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Table 2 Summary of articles included in the systematic review

From: The application of stem cell sheets for neuronal regeneration after spinal cord injury: a systematic review of pre-clinical studies

Study

Type of stem cell/type of graft/donors/stem cells characterization/cell sheets characterization

Cell differentiation at application

Type of animals

Animal model

Study cohorts

Follow-up

Outcomes

Mi et al. 2023 a [22]

SHED/Xenogenous/exfoliated deciduous teeth of clinical patients (3 donors)/flow cytometry (CD 44, CD 73, CD 90, and CD 105), Differentiation assay (Osteoblastic and adipogenic differentiation)/H&E staining,

Immunofluorescence staining (collagen I, collagen III, nestin, S100, β3-tubulin, MAP2, CGRP, MBP)

Nerve induced differentiation

SD rats, 180–230 g, female, 8–10 weeks

Complete transection, T10

(1) SHED + iSHED group, n = 5; (2) SHED group, n = 5; (3) control SCI, n = 5; 4) sham, n = 5; total: 20

60 days

Locomotor function (BBB) + sensory function (Von Frey test) + axonal regeneration (IF staining) + adverse effects

Mi et al. 2023 b [25]

SHED/Xenogenous/exfoliated deciduous teeth of clinical patients (3 donors)/flow cytometry (CD 44, CD 73, CD 90, and CD 105), Differentiation assay (Osteoblastic and adipogenic differentiation) / H&E staining

Immunofluorescence staining (collagen I, collagen III, nestin, S100, β3-tubulin, MAP2, CGRP, MBP)

Neurodifferentiation induced by homogenate proteins of the spinal cord

SD rats, 180–230 g, female, 8–10 weeks

Complete transection, T10

(1) hp-SHED group, n = 5; (2) SHED suspension group, n = 5; (3) control SCI, n = 5; 4) sham, n = 5; total: 20

60 days

Locomotor function (BBB + Grip strength test) + sensory function (Von Frey test) + axonal regeneration (IF staining) + adverse effects

Chen et al. 2022 [26]

ADSCs/Allogenous/female SD rats, 250–300 g/differentiation assay (osteoblastic and adipogenic differentiation)/optical microscopy, scanning electron microscopy, transmission electron microscopy, two-photon excited fluorescence microscope

Undifferentiated

SD rats, female, 250–300 g

Complete transection, T10

(1) ADSC group, n = 12; (2) control SCI, n = 12; (3) sham group, n = 6;

total: 30

8 weeks

Axonal regeneration (H&E staining + IF

staining)

Li et al. 2022 [27]

BMSCs/allogenous/male C57BL/6 mice, 6–8 weeks/flow cytometry (CD29, 45, 90), optical microscope, differentiation assay (osteoblastic and adipogenic differentiation)/H&E staining, Fluorescence microscopy (PKH67)

Undifferentiated

C57BL/6 mice, 8w

Complete transection, T10

(1) NGF-overexpressing BMSC group, n = 8; (2) NC-overexpressing BMSC group, n = 8; (3) control SCI, n = 8; (4) sham group, n = 8; total: 32

8 weeks

Locomotor function (BBB) + axonal regeneration (H&E staining + Nissl staining + IHC staining)

Yamazaki et al. 2021 [28]

BMSCs/allogenous/green fluorescent protein-expressing transgenic SD rats, 10 weeks/not reported/ELISA (HGF)

Undifferentiated

SD rats, female, 10 weeks, 250–300 g

Compression, 30 g, 1 min, T6-7

(1) BMSC group, n = 20; (2) BMSC cell suspension intramedullary injection group, n = 20; (3) control SCI, n = 20; total: 60

7 weeks

Locomotor function (BBB) + sensory function (Von Frey test) + axonal regeneration (H&E staining + LFB staining + IF staining)

Fan et al. 2020 [29]

BMSCs/xenogenous/Chinese big-ear white rabbits, Male and female, 180–200 g, 2 weeks/differentiation assay (osteoblastic, adipogenic, and neurogenic differentiation), Immunofluorescence staining (CD 29, CD 44, and CD 90)/scanning electron microscope, Immunofluorescence staining (collagen I, fibronectin, CD31), uniaxial tensile testing

Undifferentiated

SD rats, female, 200 g

Complete transection, T9

(1) BMSC + HUVEC group, n = 20; (2) BMSC group, n = 20; (3) control SCI, n = 20; total: 60

8 weeks

Locomotor function (BBB) + axonal regeneration (H&E staining + LFB staining + IF staining) + adverse effects

Okuda et al. 2017 [30]

BMSCs/allogenous/Fischer 344 rats, female, 7 weeks/not reported/cell viability assay

Undifferentiated

Fischer 344 rats, female, 8 weeks

Complete transection, T10

(1) BMSC group, n = 9; (2) control SCI, n = 9; total: 18

8w

Locomotor function (BBB) + axonal regeneration (IF staining)

  1. Abbreviations: ADSCs Adipose-derived mesenchymal stem cells, BBB Basso-Beattie-Bresnahan scale, BMSCs Bone marrow mesenchymal stem cells, CD Clusters of differentiation, CGRP Calcitonin gene-related peptide, ELISA Enzyme-linked immunosorbent assay, H&E Hematoxylin/eosin, HGF Hepatocyte growth factor, HUVEC Human umbilical vein endothelial cell, IF Immunofluorescence, IHC Immunohistochemistry, LFB Luxol fast blue, MAP2 Microtubule-associated protein 2, MBP Myelin basic protein, NGF Nerve Growth factor, SD Sprague–Dawley, SCI Spinal cord injury, SHED Stem cells from human exfoliated deciduous teeth, iSHED neural-induced SHED, hp-SHED SHED induced with induced with homogenate protein of spinal cord