Invited review: mesenchymal progenitor cells in intramuscular connective tissue development

Abstract

The abundance and cross-linking of intramuscular connective tissue contributes to the background toughness of meat, and is thus undesirable. Connective tissue is mainly synthesized by intramuscular fibroblasts. Myocytes, adipocytes and fibroblasts are derived from a common pool of progenitor cells during the early embryonic development. It appears that multipotent mesenchymal stem cells first diverge into either myogenic or non-myogenic lineages; non-myogenic mesenchymal progenitors then develop into the stromal-vascular fraction of skeletal muscle wherein adipocytes, fibroblasts and derived mesenchymal progenitors reside. Because non-myogenic mesenchymal progenitors mainly undergo adipogenic or fibrogenic differentiation during muscle development, strengthening progenitor proliferation enhances the potential for both intramuscular adipogenesis and fibrogenesis, leading to the elevation of both marbling and connective tissue content in the resulting meat product. Furthermore, given the bipotent developmental potential of progenitor cells, enhancing their conversion to adipogenesis reduces fibrogenesis, which likely results in the overall improvement of marbling (more intramuscular adipocytes) and tenderness (less connective tissue) of meat. Fibrogenesis is mainly regulated by the transforming growth factor (TGF) β signaling pathway and its regulatory cascade. In addition, extracellular matrix, a part of the intramuscular connective tissue, provides a niche environment for regulating myogenic differentiation of satellite cells and muscle growth. Despite rapid progress, many questions remain in the role of extracellular matrix on muscle development, and factors determining the early differentiation of myogenic, adipogenic and fibrogenic cells, which warrant further studies.

Review: Enhancing intramuscular fat development via targeting fibro-adipogenic progenitor cells in meat animals

“…Besides, the abundance of PDGFRA in finishing Angus is correlated with its higher IMF contents when compared with Nellore (Martins et al, 2015). Thus PDGFRA is a marker of intramuscular adipocyte progenitors in beef cattle (Huang et al, 2012a;Miao et al, 2016). In pigs, PDGFRA þ cells are located in the gaps of myofibers in longissimus dorsi muscle, and more PDGFRA þ cells are detected in longissimus dorsi muscle of fat-type pigs compared with that of lean-type pigs at 180 days of age (Sun et al, 2017), albeit no difference was observed in the abundance of PDGFRA þ cells or PDGFRA expression between longissimus thoracis (with higher IMF contents) and semitendinosus muscle (with lower IMF) in 180-day-old pigs (Chen et al, 2019).…”

“…Regulation of the adipogenic differentiation of fibro-adipogenic progenitors Fibro-adipogenic progenitors possess both fibrogenic and adipogenic potentials, and fibrogenesis of intramuscular FAPs has been depicted in our previous review (Miao et al, 2016). Because both adipocytes and fibroblasts are derived from FAPs, it had been postulated that enhancing adipogenic differentiation may correspondingly reduce fibrogenesis.…”

“…Specifically, TGFβ1, secreted from macrophages during the regeneration phase in damaged muscle, is the most critical profibrogenic cytokine via stimulating the receptor-SMAD cascades (Miao et al, 2016). Transforming growth factor β1 represses adipogenic differentiation of FAPs both in vivo and ex vivo (Lee, 2018;Zhang et al, 2019a).…”

Tissue Engineering for Clean Meat Production

“…Addition of LIF (Austin and Burgess, 1991;Nicola and Babon, 2015), heparin-binding epidermal growth factor (hb-EGF) (Thornton et al, 2015), TGFβ (Vitello et al, 2004) and insulin-like growth factor 1 (IGF-1) (Allen and Boxhorn, 1989;Vitello et al, 2004) can improve BSC proliferation. In addition to its central role in muscle development, TGF-β contributes to mature skeletal muscle mass, and is a key regulator of intramuscular fibrogenesis (Kollias and McDermott, 2008;Miao et al, 2016). In addition, it was shown that TGF-β1 suppressed myogenesis in 2D cultures, while enhancing myogenesis in 3D cultures, rendering it a valuable regulator of in-vitro muscle tissue development (Krieger et al, 2018).…”

“…The skeletal muscle ECM is responsible for tissue elasticity, generates adhesion points for cell adherence, provides cells with a 3D environment and regulates cell proliferation, differentiation, migration, morphology and alignment via biochemical and biophysical cues (Tse and Engler, 2011;Hausman, 2012;Chaturvedi et al, 2015;Fuoco et al, 2016;Grzelkowska-Kowalczyk, 2016). The ECM composition and roles are not constant, but change during the muscle development in a process called fibrogenesis, in parallel to myogenesis and adipogenesis (Thorsteinsdóttir et al, 2011;Yan et al, 2013;Miao et al, 2016). In addition to its biological roles, the ECM contains nutrients such as proteins (mostly collagens), and glycosaminoglycans [mostly hyaluronic acid (HA)], and affects the tissue texture and the overall quality of the meat (Purslow, 2005;Guo et al, 2015;Duffy et al, 2016;Listrat et al, 2016;Huang et al, 2017).…”