Experimental Control of Macrophage Pro-Inflammatory Dynamics Using Predictive Models

Weinstock, Laura D.; Forsmo, James E.; Wilkinson, Alexis; Ueda, Jun; Wood, Levi B.

doi:10.3389/fbioe.2020.00666

Cited by 4 publications

(2 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While macrophages are present throughout the healing process, macrophage depletion studies have identified that their presence is most critical in the immediate aftermath of injury during the pro-inflammatory phase ( 28 – 31 ). Polarized macrophages have been shown to exhibit plasticity in their ability to revert back to a naïve resting state in vitro ( 32 ) and through predictive modeling ( 33 ). Inflammatory macrophages demonstrate reduced inducible nitric oxide synthase (iNOS) signaling as time progresses after pro-inflammatory stimulation, eventually returning to a naïve state.…”

Section: Hematoma Formation and Inflammatory Phasementioning

confidence: 99%

Temporal dynamics of immune-stromal cell interactions in fracture healing

Capobianco,

Hankenson,

Knights

2024

Front. Immunol.

View full text Add to dashboard Cite

Bone fracture repair is a complex, multi-step process that involves communication between immune and stromal cells to coordinate the repair and regeneration of damaged tissue. In the US, 10% of all bone fractures do not heal properly without intervention, resulting in non-union. Complications from non-union fractures are physically and financially debilitating. We now appreciate the important role that immune cells play in tissue repair, and the necessity of the inflammatory response in initiating healing after skeletal trauma. The temporal dynamics of immune and stromal cell populations have been well characterized across the stages of fracture healing. Recent studies have begun to untangle the intricate mechanisms driving the immune response during normal or atypical, delayed healing. Various in vivo models of fracture healing, including genetic knockouts, as well as in vitro models of the fracture callus, have been implemented to enable experimental manipulation of the heterogeneous cellular environment. The goals of this review are to (1): summarize our current understanding of immune cell involvement in fracture healing (2); describe state-of-the art approaches to study inflammatory cells in fracture healing, including computational and in vitro models; and (3) identify gaps in our knowledge concerning immune-stromal crosstalk during bone healing.

show abstract

Section: Hematoma Formation and Inflammatory Phasementioning

confidence: 99%

Temporal dynamics of immune-stromal cell interactions in fracture healing

Capobianco,

Hankenson,

Knights

2024

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…To resolve chronic inflammation, an acute event is needed to bring in immune cells and activate different inflammatory cascades to resolve and induce a pro-regenerative response. 74 This mechanism is common in other chronic inflammatory environments and wound healing environments where acute inflammatory events are necessary to resolve chronic inflammation and transition to pro-regenerative immune responses to regulate inflammation. [75][76][77] Furthermore, the pro-inflammatory cytokines that showed increased expression in the current study (IL-6, IL-7, IL-8) have been implicated as significant mediators in wound healing and similar diseases that involve resolution of inflammatory events.…”

Section: Biomaterials Encapsulation Of Hmscs Induced a Targeted Paracrmentioning

confidence: 99%

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

Ka²,

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

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□, a key cytokine involved in OA. Non-encapsulated hMSCs showed an indiscriminate increase in all cytokines in response to IL-1□ while encapsulated hMSCs showed a highly targeted secretory response with increased expression of some pro-inflammatory (IL-1β, 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.

show abstract