Fututure Food! Tsinghua University successfully cultivated meat balls with cells, and its soft and hard texture is comparable to that of food pork balls!
Cell cultured meat is a new field of interdisciplinary fields such as cell biology and tissue engineering in the past decade. Cultured meat derived from animal muscle cells aims to solve the disadvantages of traditional animal husbandry, which consumes huge space and energy and is not environmentally friendly. The technical difficulty of cell cultured meat lies in how to expand muscle and adipose progenitor cells on a large scale in vitro and induce them to differentiate efficiently towards mature cells; and how to use tissue engineering technology to create artificial muscles with a highly bionic microstructure organize.
On May 30, 2022, Professor Du Yanan's research group from Tsinghua University School of Medicine published a paper entitled "Engineered meatballs via scalable skeletal muscle cell expansion and modular micro-tissue assembly using porous gelatin micro-carriers ("Biomaterials") magazine. Large-scale expansion of muscle cells with porous gelatin microcarriers and artificial meatball technology for modular bioassembly)” research paper. The study found that muscle and adipose progenitor cells can rapidly expand and differentiate and mature on edible porous gelatin microbioscaffolds (microcarriers); further use of bioassembly technology can aggregate muscle and adipose microtissue raw materials into several centimeters in size artificial meatballs.
Figure 1. From large-scale expansion of cells to tissue engineering construction of artificial meatballs
The researchers found that the porous gelatin microcarrier is an excellent microscaffold for 3D cell culture. In a stirred bioreactor, porcine primary muscle astrocytes (i.e., porcine skeletal muscle stem cells) and C2C12 mouse myoblasts grown on porous gelatin microcarriers can efficiently expand up to 20-fold within 7 days. At the same time, the three-dimensional porous structure of the microcarrier saves the consumption of medium compared with the traditional 2D cell culture flask, thereby reducing the cost of artificial meatballs. Interestingly, skeletal muscle stem cells spontaneously differentiate towards mature muscle cells and synthesize myosin heavy chain (expression of this protein) without the addition of traditional muscle differentiation-inducing components such as horse serum. marks the differentiation and maturation of muscle cells). In addition, using 3D-printed meat ball molds and a food additive glutamine transaminase (as a cross-linking agent for muscle tissue), pig muscle microtissues of about a few hundred microns can be assembled into artificial pork balls with a size of several centimeters. The soft and hard texture of the artificial pork balls is comparable to that of traditional food pork balls, while it is higher in protein and lower in fat.
Figure 2. Morphology of cell-cultured pork products before (a, c) and after (b, d) cooking, and comparison of firmness (e) and nutritional content (f) with edible pork balls (lion head) made from natural pork
Porous gelatin microcarriers also supported the expansion and further differentiation of adipose precursor cells in 3T3L1 mice, which developed into fat droplet-rich adipocytes within 10 days. Modular biological assembly of 3T3L1 fat microtissues and C2C12 muscle microtissues in a certain proportion can further create "fat and thin" artificial meatballs.
Figure 3. "Fat and lean" artificial meatballs formed by bio-assembled mouse muscle and adipose microtissues
In conclusion, this study shows that the use of edible porous gelatin microcarriers combined with stirred bioreactors can efficiently and scale-up expansion of muscle and adipose progenitor cells in vitro and induce their differentiation and maturation. Subsequently, the harvested mature muscle and adipose micro-tissues were assembled into "fat and lean" artificial meatballs in a certain proportion in a 3D-printed meatball mold. This technology can serve a variety of tissue engineering application scenarios such as meat-based cell culture meat and muscle regeneration.
Professor Du Yanan of Tsinghua University School of Medicine is the corresponding author of the paper, and Liu Ye, a postdoctoral fellow of Tsinghua University School of Medicine, is the first author of the paper. The porous gelatin microcarriers and agitated bioreactors used in this paper are based on related commercial products of Beijing Huakan Biotechnology Co., Ltd.; pig primary muscle astrocytes were donated by Associate Professor Ding Shijie of Nanjing Agricultural University. This research was supported by the National Science Foundation for Distinguished Young Scholars (82125018) and the China Postdoctoral Science Foundation Station Front Special Grant (043220062).
Original link
https://doi.org/10.1016/j.biomaterials.2022.121615
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