Evaluation of the Efficacy of Stem Cell Therapy in Animal Models of Intervertebral Disc Degeneration Based on Imaging Indicators: A Systematic Review and Meta-Analysis

Table 1

Characteristics of the studies included.

Author	Year	Country	Study type	Animal	Modeling method	Types of stem cells	Source of stem cells	Injection dose	Control	Observation time	Imaging-based evaluation indicators
Friedmann et al. [1]	2021	Germany	RCT	Merino sheep, female	Nucleotomy	ADSCs+collagen hydrogel	Sheep		Not provided	12 months	Disc height
Schmitt et al. [8]	2021	Germany	RCT	Merino sheep, female	Nucleotomy	ADSCs+chitosan carboxymethyl cellulose hydrogel scaffold	Sheep		Not provided	12 months	Disc height
Choi et al. (1) [9]	2020	Korea	RCT	Sprague-Dawley rats, female	Needle puncture	WJ-MSCs+HAMC	Human		PBS	6 weeks	MRI index
Choi et al. (2) [9]						WJ-MSCs
Xiao et al. (1) [10]	2020	China	RCT	Mice	Needle puncture	Sod2-ADSCs	Human		Not provided	8 weeks	DHI; MRI index; T2 signal intensity
Xiao et al. (2) [10]						Cat-ADSCs
Xiao et al. (3) [10]						Null-ADSCs
Xiao et al. (4) [10]						ADSCs
Yan et al. (1) [15]	2019	China	RCT	New Zealand white rabbits	Nucleus pulposus aspiration	BMSCs+SAB	Rabbits		PBS	8 weeks	T2 signal intensity
Yan et al. (2) [15]						BMSCs
Ma et al. (1) [16]	2018	China	RCT	New Zealand white rabbits	Needle puncture	ADSCs+PRP	Human		PBS	4 weeks	MRI signal score
Ma et al. (2) [16]						ADSCs
Zhou et al. (1) [17]	2018	China	RCT	New Zealand white rabbits	Needle puncture	ADSCs+NPCS	Human		Not provided	16 weeks	DHI; MRI index
Zhou et al. (2) [17]						ADSCs
Ishiguro et al. [18]	2018	Japan	RCT	Sprague-Dawley rats, male	Nucleotomy	ADSCs+TEC	Rats		NP reimplantation	6 months	DHI; Endplate degeneration score
Hussain et al. [19]	2018	United States	RCT	Finn sheep	Nucleotomy	BMSCs+HDC	Sheep	2.5 × 10^5	HDC	6 weeks	DHI; Pfirrmann grade; NP mid-sectional volume; NP T2 relaxation time
Zhu et al. (1) [20]	2018	China	RCT	Sprague-Dawley rats, male	Needle puncture	ADSCs+PEAD+GDF5	Human	Not provided	PEAD+; GDF5	24 weeks	DHI; MRI index; T2 signal intensity
Zhu et al. (2) [20]						ADSCs+GDF5
Lykov et al. (1) [21]	2018	Russia	RCT	Wistar rats, male	Needle puncture	BMSCs+EPO	Rats		Not provided	3 weeks	Disc height
Lykov et al. (2) [21]						BMSCs
Li et al. [22]	2016	China	RCT	New Zealand white rabbits	Nucleotomy	BMSCs+DSP	Rabbits		DSP	12 weeks	DHI
Wang et al. [23]	2015	China	RCT	New Zealand white rabbits, male	Needle puncture	BMSCs+PRP	Sheep		PRP	8 weeks	MRI signal score
Chen et al. [24]	2015	China	RCT	New Zealand white rabbits, male	Nucleus pulposus aspiration	NPSCs	Human		NPCs	2 months	DHI; T2 signal intensity
Wang et al. (1) [25]	2014	China	RCT	New Zealand white rabbits	Nucleus pulposus aspiration	BMSCs+AFCs	Rabbits	Not provided	Saline	2 weeks	Disc height ratio; Pfirrmann grade
Wang et al. (2) [25]						BMSCs
Freeman et al. (1) [26]	2014	Australia	RCT	Merino wether sheep	Nucleotomy	BMSCs into AF	Sheep		PBS	12 months	DHI; Disc height; Pfirrmann grade
Freeman et al. (2) [26]						BMSCs into NP
Cai et al. [27]	2014	China	RCT	New Zealand white rabbits	Needle puncture	BMSCs	Rabbits		PBS	10 weeks	T2 signal intensity; T2 relaxation time; DHI
Yi et al. (1) [28]	2013	China	RCT	New Zealand white rabbits	Needle puncture	TIMP1-BMSCs	Rabbits		PBS	12 weeks	DHI
Yi et al. (2) [28]						BMSCs
Feng et al. [29]	2010	China	RCT	New Zealand white rabbits	Nucleus pulposus aspiration	BMSCs	Rabbits		NPCs	16 weeks	DHI; T2 signal intensity
Jeong et al. [30]	2010	Korea	RCT	Sprague-Dawley rats, female	Needle puncture	ADSCs	Human		Saline	6 weeks	Disc height; T2 signal intensity
Yang et al. [31]	2009	China	RCT	New Zealand white rabbits	Nucleus pulposus aspiration	BMSCs+PFG-TGF-b1	Rabbits		PFG-TGF-b1	12 weeks	DHI
Sakai et al. [32]	2005	Japan	RCT	New Zealand white rabbits	Nucleus pulposus aspiration	BMSCs	Rabbits		Atelocollagen	24 weeks	T2 signal intensity; DHI

WJ-MSCs: Wharton’s jelly-derived mesenchymal stromal cells; HAMC: hyaluronan–methylcellulose; PBS: phosphate-buffered saline; BMSCs: bone marrow-derived mesenchymal stem cells; AFCs: annulus fibrosus cells; ADSCs: adipose-derived mesenchymal stem cells; PRP: platelet-rich plasma; DSP: dexamethasone sodium phosphate; NP: nucleus pulposus; AF: annulus fibrosus; NPCS: decellularized nucleus pulposus-based cell delivery system; TEC: scaffold-free tissue-engineered construct; HDC: riboflavin cross-linked high-density collagen gel; DHI: disc height index; SAB: salvianolic acid B; Ad-null: ADSCs transduced with an adenovirus vector containing no transgene expression cassette; Ad-Sod2: ADSCs transduced with recombinant adenovirus Sod2; Ad-Cat: ADSCs transduced with recombinant adenovirus Cat; PEAD: a growth factor delivery vehicle composed of heparin and the synthetic polycation poly(ethylene argininylaspartate diglyceride); GDF5: growth and differentiation factor-5; NPSCs: Nucleus pulposus-derived stem cells; PFG-TGF-b1: pure fibrinous gelatin-transforming growth factor-b1; EPO: erythropoietin; TIMP: tissue inhibitor of metalloproteinases.