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

Table 10 Stem cell administration, homing and cellular therapeutic efficiency

Ref.	Cell Type	Immuno-genicity	Time from stroke (h)	Cell administration			Groups	Follow-up	Outcome
				Route	Number	Volume (µL)			Behavior	Infarct volume	Mole-cular proteins/others	Cells mi-gration
Lim et al[33]	MSC	XNG	NR	IC-CTL	1 × 106	5	Stroke + cells vs Stroke-cells	1, 3, 7, 10, 14 d	NR	(+)	NR	(+)
Wang et al[29]	MSC	XNG	24	ITC1	5 × 105	100	Alkyl-SPIO/siPHD2 > Alkyl-SPIO/si	1, 3, 7 d	(+) mNSS; FFT at 14 d	(+) 7 d	(+) Ki67; CD31 -7 d; (+) NeuN -14 d	(+)
	MSC	XNG	24	ITC1	5 × 105	100	Alkyl-SPIO/si vs saline	1, 3, 7 d	(+) mNSS; FFT at 14 d	(-) 7 d	(+) Ki67; CD31 -7 d; (+) NeuN -14 d	(+)
Yun et al[30]	NSC	XNG	24	IA-IC	3 × 106	100	Mag-Cells > UL-Cells/sa-line	0, 3, 5, 7, 21 d	(+) Cilinder at 21d	NR	(+) MAP2; Nestin; GFAP; TuJ1 -7d	(+)
Argibay et al[38]	MSC	ALG	8	IA; IV-jugular	2 × 105; 1 × 106	300	D-MNP-labeled MSC (IA × IV)	4, 24, 72 h	(-) Cilinder	(-) at 14d	(-) CD31; Ki67; DCX	(+)
Duan et al[37]	MSC	ALG	48	IC-CTL	5 × 105	3	Labeled cell > UL-cells	1, 2, 3, 4, 6, 8 wk	(-) mNSS	(-)	(-) TUNNEL (-) GFP	(+)
							Labeled/UL vs control	1, 2, 3, 4, 6, 8 wk	(+) mNSS at 3, 4, 6, 8 wk	(+) at 4, 6, 8 wk	(+) TUNNEL 7-21 d, (+) GFP 7-21 d	(+)
Lu et al[35]	NPC	ALG	NR	IC-IPS	5 × 105	2.5	labeling with N-NPS	0, 3, 7, 14 d	NR	(+)	(+) Nestin	(+) low
							labeling with C-NP	0, 3, 7, 14 d	NR	(+)	(+) Nestin	(+)
Zhang et al[34]	NSC	XNG	48	IC-CTL	5 × 105	3	FTH-EGFP-NSC > non trans-ducec NSC	1, 2, 3, 4, 5, 6 wk	(+) mNSS at 1-6 wk	(+) at 1-6 wk	(+) GFAP; Nestin; CD11b at 6 wk	(+)
Lin et al[36]	MSC	ALG	48	IC-CTL	5 × 105	NR	ASP-SPION vs UL vs PBS	1, 2, 3, 4, 5, 6 wk	(-) mNSS	(-)	(-) GFAP; NeuN; CD11	(+)
Zhang et al[39]	NSC	XNG	7d	IC-CTL	NR	7	Stroke pure > Stroke + Ara-C	0, 2, 8 d	NR	(+) at 8 d	(+) CD15+; Nestin at 8 d	(+)
Duan et al[40]	MSC	ALG	48	IC-CTL	5 × 105	3	PLL-SPION or PM > UL	1, 2, 3, 4, 5, 6 wk	NR	(+) at 4, 6 wk	(-) GFP	(+)
Bai et al[42]	MSC	XNG	24	IA - IC	1 × 106	100	DM + RWJ + cell > DM + cells	1, 3, 5, 7, 10, 14 d	NR	(+)	(+) p38 MAPK at 7 d	(+)2
Chen et al[28]	MSC	XNG	30 min	IV-femoral	5 × 105		Mag-cells > UL-cells	0, 3, 7, 14 d	(+) VM at 14, 28 d	(+) at 14 d	(+) TuJ1; NeuN; GFAP at 28 d; (+) RT-PCR1 at 28 d	(+)
Tan et al[41]	MSC	ALG	7 d	IC-CTL	5 × 105	10	Stroke + cells over time	0, 1, 7, 14, 21, 42 d	NR	NR	(-) GFP and NeuN at 7 d; (+) GFP and NeuN at 6 wk	(+)
Janowski et al[44]	NSC	AuTL	NR	IC	2 × 104	10	Case over time	0, 1, 7, 60, 120 d, 33 mo	NR	NR	NR	(+)
Park et al[43]	MSC	XNG	14d	IC-CTL	6 × 105	5	Pcion/pDNA MSC vs control	1, 2 d	NR	(-)	NR	(+)
Zhang et al[45]	NPC	ALG	24	IC-CTL	5 × 105	5	fsiSPION-NPC vs control	1, 3 d	NR	(+)	(+) Nestin	(+)2
	NPC	ALG	24	IV-tail	1 × 106	300	fsiSPION-NPC vs control	1, 3 d	NR	NR	(+) Nestin	(+)
Tarulli et al[46]	MSC	XNG	72	IV-tail	3 × 106	700	MPIO-BMSC vs UL-BMSC	1, 7, 14 d	NR	NR	NR	(+)
Liu et al[47]	NSC	XNG	NR	IC-CTL	3 × 104	5	Stroke + NSC_FA > Stroke + NSC	1, 7 d	NR	NR	(+) Sox-2 BrdU at 21 d	(+)
Wang et al[48]	MSC	XNG	7d	IC-CTL	1 × 105	5	FMNC-MSC > UL-MSC vs control (FMNC)	0, 1, 7, 30 d	NR	NR	(+) TuJ1	(+)
Lee et al[50]	MSC	XNG	48	IC-CTL	2 × 104	5	M600-MSC vs FC-MSC	1, 5, 12 d	NR	NR	NR	(+)
	MSC	XNG	48	IV-tail	2 × 106	500	M600-MSC vs control	5, 12 d	NR	NR	NR	(+)
Song et al[49]	NPC	XNG	24	IC-IPS	4 × 105	5	FO-NPC vs control	1, 3, 7, 14, 21, 28 d	NR	NR	(+) BrdU; GFAP at 28 d	(+)
	NPC	XNG	24	IV-tail	4 × 106	500	FO-NPC vs control	1, 3, 7, 14, 21, 28 d	NR	NR	(+) BrdU; GFAP at 28 d	(+)
Kim et al[51]	MSC	AuTL	7d	IC-IPS/CTL	1 × 105	2	Feridex®-labeled hMSC over time for both vias	2d, 1, 2, 4, 6, 8, 10 wk	NR	NR	(-) GFAP; TH; MAP2; TuJ1; Nestin at 10 wk	(+)
Guzman et al[52]	NSC	XNG	7d	IC-CTL	3 × 105/5 × 104		NSC-SCns-SPION	3, 9, 12,18 wk	NR	NR	(+) SC121 or SC101; TuJ1; GFAP; MAP2 at 18 wk	(+)
Syková et al[53]	rOEC	ALG	NR	IC-CTL	NR	NR	OEC-SPION over time	3-7 wk	NR	NR	(+) NeuN; GFAP at 28 d	(+)
	MSC	XNG	NR	IV-femoral	NR	NR	MSC over time	6-30 d	NR	NR	(+) NeuN; GFAP at 28 d	(+)
Zhu et al[54]	NSC	AuTL	NR	IC	NR	NR	Patients treat with NSC and no treat	2 yr	(+) SEP and DRS at 6, 9 mo	(+) cells uptake by PET at 3, 6 mo	NI	(+)

¹left ventricle.

²In addition to cell migration analysis, studies reported biodistribution analysis after stem cell administration. The Bay study[42] reported biodistribution in the liver, spleen, heart, lungs, and kidneys; Zhang et al[45] reported that the SPION-labelled cells IV > IA at 3 d after injection were detected in spleen, liver, heart, kidney, and lung. MSC: Mesenchymal stem cells; NSC: Neural stem cells; ESC: Embryonic stem cell; rOEC: Rat olfactory ensheathing cells; NR: No reported; XNG: Xenogeneic; ALG: Allogeneic; AuTL: Autologous; IC: Intracerebral; IC-CTL: IC contralateral; ITC: Intracardially; IC-IPS: IC ipsilateral; IV: intravenous; IA-IC: Intraarterial through internal carotid artery; Alkyl-SPIO: Amphiphilic low molecular weight superparamagnetic iron oxide; Mag: External magnet; UL: Unlabeled; siPHD2: siRNA against PHD2; C-NP: Cationic nanoparticle; N-NP: Neutral nanoparticle; FTH-eGFP: ferritin heavy chain: Enhanced green fluorescent protein; ASP-SPION: Spermine-modified amylose superparamagnetic iron oxide nanoparticle; FBS: Fetal bovine serum; Ara-C: Cytosine arabinosine; PLL: Poly-L-Lysine; PM: Polymersone; PCION: Poly-(ethylene glycol)-coated cross-linked iron oxide nanoparticles; MPIO: Micron-sized superparamagnetic iron oxide particles; DM: Diabetes mellitus; RWJ: RWJ67657; fsiSPION: fmSiO4@SPION; FC: Ferucarbotran; FA: Folic acid; FO: Ferumoxide; FMNC: Fluorescent-magnetite-nanocluster; mNSS: Modified neurological severity score; FFT: Foot-faults test; VM: Vertical movement; SEP: Somatosensory evoked potential; DRS: Disability rating scale; MAP2: Microtubule-associated protein 2; GFAP: Glial fibrillary acidic protein; TuJ1: Neuron-specific class III beta-tubulin; GFP: Green fluorescent protein; MAPK: Mitogen-activated protein kinase; RT-PCR: Reverse transcription polymerase chain reaction; BrdU: 5′-Bromo-2′-deoxyuridine; TH: Tyrosine hydroxylase.