Give them vasculature and immune cells – how to fill the gap of organoids

Abstract

Valid and relevant models are critical for research to have biological relevance or proceed in the right path. As well-established 2D cell cultures lack niches and cues and rodent models differ in species, 3D organoids emerged as a powerful platform for research. Cultured in vitro from stem cells, organoids are heterogeneous in cells and closely resemble the in vivo settings. Organoids also recapitulate the unique human features if cultured from a human source and are subject to genetic modification. However, one type of organoid possesses only a limited selection of cells. In particular, the absence of vasculature and immune cells restricts the organoids from nutrition, cues, or critical interactions, undermining the validity of organoids as physiological or pathological models. To fill the current gap, there is an urgent need to provide organoids with vasculature and immune cells. In this paper, we review the methods to generate physiological and pathological organoid models and summarize ways to vascularize or immunize them. Our discussion continues with some advantages and disadvantages of each method and some emerging solutions to current problems.

Advanced lung organoids for respiratory system and pulmonary disease modeling

“…Researchers have employed several approaches to co-culture other niche cells with lung organoids. 55 One is mixing fully differentiated niche cells with lung epithelial cells and culturing them together as a single organoid, and the other is co-culturing niche cells with pre-formed lung organoids.…”

“…For instance, the cell engineering for developing multilineage organoids with improved maturation has demonstrated remarkable achievements, which include the production of assembloids by physically fusing different types of organoids or the fabrication of multi-tissue models via multilineage differentiation ( Figure 6(a) ). 3 , 55 Assembloid technique has been primarily applied in brain organoid studies, 204 – 208 and human hepato-biliary-pancreatic organoids were also developed through assembling anterior gut spheroid and posterior gut spheroid. 209 Additionally, simultaneous differentiation of multiple tissue types from single PSC-derived EBs has been achieved through appropriate signaling regulation.…”

Advances in the Generation of Constructed Cardiac Tissue Derived from Induced Pluripotent Stem Cells for Disease Modeling and Therapeutic Discovery

“…Here, we refer to 3D in vitro cardiac tissue platforms as CCTs, including so-called cardiac microtissues (CMTs), cardiac organoids (COs), heart-on-a-chip (HoC), and other engineered heart/cardiac tissues (EHTs/ECTs) [5,8,23,31,34,38,[42][43][44][45][46] (Figure 2). Induced pluripotent stem cells (iPSCs) can differentiate into virtually any cell type and simultaneously grow into multiple cell types (co-emergence) through controlled factor supplementation [7,24,37,39,[46][47][48][49][50], environmental signals, and cell-cell interactions [39,43,46,51]. The differentiation of iPSCs into cardiac cell types is achieved by manipulating cardiogenic signaling, including the Wnt and BMP pathways [5,8,23,32,37,47,[50][51][52][53][54][55][56].…”

“…Monoculture in 2D is quick and easy but dramatically restricts tissue crosstalk and fails to facilitate physiological cell-cell interactions [3][4][5]7,16,24,28,36,[45][46][47][48][49]66]. Cells are interdependent, requiring sufficient contact density to promote cell survival and different cell types to establish homeostatic signaling feedback.…”

Leishmania and Leishmaniasis Research: The Past 50 Years and the Future

“…Information is urgently needed for infectious diseases such as leishmaniasis about how infection is initiated in humans and the subsequent host–parasite interactions that lead to the manifestation of clinical symptoms. A potential tool for such investigations may be 3D human organoid cultures [ 5 , 6 ], with which vascular blood flow can be provided to supply the immune cells necessary for the study of infection and immunity [ 7 , 8 ]. The individualized organoids of such designs have the potential to facilitate precision or personalized medicine, which is predicted to be essential for future healthcare [ 9 ] by, for example, supplementing or replacing population-based clinical trials of drugs and vaccines for infectious diseases.…”