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Biology subjects

Doan, T. N.

Publications and source records attributed to Doan, T. N..

2 recordsLinked to original sources

Effect of human synovial fluid from osteoarthritis patients and healthy individuals on lymphatic contractility

The lymphatic system has been proposed to play a crucial role in the development and progression of osteoarthritis (OA). The synovial fluid (SF) of arthritic joints contains mediators of the inflammatory response and products of the injury to articular tissues, while lymphatic system plays a critical role in resolving inflammation and overall joint homeostasis. Despite the importance of both the lymphatic system and SF in OA disease, their relationship is still poorly understood. Here, we utilized SF derived from osteoarthritis patients (OASF) and healthy individuals (HSF) to investigate potential effects of SF on migration of lymphatic endothelial cells (LECs) in vitro, and lymphatic contractility of femoral lymphatic vessels (LVs) ex vivo. Both OASF and HSF treatments led to an increased migratory response in vitro compared to LECs treatment with media without serum. Ex vivo, both OASF and HSF treatments to the lumen of isolated LVs led to significant differences in the tonic and phasic contractions and these observations were dependent on the SF treatment time. Specifically, OASF treatment transiently enhanced the RFLVs tonic contractions. Regarding the phasic contractions, OASF generated either an abrupt reduction after 1 hr of treatment or a complete cease of contractions after an overnight treatment, while HSF treatment displayed a gradual decrease in lymphatic contractility. The observed variations after SF treatments suggest that the pump function of lymphatic vessel draining the joint could be directly compromised in OA and thus might present a new therapeutic target.

bioengineering

Biomaterial encapsulation of human mesenchymal stromal cells modulates paracrine signaling response and enhances efficacy for treatment of established osteoarthritis

Mesenchymal stromal cells (MSCs) have shown promise as a treatment for osteoarthritis (OA); however, effective translation has been limited by numerous factors ranging from high variability and heterogeneity of hMSCs, to suboptimal delivery strategies, to poor understanding of critical quality and potency attributes. The objective of the current study was to assess the effects of biomaterial encapsulation in alginate microcapsules on human MSC (hMSC) secretion of immunomodulatory cytokines in an OA microenvironment and therapeutic efficacy in treating established OA. Lewis rats underwent Medial Meniscal Transection (MMT) surgery to induce OA. Three weeks post-surgery, after OA was established, rats received intra-articular injections of either encapsulated hMSCs or controls (saline, empty capsules, or non-encapsulated hMSCs). Six weeks post-surgery, microstructural changes in the knee joint were quantified using contrast enhanced microCT. Encapsulated hMSCs attenuated progression of OA including articular cartilage degeneration (swelling and cartilage loss) and subchondral bone remodeling (thickening and hardening). A multiplexed immunoassay panel (41 cytokines) was used to profile the in vitro secretome of encapsulated and non-encapsulated hMSCs in response to IL-1{square}, a key cytokine involved in OA. Non-encapsulated hMSCs showed an indiscriminate increase in all cytokines in response to IL-1{square} while encapsulated hMSCs showed a highly targeted secretory response with increased expression of some pro-inflammatory (IL-1{beta}, IL-6, IL-7, IL-8), anti-inflammatory (IL-1RA), and chemotactic (G-CSF, MDC, IP10) cytokines. These data show that biomaterial encapsulation using alginate microcapsules can modulate hMSC paracrine signaling in response to OA cytokines and enhance the therapeutic efficacy of the hMSCs in treating established OA.

bioengineering