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.
Animals
Arthralgia
/ drug therapy
Biological Products
/ pharmacology
Cell Proliferation
/ drug effects
Cells, Cultured
Chondrocytes
/ metabolism
Cytokines
/ metabolism
Disease Models, Animal
Female
Humans
Matrix Metalloproteinase 13
/ metabolism
Osteoarthritis
/ drug therapy
Placenta
/ chemistry
Pregnancy
Rats
Synovial Membrane
/ cytology
Allograft
Amnion
Amniotic
Chorion
Growth factor
Umbilical cord
Journal
Osteoarthritis and cartilage
ISSN: 1522-9653
Titre abrégé: Osteoarthritis Cartilage
Pays: England
ID NLM: 9305697
Informations de publication
Date de publication:
08 2021
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
1203-1212Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.