Evolution of PRP and stem cells Lisa A. Fortier, DVM, PhD, DACVS - - PowerPoint PPT Presentation

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Evolution of PRP and stem cells Lisa A. Fortier, DVM, PhD, DACVS - - PowerPoint PPT Presentation

Aug 19, 2023 366 likes •557 views

Cornell University College of Veterinary Medicine Evolution of PRP and stem cells Lisa A. Fortier, DVM, PhD, DACVS James Law Professor of Surgery laf4@cornell.edu Disclosures: Arthrex Consultant, VRN Consultant, Scientific Board Kensey Nash

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Evolution of PRP and stem cells

Lisa A. Fortier, DVM, PhD, DACVS James Law Professor of Surgery laf4@cornell.edu

Disclosures: Arthrex Consultant, VRN Consultant, Scientific Board Kensey Nash

Cornell University College of Veterinary Medicine

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Disclosures

  • Consultant: Arthrex, Veterinary Recommended

Nutraceuticals, TissueGen

  • Royalties: Arthrex
  • Scientific Board: Kensey Nash
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Goal of biologics

  • Repair, restore, regenerate tissue
  • Reduce pain, restore function

Evidence: OA - strong Tendon (upper > lower) - modest Muscle - weak

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What is PRP?

  • No consensus on definition
  • Growth factors released from platelet α-granules

(TGF, PDGF, VEGF, BMPs)

  • Some is good −> more is better
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WBC - degrade normal matrix Platelets - more is not better

Platelets WBC

↑COL1A1:COL3A1 ↑MMP-3 ↑COMP ↑MMP-13 ↓MMP-3 ↓COL1A1:COL3A1 ↓MMP-13 ↓COMP

McCarrel , Fortier JOR, 2010

R² = 0.6459

1 2 3 4 5 6 7 8 9 10 20 30

IL-1B (pg/mL) neutrophils…

Blo…

August 2011 AJSM McCarrell, Fortier, Minas. JBJS 2013 Platelet: WBC ratio Platelets (103/µl) 2000:1 500 2000:1 1500 2000:1 200 NA NA Boswell, Fortier, Minas. AJSM 2013 Yoshida, Murray JOR 2013

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More is not better

  • Synoviocytes

– Assirelli, Knee Surg Sports Traum Arthosc 2014

  • Tendon

– Cross, AJSM 2015

  • ACL

– Yoshida, JOR 2014. JOR 2011

  • Meniscus, cartilage

– Kisiday, Cartilage 2012

  • Pain/function

– Cole, ICRS 2015

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B A B 0.2 0.4 0.6 0.8 1 1.2 1.4 Control ACP HA log HAS-2 Fold Change over Control

HA in synoviocytes

A B A

  • 1.2
  • 1
  • 0.8
  • 0.6
  • 0.4
  • 0.2

Control ACP HA log MMP-13 Fold Change over Control

MMP 13-in synoviocytes

A B B 2 4 6 8 10 12 Control ACP HA TNF-α (pg/ml)

TNF-α in “joint fluid” Sundman, AJSM 2014 Duif C. Arch Orthop Thaum Surg 2015

PRP and OA pain

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A B C D E F G H A I J K L M N O

Group 1: <3 Group 2: =3

Cross, AJSM 2015

A B

Quantitative strain elastography

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PRP and BMC recruit MSCs

PRP PDGF Holmes PLOS ONE 2017

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Cassano KSSTA 2016

Is BMC just PRP with a few MSC?

PRP in femoral condyle BMC in femoral condyle BMC PRP

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IL-1ra / Orthokine / IRAP

BMA BMC-A BMC-B WB PRP MSC + +++ ++

  • TGF-β1, PDGF

+ +++ ++ + +++ Il-1β, IL-8 + ++ ++

  • Reported

IRAP concentrations

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Fallen stem cell paradigms

  • Bunnell. Stem Cell Res and Therapy, 2010.

Fortier, Tuan. Small Animal Surgery, 2011

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MSC licensing / activation

K English, Imm and Cell Bio, 2013 Cassano, Vet Imm 2017 Cassano, SSRT, 2018 Fortier, Sports Health, 2017

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MSC in PTOA

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OC histology –

cartilage and subchondral bone are protected

+ impact control

  • impact

MSC control MSC

  • impact

+ impact

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What we now know

  • MSCs mitigate PTOA
  • They are not immunopriveledged
  • They don’t polarize
  • Activation makes them super stem cells

– Regardless of source

Goodalde Schnabel Hill Cassano

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Rehabilitation basics

Injured

50 µm 50 µm

Pressage

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Acknowledgements