A novel placental tissue biologic, PTP-001, inhibits inflammatory and catabolic responses in vitro and prevents pain and cartilage degeneration in a rat model of osteoarthritis.


Journal

Osteoarthritis and cartilage
ISSN: 1522-9653
Titre abrégé: Osteoarthritis Cartilage
Pays: England
ID NLM: 9305697

Informations de publication

Date de publication:
08 2021
Historique:
received: 22 10 2020
revised: 17 03 2021
accepted: 31 03 2021
pubmed: 24 5 2021
medline: 19 1 2022
entrez: 23 5 2021
Statut: ppublish

Résumé

Characterization of a novel human placental tissue-derived biologic, PTP-001, which is in development as a candidate therapeutic for the treatment of osteoarthritis symptoms and pathophysiology. Human placental tissues from healthy donors were prepared as a particulate formulation, PTP-001. PTP-001 extracts were assayed for the presence of disease-relevant biofactors which could have beneficial effects in treating osteoarthritis. PTP-001 eluates were tested in human chondrocyte cultures to determine effects on the production of a key collagen-degrading matrix metalloproteinase, MMP-13. PTP-001 eluates were also assessed for anti-inflammatory potential in human monocyte/macrophage cultures, as well as for growth-stimulating anabolic effects in human synoviocytes. The in vivo effects of PTP-001 on joint pain and histopathology were evaluated in a rat model of osteoarthritis induced surgically by destabilization of the medial meniscus. PTP-001 was found to contain an array of beneficial growth factors, cytokines and anti-inflammatory molecules. PTP-001 eluates dose-dependently inhibited the production of chondrocyte MMP-13, and the secretion of proinflammatory cytokines from monocyte/macrophage cultures. PTP-001 eluates also promoted proliferation of cultured synovial cells. In a rat osteoarthritis model, PTP-001 significantly reduced pain responses throughout 6 weeks post-dosing. The magnitude and duration of pain reduction following a single intraarticular treatment with PTP-001 was comparable to that observed for animals treated with a corticosteroid (active control). For rats dosed twice with PTP-001, significant reductions in cartilage histopathology scores were observed. PTP-001 represents a promising biologic treatment for osteoarthritis, with a multi-modal mechanism of action that may contribute to symptom management and disease modification.

Identifiants

pubmed: 34023528
pii: S1063-4584(21)00734-2
doi: 10.1016/j.joca.2021.03.022
pii:
doi:

Substances chimiques

Biological Products 0
Cytokines 0
Matrix Metalloproteinase 13 EC 3.4.24.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1203-1212

Informations de copyright

Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Auteurs

C R Flannery (CR)

Bioventus, Durham, NC, USA. Electronic address: carl.flannery@bioventus.com.

S A Seaman (SA)

Bioventus, Durham, NC, USA.

K E Buddin (KE)

Bioventus, Durham, NC, USA.

M A Nasert (MA)

MTF Biologics, Edison, NJ, USA.

E J Semler (EJ)

MTF Biologics, Edison, NJ, USA.

K L Kelley (KL)

University of North Carolina, Chapel Hill, NC, USA.

M Long (M)

MTF Biologics, Edison, NJ, USA.

J Favret (J)

Bolder BioPATH, Boulder, CO, USA.

A Pavesio (A)

Bioventus, Durham, NC, USA.

R F Loeser (RF)

University of North Carolina, Chapel Hill, NC, USA.

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Classifications MeSH