Current status and challenges for cell-cultured milk technology: a systematic review

Abstract

Cellular agriculture is an innovative technology for manufacturing sustainable agricultural products as an alternative to traditional agriculture. While most cellular agriculture is predominantly centered on the production of cultured meat, there is a growing demand for an understanding of the production techniques involved in dairy products within cellular agriculture. This review focuses on the current status of cellular agriculture in the dairy sector and technical challenges for cell-cultured milk production. Cellular agriculture technology in the dairy sector has been classified into fermentation-based and animal cell culture-based cellular agriculture. Currently, various companies synthesize milk components through precision fermentation technology. Nevertheless, several startup companies are pursuing animal cell-based technology, driven by public concerns regarding genetically modified organisms in precision fermentation technology. Hence, this review offers an up-to-date exploration of animal cell-based cellular agriculture to produce milk components, specifically emphasizing the structural, functional, and productive aspects of mammary epithelial cells, providing new information for industry and academia.

Keywords: Cell culture system; Cell-cultured milk; Mammary epithelial cells; Precision fermentation.

Fig. 1

Cellular agriculture technology in the dairy sector and global startup companies to produce milk components. Various global companies are trying to synthesize milk components through fermentation- and animal cell culture-based technology

Fig. 2

Principal processes and technical challenges for producing cell-cultured milk using animal cell culture-based technology. The production of cell-cultured milk, found on the cultivation of mammary epithelial cells (ECs), is through a series of sequential processes as follows: (1) isolation of mammary ECs from parenchymal tissues or milk, (2) cultivation of isolated mammary ECs for the establishment of a cell line, (3) evaluation of cellular characteristics, (4) optimization of cell culture media, (5) establishment of three-dimensional cell culture system using extracellular matrix, (6) upscale of cell cultivation using stirred tank bioreactor and microcarrier, (7) down-stream processing of cell culture media, (8) production of cell-cultured milk components, and (9) processing of cell-cultured milk components. The major technical challenges for the production of cell-cultured milk are resourcing the cell line (1–3), optimizing the cell culture media (4), establishing the cell culture system (5–6), and separating milk components (7–8). Comprehensive and detailed technical challenges for cell-cultured milk production are discussed in this review

Fig. 3

Internal structure of mammary gland and mammary alveolus. The mammary gland is composed of lobes that comprise lobules containing 150–220 alveoli. Mammary alveoli are fundamental constituents that produce milk components. The mammary alveolus consists of parenchymal and stromal compartments based on the basement membrane. The parenchyma is constructed of inner milk secretory epithelial cells that surround a central lumen and outer myoepithelial cells that attach to the base of the mammary epithelium. In addition, the stroma is constituted of adipocytes and extracellular matrix