Outline. Regenera-ve Medicine. Regenera-ve Medicine: Stem Cell Therapy and Platelet Rich Plasma (PRP) 10/3/15

Transcription

1 Regenera-ve Medicine: Stem Cell Therapy and Platelet Rich Plasma (PRP) Kris-n Kirkby Shaw, DVM, PhD, CCRT Diplomate ACVS & ACVSMR Outline Stem Cell Therapy Science and evidence Treatment Platelet Rich Plasma Science and evidence Treatment Case Examples Regenera-ve Medicine The use of mul+- potent, pluri- potent or isolated cells that replace or induce the regenera+on of damaged +ssue 1

2 Regenera-ve Medicine No single target receptor (vs pharmaceu-cals) Autogenous vs. allogeneic Stem Cells Pluripotent: differen-ate into any type of cell self renewal embryonic stem cells teratoma Mul-potent: differen-ate into limited line of cells maintain and repair the organ they are from self renewal adult stem cells 2

3 Proper-es of Regenera-ve Cells Differen-ate: tendon, bone, car-lage, cardiac, nervous, muscle, vascular, liver Induce repair: secrete VEGF, FGF, TFG- beta Homing: respond and migrate to site of injury/ inflamma-on Immunomodula-on: decrease IL- 1, suppress T- cell prolifera-on An-- apoptosis Self- renewal Indirect Effects of MSC Yi T and Song SU Arch Pharm Res 2012 Stromal Vascular Frac-on Adipose derived MSC immunomodulatory/ an-- inflammatory Endothelial progenitor cells angiogenesis M2 macrophages immunomodulatory IL- 1, IL- 10 antagonist T- regulatory cells immunosuppressive Riordan NH J Translat Med

4 Autogenous Stem Cell Therapy Adipose collec-on: falciform, other Source of high numbers of MSC expansion not typically required Vascular stromal frac-on isolated Requires minor surgical procedure Research supports its use Bone marrow can be a source Requires culturing of cells Autogenous, Adipose- Derived Stem Cell Therapy Day 0: Harvest fat, Fed- Ex over night to Vet Stem Vet and Owner outcome measures Autogenous, Adipose- Derived Stem Cell Therapy Day 1 at Vet Stem Vascular stromal frac-on isolated, returned overnight to vet Banked dose(s) Reten-on dose 4

5 Autogenous, Adipose- Derived Stem Cell Therapy Day 2: Administered intra- ar-cular Seda-on required Cost to owner: ~$ /- addi-onal surgery, i.e. elbow arthroscopy Some insurance plans cover Current Indica-ons for SCT in Veterinary Pa-ents Osteoarthri-s Ligament, tendon and muscle injuries Osteochondrosis Immune- mediated polyarthri-s Fractures Outcome Expecta-ons 75% of dogs will have a posi-ve outcome that the owner will observe by 60 days 80% of owners report improvement in QOL by 90 days Set expecta-ons so owners don t expect to get a puppy back- - unless they own a puppy! 2/3 of dogs go past one year without re- treatment Vet Stem Data 5

6 Retrospec-ve Canine OA Cases: Vet Stem Data Data courtesy of Vet Stem Reviewing the Evidence 6

7 Vet Therapeu+cs 2007 Hip OA 21 dogs Placebo control Improved lameness, range of mo-on and pain on manipula-on Effect seen at 30 days Vet Therapeu+cs client owned dogs Significantly decreased lameness and disability No significant difference in pain on manipula-on Improvement seen from days Not blinded or placebo controlled Stem Cell Discovery 2012 Acute semitendinosis tears Treated 1-3 weeks ajer injury Intralesional, perilesional and IV Ultrasound at 6,10 weeks Resolu-on and return to work 7

8 Quality Control Processing lab must have QC system in place Sterility Validated procedures Cer-fied trained technicians Calibrated equipment Quality assurance inspec-ons Dose control- - cell count/ viability Morrison D et al. Stem cell coun-ng methods can lead to inaccurate dosing. Bioprocessing J, Limita-ons of Autogenous SCT Anesthesia and surgery needed to collect cells Cost, morbidity Older and sick pa-ents may not have as viable cells Heterogeneous mixture of stem cells and other cells S-ll don t know op-mal # cells, treatment frequency Effect on concurrent neoplasia Need addi-onal clinical studies Poten-al Addi-onal Uses Perianal fistulas Atopy Liver failure Renal failure Cys--s IBD/ Chron s disease Addi-onal auto- immune condi-ons Dilated cardiomyopathy Ischemic heart disease Leukemia Diabetes Parkinson's Alzheimer's Mul-ple sclerosis Spinal cord injury 8

9 Summary of Stem Cell Therapy Effects Tissue repair and regenera-on Immunomodula-on An-- inflammatory Treat early in disease process Blood Components RBCs: ~45% WBCs: ~1% Platelets: <1% Plasma: 55% 92% water 8% proteins Serum: no fibrin or closng factors Platelets First step in any healing is platelet ac-va-on Chronic wounds need to be re- set Clot forma-on = hemostasis Growth factor release from alpha granules 90% released in first 10 minutes ac-vate WBC and fibroblasts PDGF, TGF- b, EGF, IGF, VEGF, bfgf, ECGF 9

10 The "Goods" Platelet Rich Plasma Autogenous blood centrifuged to isolate plasma and platelets +/- WBC Op-mal platelet concentra-on not known 2x vs 5x Therapeu-c window Weibrich et al Bone 2004;34: Several methods available SVP, ProTec, Arthrex (ACP), Magellan Differ in amount of blood needed, platelet concentra-on, expense, ease Indica-ons for PRP Bone healing Tendons, ligaments core lesion Wounds topical gel Joints peri- ar-cular intra- ar-cular 10

11 PRP Treatment Seda-on +/- US guidance Sterile technique Can not store once ac-vated Expect pain ajer No NSAIDs? Rest for 2 weeks ajer Stem Cell Therapy Case Examples CKL ES PI Therapy and Crisis Response Dog Pickles.Lackey@gmail.com Pickles_11x17.indd 1 7/10/12 8:18 AM Pickles 11 month F Lab Shijing leg lameness Improved with Adequan, NSAIDs Lej FCP Stem cells collected, treated at -me of arthroscopy and OVH 11

12 Pickles Crisis Response Therapy Dog Kiyy 9 y FS Cayle Dog Bilateral elbow OA Previous hemilaminectomy Arthroscopy, stem cell therapy, laser, rehab Re- treated 6 months ajer ini-al treatment I feel like I have my dog back Taffy 12

13 Stem Cells and Elbows Treat as early as possible Ideally at -me of scope Rest 2-6 weeks ajer injec-on Follow up q 30 days Rehabilita-on plan Part of mul-- modal therapy Repeat q 6-12 months PRP Case Example Nitro: 4 y MN English Pointer High level hun-ng dog Ini-al presenta-on: bilateral/ shijing leg intermiyent NWB lameness Referred for suspect CCLR PE: No lameness on W/T/R, normal transi-ons, normal s-fle exam, bilateral distal Achilles thickening, normal tarsal and digit ROM 13

14 Ultrasound Right Achilles Diagnosis: Bilateral Achilles Tedinopathies Right: Grade IIb Lej: Grade III Achilles Tendon Injuries Grade I: Complete rupture all components Grade IIa: Musculotendinous rupture Grade IIb: Tendon rupture, paratendon intact, core lesion Grade IIc: Tendon avulsion from bone, SDF intact, hyperflexion of digits Grade III: Tendinosis, thickening of tendon but normal stance Meustage FJ VCOT

15 Plan ESWT- - bilateral PRP- - R core lesion Custom Ortho-cs (Ortho Pets) Dynamize In- house rehabilita-on Home exercise plan Custom Ortho-cs Physical Rehabilita-on Progressive rehab plan Ajer 6 months, some ac-vity without orthosis 15

16 Home Exercise and Ac-vity Log 1 year: Sport Braces THANK YOU! Questions? Copyright 2015 Animal Surgical Clinic of Sea:le. All rights reserved. 16

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