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

Abstract

Objective: 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. Methods: 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. Results: 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. Conclusions: 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.

Single-cell transcriptome landscape of zebrafish liver reveals hepatocytes and immune cell interactions in understanding nonalcoholic fatty liver disease

“…1 ( 31 ), and Hep3 expressing msmo1 ( 23 ) and hmgcs1 ( 23 ). The immune cell types identified included lymphocytes (expressing zap70 ( 32 ), il7r ( 33 ) and ifng1 ( 34 )), neutrophils/monocytes (expressing mmp13a ( 35 ), mmp9 ( 36 ), lyz ( 37 ) and lect2l ( 38 )), and eosinosphils (expressing viml ( 39 ), hp ( 39 ), cd81a ( 39 ) and gata2a ( 39 )). Marco ( 40 ), cxcl8a ( 41 ) and csf1ra ( 42 ) were highly expressed in noninflammatory macrophages, while grn1 ( 43 ), mpeg1 .…”

“…Nonimmune cell types primarily consisted of three hepatocyte subclusters: Hepatocyte (Hep) 1 expressing aqp12 (27) and itih2 (28), Hep 2 expressing ahsg1 (29), apoa1a (30) and apoa4b.1 (31), and Hep3 expressing msmo1 (23) and hmgcs1 (23). The immune cell types identified included lymphocytes (expressing zap70 (32), il7r (33) and ifng1 (34)), neutrophils/monocytes (expressing mmp13a (35), mmp9 (36), lyz (37) and lect2l (38)), and eosinosphils (expressing viml (39), hp (39), cd81a (39) and gata2a (39)). Marco (40), cxcl8a (41) and csf1ra (42) were highly expressed in noninflammatory macrophages, while grn1 (43), mpeg1.1 (44) and cxcr4b (45) were predominantly expressed in inflammatory macrophages.…”

Human Adipose- and Amnion-Derived Mesenchymal Stromal Cells Similarly Mitigate Osteoarthritis Progression in the Dunkin Hartley Guinea Pig

“…First, to the best of the authors' knowledge, this is the first study to perform a head-to-head comparison of MSCs in an in vivo model of spontaneous OA. Second, although previous reports have evaluated amnion-derived products in mitigating OA, 5,14,42 commercially available products often do not contain viable cells as a result of the processing and sterilization procedures utilized during manufacturing. Finally, although others have employed the DHGP model to evaluate the efficacy of a single injection of 1 MSC source to mitigate OA progression, 28 previous work primarily evaluated histological outcomes.…”

An update on the effect of intra-articular intervention strategies using nanomaterials in osteoarthritis: Possible clinical application

“…Unlike other conventional autologous therapies (e.g., ASCs, BMAC and PRP), PTP-001 is a room-temperature (“off-the-shelf”) stable therapeutic agent being resuspended in saline instantly before use. In a study, Flannery et al (2021) characterized the biochemical features of PTP-001 in OA progression using interesting periclinal in vitro and in vivo models. PTP-001 contains multiple beneficial substances, such as growth factors, anti-inflammatory molecules, and cytokines.…”