Autologous implant of bone marrow mononuclear stem-cells as treatment for equine bicipital tendonitis: case report

Menarim, BC; Fortini, GA; Álvarez, PS; Gomez, J. A. Cabrera; Jarrín, CD; Ramírez, A; Galecio, JS

doi:10.4067/s0301-732x2012000300013

Cited by 3 publications

(1 citation statement)

References 15 publications

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“…The mononuclear cell fraction of bone marrow aspirates (bone marrow mononuclear cells -BMNC) is a rich source of proresolving macrophages that have been used therapeutically to improve tissue repair and inflammation resolution (29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39). Macrophages within BMNC are the main drivers of such effect, which's documented pro-resolving functions include increased production of 33), diverse types of prostaglandins and specialized lipid mediators (13,40,41).…”

Section: Introductionmentioning

confidence: 99%

Transcriptional and Histochemical Signatures of Bone Marrow Mononuclear Cell-Mediated Resolution of Synovitis

et al. 2021

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Osteoarthritis (OA) may result from impaired ability of synovial macrophages to resolve joint inflammation. Increasing macrophage counts in inflamed joints through injection with bone marrow mononuclear cells (BMNC) induces lasting resolution of synovial inflammation. To uncover mechanisms by which BMNC may affect resolution, in this study, differential transcriptional signatures of BMNC in response to normal (SF) and inflamed synovial fluid (ISF) were analyzed. We demonstrate the temporal behavior of co-expressed gene networks associated with traits from related in vivo and in vitro studies. We also identified activated and inhibited signaling pathways and upstream regulators, further determining their protein expression in the synovium of inflamed joints treated with BMNC or DPBS controls. BMNC responded to ISF with an early pro-inflammatory response characterized by a short spike in the expression of a NF-ƙB- and mitogen-related gene network. This response was associated with sustained increased expression of two gene networks comprising known drivers of resolution (IL-10, IGF-1, PPARG, isoprenoid biosynthesis). These networks were common to SF and ISF, but more highly expressed in ISF. Most highly activated pathways in ISF included the mevalonate pathway and PPAR-γ signaling, with pro-resolving functional annotations that improve mitochondrial metabolism and deactivate NF-ƙB signaling. Lower expression of mevalonate kinase and phospho-PPARγ in synovium from inflamed joints treated with BMNC, and equivalent IL-1β staining between BMNC- and DPBS-treated joints, associates with accomplished resolution in BMNC-treated joints and emphasize the intricate balance of pro- and anti-inflammatory mechanisms required for resolution. Combined, our data suggest that BMNC-mediated resolution is characterized by constitutively expressed homeostatic mechanisms, whose expression are enhanced following inflammatory stimulus. These mechanisms translate into macrophage proliferation optimizing their capacity to counteract inflammatory damage and improving their general and mitochondrial metabolism to endure oxidative stress while driving tissue repair. Such effect is largely achieved through the synthesis of several lipids that mediate recovery of homeostasis. Our study reveals candidate mechanisms by which BMNC provide lasting improvement in patients with OA and suggests further investigation on the effects of PPAR-γ signaling enhancement for the treatment of arthritic conditions.

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Section: Introductionmentioning

confidence: 99%

Transcriptional and Histochemical Signatures of Bone Marrow Mononuclear Cell-Mediated Resolution of Synovitis

et al. 2021

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Use of autologous products for the treatment of joint and soft tissue disease in horses: A systematic review

2021

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Background: Soft tissue injuries and joint disease are the predominate causes of lameness in the equine athlete and these pathologies carry a guarded prognosis for a return to previous performance. Recently the use of autologous products has become more widespread as a treatment in equine sports medicine. However, the efficacy of these products is yet to be fully established. Objective: To evaluate the current published evidence base regarding the efficacy of autologous products in soft tissue injuries and joint disease. Methods: A systematic review of English articles using MEDLINE, EMBASE and Web of Science databases from 1980 to 2017. The search strategy identified 1594 papers for review. Results: Fifty-eight papers were included in this review, 28 of which were randomised controlled trials. Significant benefit was reported under several parameters, most notably in the use of autologous chondrocytes in artificially induced cartilage defects on histology. One paper documented a significant clinical response under lameness examination. Conclusion: The current literature shows that the treatment of soft tissue injury and cartilage disease with autologous products is safe and that the use of some products can give significant benefit on some outcome measures. True clinical significance is yet to be demonstrated with any product.

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Bone marrow mononuclear cells for joint therapy: The role of macrophages in inflammation resolution and tissue repair

Menarim¹,

MacLeod²,

Dahlgren³

2021

WJSC

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Osteoarthritis (OA) is the most prevalent joint disease causing major disability and medical expenditures. Synovitis is a central feature of OA and is primarily driven by macrophages. Synovial macrophages not only drive inflammation but also its resolution, through a coordinated, simultaneous expression of pro- and anti-inflammatory mechanisms that are essential to counteract damage and recover homeostasis. Current OA therapies are largely based on anti-inflammatory principles and therefore block pro-inflammatory mechanisms such as prostaglandin E 2 and Nuclear factor-kappa B signaling pathways. However, such mechanisms are also innately required for mounting a pro-resolving response, and their blockage often results in chronic low-grade inflammation. Following minor injury, macrophages shield the damaged area and drive tissue repair. If the damage is more extensive, macrophages incite inflammation recruiting more macrophages from the bone marrow to maximize tissue repair and ultimately resolve inflammation. However, sustained damage and inflammation often overwhelms pro-resolving mechanisms of synovial macrophages leading to the chronic inflammation and related tissue degeneration observed in OA. Recently, experimental and clinical studies have shown that joint injection with autologous bone marrow mononuclear cells replenishes inflamed joints with macrophage and hematopoietic progenitors, enhancing mechanisms of inflammation resolution, providing remarkable and long-lasting effects. Besides creating an ideal environment for resolution with high concentrations of interleukin-10 and anabolic growth factors, macrophage progenitors also have a direct role in tissue repair. Macrophages constitute a large part of the early granulation tissue, and further transdifferentiate from myeloid into a mesenchymal phenotype. These cells, characterized as fibrocytes, are essential for repairing osteochondral defects. Ongoing “omics” studies focused on identifying key drivers of macrophage-mediated resolution of joint inflammation and those required for efficient osteochondral repair, have the potential to uncover ways for developing engineered macrophages or off-the-shelf pro-resolving therapies that can benefit patients suffering from many types of arthropaties, not only OA.

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Autologous implant of bone marrow mononuclear stem-cells as treatment for equine bicipital tendonitis: case report

Cited by 3 publications

References 15 publications

Transcriptional and Histochemical Signatures of Bone Marrow Mononuclear Cell-Mediated Resolution of Synovitis

Transcriptional and Histochemical Signatures of Bone Marrow Mononuclear Cell-Mediated Resolution of Synovitis

Use of autologous products for the treatment of joint and soft tissue disease in horses: A systematic review

Bone marrow mononuclear cells for joint therapy: The role of macrophages in inflammation resolution and tissue repair

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