Abstract
The phenotypic change of macrophages (Mφs) plays a crucial role in the musculoskeletal homeostasis and repair process. Although mesenchymal stem cells (MSCs) have been shown as a novel approach in tissue regeneration, the therapeutic potential of MSCs mediated by the interaction between MSC-derived paracrine mediators and Mφs remains elusive. This review focused on the elucidation of paracrine crosstalk between MSCs and Mφs during musculoskeletal diseases and injury. The search method was based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and Cochrane Guidelines. The search strategies included MeSH terms and other related terms of MSC-derived mediators and Mφs. Ten studies formed the basis of this review. The current finding suggested that MSC administration promoted proliferation and activation of CD163+ or CD206+ M2 Mφs in parallel with reduction of proinflammatory cytokines and increase in anti-inflammatory cytokines. During such period, Mφs also induced MSCs into a motile and active phenotype via the influence of proinflammatory cytokines. Such crosstalk between Mφs and MSCs further strengthens the effect of paracrine mediators from MSCs to regulate Mφs phenotypic alteration. In conclusion, MSCs in musculoskeletal system, mediated by the interaction between MSC paracrine and Mφs, have therapeutic potential in musculoskeletal diseases.
Highlights
The inflammatory processes in response to musculoskeletal diseases and injury, such as bone fractures, osteoarthritis (OA), osteoporosis, tendon injuries, and muscle injuries, are essential for the correct restoration of structure and function to the affected area (Bosurgi et al, 2011; Mianehsaz et al, 2019; Pajarinen et al, 2019; Wang et al, 2019; Yang and Yang, 2019)
Proinflammatory Mφs are identified as the classic M1 Mφs, which are involved in the early stages of tissue repair, whereas the anti-inflammatory Mφs are identified as M2 Mφs, which dominated later stages of tissue repair (Murray et al, 2014; Spiller and Koh, 2017)
Five mesenchymal stem cells (MSCs) and Mφs cell sources for EVs isolation were described in these selected studies: human (Lo Sicco et al, 2017; Hyvarinen et al, 2018; Zhang et al, 2018; Chamberlain et al, 2019; Pacienza et al, 2019), cell lines (Pacienza et al, 2019), Sprague–Dawley rats (Shi et al, 2019), C57BL/6 mice (Chang et al, 2015; Cosenza et al, 2017; Lo Sicco et al, 2017; Li Y. et al, 2019), and transgenic mice [scleraxis–green fluorescent protein (GFP) tendon reporter mice, nuclear factor (NF-κB)–GFP–luciferase transgenic reporter mice, and wild-type FVB/NJ (FVB) mice] (Shen et al, 2020)
Summary
The inflammatory processes in response to musculoskeletal diseases and injury, such as bone fractures, osteoarthritis (OA), osteoporosis, tendon injuries, and muscle injuries, are essential for the correct restoration of structure and function to the affected area (Bosurgi et al, 2011; Mianehsaz et al, 2019; Pajarinen et al, 2019; Wang et al, 2019; Yang and Yang, 2019). Crosstalk Between MSCs and Macrophages the dysregulation of inflammatory reactions can aggravate the tissue healing results (Saldana et al, 2019). Macrophages (Mφs) are the critical regulators involved in initiation, propagation, and resolution of inflammatory response throughout the tissue regenerative process. Mφs have a broad spectrum of adaptive phenotypes and functional transitions that might exacerbate and resolve inflammation during tissue repair process (Saldana et al, 2019). The early presence of M1 Mφs initiates tissue repair, but the persistent of M1 activity can deteriorate the repair process (Krzyszczyk et al, 2018). The undisciplined regulation of Mφ phenotypic change impairs tissue repair, and each of the subtypes might have specific functions; further investigation is needed to identify the explicit role of M2 subtypes (O’Brien et al, 2019)
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