Stem cell homing, tracking and therapeutic efficiency evaluation for stroke treatment using nanoparticles: A systematic review

Table 4 Stem cell labeling process

Ref.	Cells	Passage	Contrast agent	Concen-tration μg/mL)	Incu-bation time (h)	Strategy of interna-lization	Effici-ency	Quantification			Cellular viability		Others analysis
								(pgFe/cell)	Technique		Method	Results
Lim et al[33]	MSC	P5-P7	NP(BCN-Fe3O4)	300	2	Ac4ManNAz	98.7%	15.3	ICP-MS		CCK-8 assay	> 95%	CF, SEM, CEM, MRI
Wang et al[29]	MSC	P2-P7	Alkyl-SPIO	an appropriate amount of Alkyl-PEI/SPIO (N/P = 20)	6	PEI	High Eff.	NA	NA		CCK-8 assay	> 90%	BLI, MRI
Yun et al[30]	NSC	NR	ZnMNP	50	NR	PLL: 1.5 g/mL	NR	4.6	NR		NA	NA	TEM, BLI
Argibay et al[38]	MSC	P0-P2, P9, P17	Fe3O4	100	24	PLL: 1.5 μg/mL	High Eff.	0.9-7.7	ICP-OES		LDH assay	NSD	TEM
Duan et al[37]	MSC	P3-P5	Fe3O4-LCP	15	1.5	PEI	Approximately 100%	Approximately 9	AAS		CCK-8 assay	> 90%	TEM, MRI
Lu et al[35]	NPC	NR	C-NP	10	4	PLL and Lipofectamin	Approximately 99.3%	NA	NA		CCK-8 assay	> 95%	MRI, VFL
			N-NP				Approximately 8.7%
Zhang et al[34]	NSC	P2-P3	Ferritin	MOI: 10	24	PLL	Approximately 63%	3.5	AAS		CCK-8 assay	NSD	TEM, MRI, PB
Lin et al[36]	MSC	P5-P9	ASP-SPION	30	1	NA	Approximately 100%	2.68	AAS		CCK-8 assay	> 90%	MRI, TEM
Zhang et al[39]	NSC	NR	Anti-CD15-SPION	NR	NR	NA	NR	NA	NA		NA	NA	NA
Duan et al[40]	MSC	P3-P5	Fe3O4-LCP	15	1.5	PEI	LCP > PLL	8.373	AAS		CCK-8 assay	> 90%	TEM, in vitro MRI
			Fe3O4	25	24	PLL		9.214
Bai et al[42]	MSC	NR	bCD-Gd	2 μmol	24	PLL	NR	NA	NA		NA	NA	NA
Chen et al[28]	MSC	NR	GRMNB	10	2	NR	High Eff.	33.62	AAS		MTT	87.6	BLI
Tan et al[41]	MSC	NR	Ferucarbotran	NR	24	NA	Approximately 95%	NA	NA		NA	NA	NA
Janowski et al[44]	NSC	NR	Fe3O4	25	48	PLL: 375 ng/mL	NR	NA	NA		NI	NI	NA
Park et al[43]	MSC	NR	PCION	1	0.25	PLL, EMF	NR	NA	NA		NA	NA	TEM, MRI
Zhang et al[45]	NPC	NA	fmNP	5, 10, 20, 33	0.5, 1, 2, 3	NA	fmNP > fdNP	5-30	ICP-AES		CCK-8 assay	90%-98%	TB
			fdNP					1-2.5			NA	NA	NA
Tarulli et al[46]	MSC	NR	MPIO	18.8	24	NA	95%	54	Flow cytometry		Flow cytometry	Approximately 94%	CF
Liu et al[47]	NSC	NR	SPION	14	24	NA	NR	NR	NR		NI	NI	NA
Wang et al[48]	MSC	NR	PMNC	0.5 mmol	1	NA	Approximately 100%	16-20	ICP-OES		CCK-8 assay	> 95%	TEM, CF, MRI
Lee et al[50]	MSC	P5, P6	MGIO	50	24	NA	Approximately 97%	33.3	ICP-OES		NI	> 95%	TEM, microarray
Song et al[49]	NPC	NR	Feridex	112.4	72	NA	Approximately 100%	0.2	AAS		TB	Unaffected	MRI
Kim et al[51]	MSC	NR	Feridex	1	12-16	PS	NR	2.6	ICP/MS		NI	NI	NA
Guzman et al[52]	NSC	NR	Feridex	5	24	PS: 2.5 μg/mL	98%	Halved every 3 d (%)	Semiquantitative (MRI)		Cell counting	Approximately 92%	NA
Syková et al[53]	MSC, rOEC	NR	Endorem	112.4	48-72	NA	NR	NA		NA	NA	NA	TEM
Zhu et al[54]	NSC	NR	Feridex	NR	1	Effectene	High Eff.	NA		NA	NR	NI	NA

MSC: Mesenchymal stem cells; NSC: Neural stem cells; ESC: Embryonic stem cell; rOEC: Rat olfactory ensheathing cells; P: Passage; NR: No reported; NA: Not applicable; NP: Nanoparticle; BCN: Bicyclo[6.1.0]nonyne; Fe₃O₄: Magnetite; SPIO: Superparamagnetic iron oxide; ZnMNPs: Zinc-doped ferrite magnetic nanoparticles; LCP: Loaded cationic polymersomes; C-NP: Cationic nanoparticle; N-NP: Neutral nanoparticle; ASP: Spermine-modified amylose; SPION: Superparamagnetic iron oxide nanoparticle; bCD-Gd: Bacterial cytosine deaminase-gadolinium; GRMNB: Gold nanorods crystal-seeded magnetic mesoporous silica nanobeads; MOI: Multiplicities of infection; PCION: Poly-(ethylene glycol)-coated cross-linked iron oxide nanoparticles; fmNP: FmSiO4@SPIONs; fdNP: FdSiO4@SPIONs; MPIO: Micron-sized superparamagnetic iron oxide particles; PMNC: Polystyrene magnetite nanocluster; MGIO: Microgel iron oxide; Alkyl-PEI: Amphiphilic low molecular weight polyethylenimine; MOI: Multiplicities of infection; Ac4ManNAz: Tetraacetylated N-azidoacetyl-D-mannosamine; PEI: Polyethylenimine; PLL: Poly-L-Lysine; EMF: External magnetic field; PS: Protamine sulfate; High Eff.: Hight efficiency; LCP: Loaded cationic polymersomes; AAS: Atomic absorption spectrophotometer; CCK-8: Cell counting kit-8; LDH: Lactate dehydrogenase; MTT: 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide; TB: Turnbull blue; NSD: No significant differences; CF: Confocal fluorescence; SEM: Scanning electron microscope; CEM: Cryoelectron microscope; MRI: Magnetic resonance image; BLI: Bioluminescence image; TEM: Transmission electron microscopy; VFL: Visible field fluorescence; PB: Prussian blue.