Human umbilical cord blood-derived mesenchymal stem cell therapy in experimental spinal cord injury: A systematic review and meta-analysis

Table 1 Characteristics and key methodological features of included studies

Ref.	Study	Species	Injury model	Functional scale	Randomization	Blinding	Sample size1	Cell dose (per injection)	Cell dose (total)	Route	Timing
Yin et al[43]	R1	Rat	Transection	BBB	Not described	NR	50	NS	NS	IL	Acute
Lee et al[44]3	R2	Dog	Compression	Tarlov	Yes	Yes	10	1 × 106	1 × 106	IL	Subacute
Zhang et al[45]	R3	Rat	Compression	BBB	Yes	NR	62	1 × 106	1 × 106	IV	Subacute
Lee et al[46]4	R4	Dog	Compression	BBB	NR	NR	10	1-2 × 106	1-3 × 106	IL	Subacute
Seo et al[47]	R5	Rat	Contusion	BBB	Yes	Yes	98	1 × 106	1 × 106	IV	Acute
Yang et al[19]5	R6	Rabbit	Compression	Reuter2	Not described	Yes	43	2 × 106	6 × 106	IV	Subacute

¹Sample size refers to the total number of animals used in each study. The meta‑analysis of functional recovery included only the treatment and control groups from these studies, totaling 132 animals.

²Reuter score was transformed from “lower-is-better” to “higher-is-better” for analysis.

³In study R2, to generate a single study-level effect size, the single-spot and multi-spot transplantation subgroups were pooled into a unified treatment group, and the corresponding control groups were pooled accordingly for the meta-analysis of functional recovery. The dose of 1 × 10⁶ represents the per‑injection dose used for the single‑spot subgroup, which served as the basis for the pooled analysis.

⁴In study R4, seven dogs received the initial injection: Four received 1 × 10⁶ cells and three received 2 × 10⁶ cells. Two of these seven dogs received a second injection at 8 weeks (1 × 10⁶ and 2 × 10⁶ cells, respectively). The reported dose ranges reflect this variability.

⁵In study R6, rabbits received three intravenous doses of 2 × 10⁶ cells each at 1, 4, and 7 days post-decompression (total 6 × 10⁶ cells).

NR: Not reported; BBB: Basso, Beattie, and Bresnahan; NS: Not specified (insufficient data to calculate absolute cell dose); IL: Intralesional; IV: Intravenous.

Table 2 GRADE evidence profile for human umbilical cord blood-derived mesenchymal stem cells therapy in experimental spinal cord injury

Outcome (population)	Study IDs (number of animals)	Effect estimate (95%CI)	I2	Certainty (GRADE)	Key limitations (reasons for downgrading)
Functional recovery
Rat (BBB scale)	R1, R3, R5 (102)	SMD 2.32 (-2.14 to 6.78)	91.4%	Low	Serious inconsistency (I2 > 80%), serious imprecision (wide CI crossing zero)
Canine	R2, R4 (16)	SMD 1.75 (1.21-2.28)	0%	Very low	Very serious imprecision (very small sample size, n = 16); serious risk of bias
Rabbit (Reuter)	R6 (14)	SMD 3.79 (2.04-5.54)	N/A	Very low	Very serious imprecision (very small sample size, n = 14); serious indirectness (scale transformation)
Safety
Mortality (all species)	R1, R2, R3, R4, R5, R6 (172)	RR 1.20 (0.60-2.40)	30%	Very low	Very serious imprecision (CI includes both appreciable harm and no difference), serious risk of bias (inadequate AE reporting)

Note: (1) For the Reuter score (originally lower-is-better), means were multiplied by -1 prior to analysis so that a positive standardized mean difference indicates a treatment benefit; (2) The “serious imprecision” rating reflects wide confidence intervals or small sample size, indicating uncertainty about the precise magnitude of the treatment effect; and (3) The “low” overall rating for functional recovery reflects serious inconsistency (I² = 81.8%) and serious imprecision. Risk of bias was not further downgraded because unclear judgments primarily reflected poor reporting rather than confirmed high risk. BBB: Basso, Beattie, and Bresnahan; CI: Confidence interval; SMD: Standardized mean difference; RR: Risk ratio; N/A: Not applicable; AE: Adverse event.