Silent saboteurs: How microplastics disrupt stem cells and tissue regeneration

Table 1 Evidence of microplastics already present in the human body

Location	Size of microplastics	Concentration/abundance of microplastics	Testing method	Ref.
Brain	100-200 nm	4917 μg/g	Py-GC/MS	[42]
Bone	138.86 ± 105.67 μm	22.9 ± 15.7 particles/g	Raman spectra	[43]
Bone marrow	20-500 μm	51.29 μg/g	Py-GC/MS	[44]
Blood	≥ 700 nm	1.6 μg/mL	Py-GC/MS	[6]
Kidney	1-5 μm	404 μg/g	Py-GC/MS	[42]
Lung	3 μm	1.42 ± 1.50 MP/g	μFTIR spectroscopy	[45]
Placenta	> 1 μm	126.8 ± 147.5 μg/g	Py-GC/MS	[7,46]
Breast milk	20-50 μm	20.2 particles/g	Laser infrared imaging spectrometer	[47]
Liver	1-5 μm	433 μg/g	Py-GC/MS	[42]
Testis	21.76-286.71 μm	11.60 ± 15.52 particles/g	Py-GC/MS	[48,49]
Colon	1.1 ± 0.3 mm	28.1 ± 15.4 particles/g	μFTIR spectroscopy	[50]

Py-GC/MS: Pyrolysis gas chromatography-mass spectrometry; MP: Microplastic; μFTIR: Micro Fourier transform infrared.

Table 2 Application of organoids in microplastic research

Organoid	Source	Type of MPs	Size of MPs	Concentration of MPs	Biological effects	Ref.
Cardiac organoids	hESC	PS	28-29 nm	5 and 20 μg/mL	MPs impeded differentiation of hESCs; autophagy and p38/ERK MAPK signaling pathways	[86]
	hPSCs	PS	956 nm	0.025-2.5 μg/mL	Cardiotoxic; destruction of mitochondrial function	[87]
Cerebral organoids	hiPSCs	PS	25-60 nm	50-200 ng/mL	MPs enter mitochondria and damage morphology and function; impair neural development and cause apoptosis	[61]
Endometrial organoids	Endometrial epithelial gland cells	PS	2 μm	5 and 50 μg/mL	Apoptotic responses and disrupted growth pattern	[88]
Hepatobiliary organoids	Hepatic progenitor cells	PS	1 μm	2.5 μg/mL	Hepatotoxicity; hepatic metabolism dysregulation MPs were localized in the bile duct area	[89]
Intestinal organoids	HIMEC	PS	25 nm	0.67 μg/mL	No significant toxicity at 60 μg/mL; downregulated IFI6 (immunosuppressive and antiviral functions) expression	[90]
	HIMEC	PS	196 and 211 nm	100 μg/mL	Validate MPs exposure impaired intestinal stem cells via Notch and Wnt/β-catenin signaling pathway under OS conditions	[91]
	HIMEC	PS, PTFE, PMMA	100 nm	50 μg/mL	Metabolic toxicity of three MPs can be predicted using nontargeted metabolomics	[92]
	HIMEC	PS	135-141 nm	60 μg/mL	Benzo[a]pyrene co-exposure inhibit intestinal stem cells differentiation by OS pathway; Notch signaling pathway	[93]
	hiPSCs	PS	50 nm	10 and 100 μg/mL	MPs accumulation was positively correlated with exposure time and concentration; ROS	[94]
Kidney organoids	hiPSCs	PS	1 μm	2.5 μg/mL	Nephrotoxicity; MPs induce nephrotoxicity through DDIT4-mediated autophagy and apoptosis	[74]
	hiPSCs	PS	97.77 nm	200-800 μg/mL	Inhibitory effects of MPs on kidney organoids growth were concentration- and time-dependent	[95]
	hiPSCs	PS	1 μm	2.5 μg/mL	Lead to increased ROS and mitochondrial damage in nephron progenitors; induce glycolysis inhibition contributing to nephrogenesis disruption	[96]
	hiPSCs	PS	1 μm	10 μg/mL	Nephrotoxicity; impair cell membrane integrity, disturbed mitochondrial homeostasis; proliferation and apoptosis; Notch signaling	[72]
Liver organoids	hESC	PS	1-5 μm	50 particles/mL	Low-dose of aged MPs induced reductive stress with disrupted mitochondrial respiratory chain function	[97]
	hESC	PS	1 μm	20-200 ng/mL	Induce hepatic injury via ferroptosis; small size has high cytotoxicity	[98]
	hESC	PS	1 μm	50 ng/mL	Due to physical contact and damage to cells, PS-induced hepatotoxic effects may be more significant than BPA	[99]
Lung organoids	Lung tissues	PS	40 nm	100 μg/mL	PS-NPs facilitate sustained transitional cell presence and accumulation	[100]
	Lung tissues	Nylon	1-10 μm	1-100 μg/mL	MPs made by nylon inhibit developing airway organoids; inhibit Hoxa5 can restore organoid	[101]
Retinal organoids	hESC	PS	< 0.2 mm	0.01-1 mg/mL	Neurotoxicity of MPs; triphenyl phosphate co-exposure exerted higher neurotoxicity	[102]

MPs: Microplastics; hESC: Human embryonic stem cell; PS: Polystyrene; ERK: Extracellular signal-regulated kinase; MAPK: Mitogen-activated protein kinase; hPSCs: Human pluripotent stem cells; hiPSCs: Human induced pluripotent stem cells; HIMEC: Human intestinal microvascular endothelial cells; OS: Oxidative stress; PTFE: Polytetrafluoroethylene; PMMA: Polymethyl methacrylate; ROS: Reactive oxygen species; DDIT4: DNA damage inducible transcript 4; BPA: Bisphenol A; NPs: Nanoparticles; Hoxa5: Homeobox A5.