Tibia MSCs were isolated, cultivated and characterized by their immunophenotype and by their in vitro potential for differentiation into osteoblasts, chondroblasts and adipocytes MNC Concentration was significantly higher in the Iliac Crest (10.05 Millions/ml) compared with the femur (0.67 Millions/ml) and tibia (1.7 Millions/ml). Trilineage differentiation was achieved with all samples

11 BMA v. Adipose ADSC High Number of Cells/unit of Tissue Volume Generally 5-50x more in Adipose v. BM More Rapidly Proliferate in Culture Less Susceptible to Senescence in Culture Expansion

12 New System for Harvesting Adipose Closed-loop device for Autologous adipose tissue No centrifuge required Progressively micro-fractures adipose tissue clusters and minimizes inflammatory oily and blood residue Minimally Manipulated (no enzymatic digestion)

13 Is there ANY Evidence It Works?????

14 Spinal Conditions Muscles/Ligaments SIJ Facet Radiculopathy Degenerative Disease Disc Post-Laminectomy

15 Chronic Low Back Pain - Lumbar Muscle Atrophy Effect of autologous platelet leukocyte rich plasma injections on atrophied lumbar multifidus muscle in low back pain patients with monosegmental degenerative disc disease. Hussein, /115 Patient with Chronic Non-Specific LBP Tx: Weekly PLRP x 6. F-U 2 years Outcomes Numeric Pain Scale and Oswestry Disability Index Patient Satisfaction, modified MacNab, Lumbar MRI

16 PLRP - Lumbar Muscles Results No Serious Complications NPS: 8.8 to 3.45 (1 year) ODI: 73.5% to 29.3% (1 year) Outcomes remained stable from months 87.8% Decreased Fatty Multifidus Changes of 1 year MRI Patient Satisfaction 71.2% Mod. MacNab (18 months) 60.2% Excellent and 17.3% Good = 77.5%

17 Sacroiliac Joint About 20% of Low Back Pain

18 Sacroiliac Joint A randomized controlled trial of intra-articular prolotherapy versus steroid injection for sacroiliac joint pain. Kim WM. etal Prolotherapy 23 Prolotherapy Treated Patients 25 Steroid Treated Patients 15 month Follow up Pain Relief and Disability Scores 58.7% Prolotherapy and 10.2% Steroid Improved

19 Case series of Ultrasound-guided Platelet-Rich Plasma Injections for Sacroiliac Joint Dysfunction. Ko G Patients Outcomes: Short McGill Pain Questionnaire, NPS, Oswestry Low Back Pain and Disability Index at 0, 12, 48 months Follow up: Statistical Improvement in Stability, Pain Reduction, and Increase QOL at Maintained at 4 years

20 Steroid vs. Platelet-Rich Plasma in Ultrasound- Guided Sacroiliac Joint Injection for Chronic Low Back Pain Varun Singla, etal. 40 patients with chronic low back pain diagnosed with SIJ pathology were randomly allocated into 2 groups Group S received 1.5 ml of methylprednisolone (40 mg/ml) and 1.5 ml of 2% lidocaine with 0.5 ml of saline, while into ultrasound-guided SIJ injection. Group P received 3 ml of leukocyte-free PRP with 0.5 ml of calcium chloride Intensity of pain was significantly lower in Group P at 6 weeks 1 [1 to 1] vs. 3.5 [2 to 5]; P = ) and 3 months (Median [IQR] = 1 [1 to 3] vs. 5 [3 to 5]; P = ) as compared to Group S MODQ and SF-12 scores were improved initially for up to 4 weeks but deteriorated further at 3 months in Group S, while both the scores improved gradually for up to 3 months in Group P **The efficacy of steroid injection was reduced to only 25% at 3 months in Group S, while it was 90% in Group P

21 Facet Mediated Pain

22 Using Intra-articular Inject Facet Joint and PRPA New Technique for the Treatment of Lumbar Facet Joint Syndrome ion with Autologous Platelet Rich Plasma. Wu. et al. Pain Physician Lumbar Facet Syndrome (8 men, 11 women) Good/Excellent Outcomes Immediate 47% 1 week 74% 1 month 79% 2 months 79% 3 months 79%

23 A Prospective Study Comparing Platelet-Rich Plasma and LA/Corticosteroid in Intra-Articular Injection for the Treatment of Lumbar Facet Joint Syndrome Jiuping Wu, Jingjing Zhou, et al eligible patients with lumbar facet joint syndrome were randomized into group A (intra-articular injection with PRP) and group B (intra-articular injection with LA/corticosteroid) Pain visual analog scale (VAS) at rest and during flexion, and the Roland-Morris Disability Questionnaire (RMQ), Oswestry Disability Index (ODI), and modified MacNab criteria for pain relief and applications of post-treatment drugs All outcome assessments were performed immediately after and at 1 week, 1 month, 2 months, 3 months, and 6 months after treatment

24 A Prospective Study Comparing Platelet-Rich Plasma and LA/Corticosteroid in Intra-Articular Injection for the Treatment of Lumbar Facet Joint Syndrome Jiuping Wu, et al There were No Treatment-related Complications in either group during follow-up Both Groups demonstrated statistical improvements in the pain VAS score at rest or during flexion, the RMQ, and the ODI (P < 0.01) There were significant differences between the 2 groups on the above-mentioned items (P < 0.05).

25 A Prospective Study Comparing Platelet-Rich Plasma and LA/Corticosteroid in Intra-Articular Injection for the Treatment of Lumbar Facet Joint Syndrome Jiuping Wu, et al 1 month Group A (PRP) MacNab criteria (excellent+good): 61.9% Objective success: 61.9% Group B (Steroid) 1 month MacNab criteria (excellent+good): 80% Objective success: 85% 6 months MacNab criteria (excellent+good): 81% Objective success: 81% 6 months MacNab criteria (excellent+good): 50% Objective success: 20%

26 A Prospective Study Comparing Platelet-Rich Plasma and LA/Corticosteroid in Intra-Articular Injection for the Treatment of Lumbar Facet Joint Syndrome Roland-Morris Oswestry Disability Index

27 Regenerative Treatments for Radiculopathy

28 Injecting Platelet Lysate Instead of Steroid Medications Avoid Steroid side effects Possibly Regenerative

29 Cortisone vs PRP Epidural

30 Registry data on PL Epidurals This is data from a prospective, multi-site U.S. registry data, 2015

31 ESI vs. PL Epidurals n Preop n 3 month n 6 month ESI PL/Dex Average Pain ESI PL/Dex 1 0 Preop - Average pain 3 month - Average pain 6 month - Average pain

32 PL for Radicular Pain The use of lumbar epidural injection of platelet lysate for treatment of radicular pain. Centeno. Journal Experimental Orthopaedics (2017) 4: patients (265 male and 205 female) Mean Age: 53.6 Mean BMI: % Adverse events 79.3%: pain, inflammation, soreness, muscle tightness and numbness 20.6%: nausea, emesis, light-headness, skin sensitivity, swelling

33 The use of lumbar epidural injection of platelet lysate for treatment of radicular pain. Centeno. Journal Experimental Orthopaedics (2017) 4:38

34 PL for Radicular Pain - FRI

35 PL Epidural Conclusions Safe No serious AEs!!! Potentially equal or better pain reduction and improved function compared to CSIs More tedious to produce/perform Much more rigorous study on safety and efficacy required!

36 STEM CELLS FOR SPINE (DDD)

37 THOSE WHO FORGET HISTORY..

38 Intradiscal Platelet-Rich Plasma Injection for Chronic Discogenic Low Back Pain: Preliminary Results from a Prospective Trial. Levi et al., Patients 9 Single Level 10 Two Levels 2 Three Levels 1 Five Levels Outcome [VAS >50% & ODI >30% Improvement] 1 month: 14% 2 months: 32% 6 months: 47%

39 Intradiscal Injection of Autologous Platelet-Rich-Plasma Releasate for the Treatment of Discogenic Low Back Pain - Preliminary Prospective Clinical Trial of - 12 Cases ORS 2013 Annual Meeting Akeda, K. etal. Chronic low back pain without leg pain for more than 3 months One or more lumbar discs (L3-4 to L5-S1) with evidence of degenerative changes on magnetic resonance imaging (MRI) At least One symptomatic Disc confirmed using standardized Provocative Discography A soluble releasate, isolated from clotted PRP, was injected (2.0 ml) into the center of the nucleus pulposus under fluoroscopic guidance

40 Intradiscal Injection of Autologous Platelet-Rich-Plasma & Releasate for the Treatment of Discogenic Low Back Pain - Preliminary Prospective Clinical Trial of -12 Cases Akeda, K. etal. ORS 2013 Annual Meeting Before Treatment VAS: 7.7±1.2 RDQ: 13.5±3.8 JOA score 19.6±3.1 After Treatment VAS: 3.1±3.2 RDQ: 2.9±4.2 JOA score: 24.3±3.5 Significantly decreased at one month and it was sustained for 12 months after treatment p<0.01

41 Lumbar Intradiskal Platelet-Rich Plasma (PRP) Injections: A Prospective, Double-Blind, Randomized Controlled Study. Tuakli-Wosornu. Etal. PMR RCT with N=47 29 Treatment 18 control Cross over design at 8 weeks Axial LBP >6 month, Failed conservative Treatment, Positive Discogram, >50% disk height

42 Tuakli-Wosornu et al PMR NO Adverse Events (disc infection, neurologic injury, or progressive herniation) Improved NPS & FRI vs control at 8 weeks 15/18 Controls crossed over at 8 weeks Maintained benefits with significant difference at 12 months 56% of Patients Treated Satisfied

43 PRP and Disc (Reviews) Enhancing intervertebral disc repair and regeneration through biology: platelet-rich plasma as an alternative strategy. Wang S What is the preclinical evidence on platelet rich plasma and intervertebral disc degeneration? Formica M et al 2015 Eur Spine Intradiscal platelet-rich plasma (PRP) injections for discogenic low back pain: an update. Monfett M. et al Repair and Regenerative Therapies of the Annulus Fibrosus of the Intervertebral Disc. Li X [Platelet-rich plasma (PRP) and disc lesions: A review of the literature]. Charneux L. Neurochirurgie What is the clinical evidence on regenerative medicine in intervertebral disc degeneration? Basso M. 2017

44 Intradiscal Stem Cell Studies 11/27/

45 Haufe, et al. Stem Cells Dev Feb;15(1): patients with Symptomatic DDD (axial LBP) Autologous Bone Marrow HSCs Percutaneous injection plus Hyperbaric Oxygen Therapy No improvement in LBP in any patient 8/10 underwent surgery by one year

46 Yoshikawa et al. Spine 2010 May 15;35(11):E patients with LBP and radicular symptoms Autologous culture expanded Bone Marrow MSCs Placed during decompressive surgery with collagen sponge Increased MRI T2 signal, less instability on stress radiographs, clinical improvement in both patients.

47 Meisel et al. Biomol Eng Feb;24(1): patients undergoing Microdiscectomy Autologous cultured expanded chondrocytes (not MSCs) Percutaneous injection 12 weeks post microdisc Cell Tx patients had less LBP at 2 years postop Retained MRI T2 signal (hydration) of treated and adjacent discs

48 Transplantation, 2011 Pilot study with 10 painful, degenerated discs injected with BMC (Autologous & Expanded) All with intact annulus Results examined at 1 year including MRI follow up MRI did not show any restoration of disk height but did have increased water content at 12 months (0.63 to 0.72) Improved LBP, leg symptoms, and MRI T2 signal

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51 Intervertebral Disc Repair with Activated Nucleus Pulposus Cell Transplantation: A Three-Year, Prospective Clinical Study of Its Safety Mochida, et al. European Cells and Materials patients undergoing Lumbar Fusion years old Adjacent disk Pfirrmann s grade 3 Autologous NP cells from fused disc co-cultured with autologous BMSCs Injection 7days post op No Adverse Events at 3 years 8/9 maintained disk grade, 1/9 improved

52 Treatment of Discogenic back pain with autologous BMC injection 26 patients with > 6 months LBP Modified Pfirrmann grade of IV-VII Candidates for surgery BMC was injected into the nucleus pulposus of the symptomatic disc(s) under fluoroscopic guidance Pettine K et al. Treatment of discogenic back pain with autologous bone marrow concentrate injection with minimum two year follow-up. Int Orthop Jan;40(1):135-40

53 13 Single level 13 Two levels Modic changes <3 Disk height loss less than 30% Discogram done in 4 pts in each group Rest decided by MRI/Clinical exam Stem Cells, 2014

54 Results: NO Adverse Effects 9/20 patients with MRI at 1 year showed IMPROVEMENT by blinded reviewer

55 Treatment of Discogenic back pain with autologous BMC injection Results 92 % avoided surgery through 12 months 81 % avoided surgery through 2 years 20 out of 26 patients (77%) showed 1 grade improvement on 1 year MRI 71 % VAS reduction and > 64 % ODI improvements through 2 years

56 Mesoblast (Mesenchymal Precursor cells) Phase I/II FDA Clinical Trial Double Blind RCT at 13 clinical sites N=100 patients with moderate-severe LBP with DDD 60 patients got two doses of Allogeneic culture expanded MSCs in hyaluronic acid for single level DDD Improvement in both groups over HA and saline 3.7-4/10 pain reduction in MSC groups 2.7/10 pain reduction in the HA only and saline groups! ODI: decreased by 35 % in Mesoblast; 30 % HA; 28 % saline. Missed major structural end-point (significant changes in MRI)

57 Conclusions: Bone marrow aspiration has the longest and greatest evidence of efficacy for Orthopedic conditions Consideration for Muscle Injection in Non-Specific Low Back Pain Alternative to Epidural, Facet and SIJ injections instead of corticosteroids Intradiscal for Chronic Discogenic Pain Less Evidence for PRP Better evidence for BMAC (Dose Dependent!)