Human mesenchymal stem cells and derived extracellular vesicles reduce sensory neuron hyperexcitability and pain-related behaviors in a mouse model of osteoarthritis

Ai, Minji; Hotham, Willliam E; Pattison, Luke A.; Ma, Qingxi; Henson, Frances; Smith, Ewan St. John

doi:10.1101/2022.02.25.478196

Cited by 2 publications

References 76 publications

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Wheel running, but not home cage activity in Digital Ventilated Cages® is impaired in a mouse model of breast cancer-induced bone pain

Hopkins,

Kanneworff,

Kornum

et al. 2024

Preprint

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Introduction: Cancer-induced bone pain (CIBP) due to metastatic breast cancer is common and debilitating. Effective, long-term treatment options have side effects that reduce patients' quality of life. Preclinical models are a valuable tool to test novel analgesics, but new methods that are translationally and clinically relevant are necessary. This study aimed to assess spontaneous pain-like behaviour of home cage activity and wheel running in Digital Ventilated Cages®. Method: Twenty BALB/cAnNHsd mice were housed in Digital Ventilated Cages®from Tecniplast®with GYM500 home cage running wheels. Mice were assessed by limb use analysis and static weight bearing to determine the development of CIBP and this was compared to the dark-phase home cage activity and wheel running in the Digital Ventilated Cages®. Ten mice underwent 4T1-Luc2 mammary gland adenocarcinoma cell inoculation into the right femur to establish CIBP and another ten mice underwent a sham surgical procedure. Results: The 4T1-inoculated mice displayed pain-like behaviour in limb use and weight bearing tests, demonstrating a preference for the contralateral limb. The limb use scores were compared with home cage activity and wheel running. A reduced wheel running distance corresponded to reduced limb use scores, with the shortest wheel running distances corresponding to the lowest limb use scores. However, this behavioural pattern was not observed in home cage activity, which remained consistent over the study period. Discussion: Reduced wheel running corresponded with reduced limb use scores. This suggests that wheel running behaviour is affected by the development of metastatic breast cancer. However, the home cage activity was not influenced by disease development. Digital Ventilated Cage®wheel running may be a useful behavioural assessment of spontaneous pain-like behaviour of CIBP and may be useful to assess analgesic efficacy.

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Wheel running, but not home cage activity in Digital Ventilated Cages® is impaired in a mouse model of breast cancer-induced bone pain

Hopkins,

Kanneworff,

Kornum

et al. 2024

Preprint

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Intraarticular Injections of Mesenchymal Stem Cells in Knee Osteoarthritis: A Review of Their Current Molecular Mechanisms of Action and Their Efficacy

Rodríguez-Merchán

2022

IJMS

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More than 10% of the world’s population suffers from osteoarthritis (OA) of the knee, with a lifetime risk of 45%. Current treatments for knee OA pain are as follows: weight control; oral pharmacological treatment (non-steroidal anti-inflammatory drugs, paracetamol, opioids); mechanical aids (crutches, walkers, braces, orthotics); therapeutic physical exercise; and intraarticular injections of corticosteroids, hyaluronic acid, and platelet-rich plasma (PRP). The problem is that such treatments usually relieve joint pain for only a short period of time. With respect to intraarticular injections, corticosteroids relieve pain for several weeks, while hyaluronic acid and PRP relieve pain for several months. When the above treatments fail to control knee pain, total knee arthroplasty (TKA) is usually indicated; however, although a very effective surgical technique, it can be associated with medical and postoperative (surgery-related) complications. Therefore, it seems essential to look for safe and effective alternative treatments to TKA. Recently, there has been much research on intraarticular injections of mesenchymal stem cells (MSCs) for the management of OA of the knee joint. This article reviews the latest information on the molecular mechanisms of action of MSCs and their potential therapeutic benefit in clinical practice in patients with painful knee OA. Although most recent publications claim that intraarticular injections of MSCs relieve joint pain in the short term, their efficacy remains controversial given that the existing scientific information on MSCs is indecisive. Before recommending intraarticular MSCs injections routinely in patients with painful knee OA, more studies comparing MSCs with placebo are needed. Furthermore, a standard protocol for intraarticular injections of MSCs in knee OA is needed.

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Human mesenchymal stem cells and derived extracellular vesicles reduce sensory neuron hyperexcitability and pain-related behaviors in a mouse model of osteoarthritis

Cited by 2 publications

References 76 publications

Wheel running, but not home cage activity in Digital Ventilated Cages® is impaired in a mouse model of breast cancer-induced bone pain

Wheel running, but not home cage activity in Digital Ventilated Cages® is impaired in a mouse model of breast cancer-induced bone pain

Intraarticular Injections of Mesenchymal Stem Cells in Knee Osteoarthritis: A Review of Their Current Molecular Mechanisms of Action and Their Efficacy

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