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Is cell transplantation a reliable therapeutic strategy for spinal cord injury in clinical practice? A systematic review and meta-analysis from 22 clinical controlled trials

  • He Zhao
  • Qing-Ling Sun
  • Li-Jun Duan
  • Yong-Dong Yang
  • Yu-Shan Gao
  • Ding-Yan Zhao
  • Yang Xiong
  • He-Jun Wang
  • Jia-Wei Song
  • Kai-Tan Yang
  • Xiu-Mei WangEmail author
  • Xing YuEmail author
Review Article

Abstract

Purpose

It is an open question whether cell transplantation can provide safety and effective outcome to spinal cord injury (SCI) patient which has remained controversial for almost 40 years. This study aimed to evaluate the safety and efficacy of cell transplantation in SCI patients.

Method

Studies of the cell transplantation for SCI were retrieved from PubMed, Embase, Medline, Cochrane Library and analyzed quantitative data by Review Manager 5.3.

Results

Twenty-one clinical controlled studies with 973 patients were included. The pooled results suggested that cell transplantation significantly improved ASIA score, ASIA motor score, ASIA sensory score, Barthel Index score, residual urine volume, rehabilitative time of automatic micturition. Furthermore, subgroup analysis indicated that the stem cells exhibited more potent than the non-stem cells in spinal cord repair. Cell transplantation at more than 14 days after injury showed more significant improvements than that within 14 days from injury. The dosage of cell transplantation between 1–5 × 107 and 10–20 × 107 was the potent quantity for the patient with SCI. Intrathecal injection and intravenous + intrathecal injection showed more superior to the other method. The top 5 adverse events were febrile reaction (11.5%), neurologic pain (11.3%), headache (2.6%), neurologic deterioration (2.4%), and rigidity or spasticity (1.6%).

Conclusion

Cell transplantation appears to be a safe therapeutic strategy possessing substantial beneficial effects in the patients with SCI in clinic. Moreover, treating SCI with stem cell, the dosage of cells between 1–5 × 107 and 10–20 × 107, in intermediate or chronic phase, minimally invasive techniques, may bring more advantage to SCI patient.

Graphical abstract

These slides can be retrieved under Electronic Supplementary Material.

Keywords

Cell transplantation Spinal cord injury Systematic review and meta-analysis 

Abbreviations

ADSCs

Adipose-derived stem cells

BMSCs

Bone mesenchymal stem cell

MMCs

Marrow mononuclear cells

UCMSCs

Umbilical cord-derived mesenchymal stem cells

OECs

Olfactory ensheathing cells

AIM

Autologous incubated macrophage

SCs

Schwann cells

OLP

Olfactory lamina propria

GM-CSF

Granulocyte-macrophage colony-stimulating factor

FB-DNS/PCs

Fetal brain-derived neural stem/progenitor cell

CNS

Central nervous system

Notes

Acknowledgments

Thank you so much for contributions made by all members of Pro. Xiu-Mei Wang`s group (School of Materials Science and Engineering, Tsinghua University). Thank you so much for contributions made by all members in department of orthopedics III (Dongzhimen Hospital, Beijing University of Chinese Medicine). Thank you so much for contributions made by Dr. Feng-He (China Academy of Chinese Medical Science), Dr. Wan-Jie Gu (Drum Tower, Medical College of Nanjing University), Dr. Yun-Tao Zhao(Aerospace Center Hospital, Peking University).

Author contributions

HZ, XMW, and XY designed the systematic review. HZ and QLS drafted the protocol, and LJD, YDY, YSG, and DYZ revised the manuscript. YX and HJW will independently screen the potential studies, extract data, assess the risk of bias, and finish data synthesis. JWS and KTY will arbitrate any disagreements during the review. All authors approved the publication of the manuscript.

Funding

This work was funded by the National Twelfth Five-Year Plan for Science and Technology Support (Grant No. 2012BAI18B05).

Compliance with ethical standards

Conflict of interest

Authors declare that they have no conflict of interest.

Supplementary material

586_2019_5882_MOESM1_ESM.tif (1.3 mb)
Supplement 1 ASIA subgroup stem cell VS. non-stem cell (TIFF 1367 kb)
586_2019_5882_MOESM2_ESM.tif (1.5 mb)
Supplement 2 ASIA subgroup phase (TIFF 1520 kb)
586_2019_5882_MOESM3_ESM.tif (1.6 mb)
Supplement 3 ASIA subgroup cell number (TIFF 1630 kb)
586_2019_5882_MOESM4_ESM.tif (1.5 mb)
Supplement 4 ASIA motion subgroup stem cell VS. non-stem cell (TIFF 1488 kb)
586_2019_5882_MOESM5_ESM.tif (1.6 mb)
Supplement 5 ASIA motion subgroup phase (TIFF 1618 kb)
586_2019_5882_MOESM6_ESM.tif (1.7 mb)
Supplement 6 ASIA motion subgroup cell number (TIFF 1723 kb)
586_2019_5882_MOESM7_ESM.tif (1.5 mb)
Supplement 7 ASIA sensation subgroup stem cell VS. non-stem cell (TIFF 1497 kb)
586_2019_5882_MOESM8_ESM.tif (1.6 mb)
Supplement 8 ASIA sensation subgroup phase (TIFF 1635 kb)
586_2019_5882_MOESM9_ESM.tif (1.7 mb)
Supplement 9 ASIA sensation subgroup cell number (TIFF 1742 kb)
586_2019_5882_MOESM10_ESM.tiff (1.6 mb)
Supplement 10 ASIA subgroup cell transplantation techniques (TIFF 1632 kb)
586_2019_5882_MOESM11_ESM.tif (2.1 mb)
Supplement 11 ASIA motion subgroup cell transplantation techniques (TIFF 2174 kb)
586_2019_5882_MOESM12_ESM.tif (2.2 mb)
Supplement 12 ASIA sensation subgroup cell transplantation techniques (TIFF 2215 kb)
586_2019_5882_MOESM13_ESM.tif (1.1 mb)
Supplement 13 Sensitive analysis of cell transplantation techniques in ASIA score (TIFF 1176 kb)
586_2019_5882_MOESM14_ESM.tif (1.2 mb)
Supplement 14 Sensitive analysis of cell transplantation techniques in ASIA motion (TIFF 1250 kb)
586_2019_5882_MOESM15_ESM.tif (1.2 mb)
Supplement 15 Sensitive analysis of cell transplantation techniques in ASIA sensation (TIFF 1263 kb)
586_2019_5882_MOESM16_ESM.tif (854 kb)
Supplement 16 Barthal Index subgroup stem cell VS. non-stem cell (TIFF 853 kb)
586_2019_5882_MOESM17_ESM.tif (856 kb)
Supplement 17 Barthal Index subgroup phase (TIFF 855 kb)
586_2019_5882_MOESM18_ESM.tif (1.2 mb)
Supplement 18 Barthal Index subgroup cell number (TIFF 1211 kb)
586_2019_5882_MOESM19_ESM.tif (615 kb)
Supplement 19 Residental urinal subgroup stem cell VS. non-stem cell (TIFF 615 kb)
586_2019_5882_MOESM20_ESM.tif (679 kb)
Supplement 20 Rehabilitative time of automatic micturition subgroup stem cell VS. non-stem cell (TIFF 678 kb)
586_2019_5882_MOESM21_ESM.pptx (1.1 mb)
Supplementary material 21 (PPTX 1176 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • He Zhao
    • 1
    • 3
  • Qing-Ling Sun
    • 2
  • Li-Jun Duan
    • 3
    • 5
  • Yong-Dong Yang
    • 3
  • Yu-Shan Gao
    • 4
  • Ding-Yan Zhao
    • 3
  • Yang Xiong
    • 3
  • He-Jun Wang
    • 3
  • Jia-Wei Song
    • 3
  • Kai-Tan Yang
    • 3
  • Xiu-Mei Wang
    • 1
    Email author
  • Xing Yu
    • 3
    Email author
  1. 1.School of Materials Science and EngineeringTsinghua UniversityBeijingChina
  2. 2.Department of Geriatric, Dongzhimen HospitalBeijing University of Chinese MedicineBeijingChina
  3. 3.Department of Orthopedics III, Dongzhimen HospitalBeijing University of Chinese MedicineBeijingChina
  4. 4.Department of Basic Medical SciencesBeijing University of Chinese MedicineBeijingChina
  5. 5.Department of OrthopedicsBayannaoer City HospitalBayannaoer CityChina

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