Table 1. Characteristics of included studies.
Stem cells | Animal models | Stem cell application | Results of stem cell application | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Study | Donor | Type | Source | Animal | Lesion Induction | Timing of lesion induction | Dosage | Timing of transplantation | Vehicle | Timing of evaluation | Animal survival | Defect coverage | Spinal cord changes |
Lee, 2004(30) | Human | ESCs | Blastocyst | Chicken embryo | Surgical creation | HH18-19 | 2 × 104 cells/amniotic cavity | HH18-19; immediately after surgical creation | Intra-amniotic injection | HH 28, 30 and 35 | Yes | Yes | No |
Lee, 2006(31) | Human | ESCs | Blastocyst | Chicken embryo | Surgical creation | HH18-19 | 4 × 104 cells/amniotic cavity | HH18-19; immediately after surgical creation | Intra-amniotic injection | HH 30, 35 and 40 | Yes | Yes | No |
Lee, 2010(32) | Human | NSCs and MSCs | Fetal NCSCs, telencephalon (GA 14-18w); fetal MSCs, spinal BM (GA 12-l5w) | Chicken embryo | Surgical creation | HH18-19 | 2 × 104 cells/amniotic cavity | HH18-19; immediately after surgical creation | Intra-amniotic injection | HH 28, 30 and 35 | Yes | Yes | No |
Li. 2012(33) | Adult Wistar rat | MSCs | Bone marrow | Wistar rat | Retinoic acid(140 mg/kg) | E10 | 1.4-7 ×103 cells/spinal cord | E16-18 | Direct spinal cord injection | E20 | Yes | No | No |
Li. 2014(34) | Adult Wistar rat | MSCs | Bone marrow | Wistar rat | Retinoic acid(140 mg/kg) | E10 | 6-10 × 103 cells/spinal cord | E16 | Direct spinal cord injection | E20 | No | No | Yes |
Ma. 2015(35) | Adult Wistar rat | MSCs | Bone marrow | Wistar rat | Retinoic acid(140 mg/kg) | E10 | 6-10 × 103 cells/spinal cord | E16 | Direct spinal cord injection | E20 | Yes | No | Yes |
Li. 2016(30) | Adult Wistar rat | MSCs | Bone marrow | Wistar rat | Retinoic acid (140 mg/kg) | E10 | 2 × 107 cells/spinal cord | E16 | Chitosan-gelatin scaffold | E20 | Yes | Yes | No |
Wei. 2020a(37) | Adult Wistar rat | MSCs | Bone marrow | Wistar rat | Retinoic acid(140 mg/kg) | E10 | 4 - 6 x 106 cells/uterine cavity | E16 | Intra-amniotic injection and | E2l | Yes | Yes | No |
Wei. 2020b(38) | Adult Wistar rat | MSCs | Bone marrow | Wistar rat | Retinoic acid(140 mg/kg) | E10 | 5 × 106 cells/uterine cavity | E15 | Ex vivo intra-amniotic injection | E20 | Yes | Yes | Yes |
Dionigi. 2015a(39) | Normal Lewis ratfetus | MSCs | Amniotic fluid(E21) | Sprague-Dawley rat | Retinoic acid (60 mg/kg) | E10 | 1 × 105 cells/uterine cavity | E17 | Intra-amniotic injection | E21 | Yes | Yes | No |
Dionigi. 2015b(40) | Normal Lewis rat fetus | MSCs | Amniotic fluid (E21) | Sprague-Dawley rat | Retinoic acid (60 mg/kg) | E10 | 1 × 105 cells/uterine cavity | E17 | Intra-amniotic injection | E21 | No | Yes | No |
Feng. 2016(41) | Normal Lewis rat fetus | MSCs | Amniotic fluid and placenta (E21) | Sprague-Dawley rat | Retinoic acid (60 mg/kg) | E10 | 1 × 105 cells/uterine cavity | E17 | Intra-amniotic injection | E21 | Yes | Yes | No |
Shieh. 2018(42) | Normal Lewis rat fetus | MSCs | Amniotic fluid (E21) | Sprague-Dawley rat | Retinoic acid (60 mg/kg) | E10 | 1 × 105 cells/uterine cavity | E17 | Intra-amniotic injection | E22 | Yes | No | No |
Lazow. 2020(43) | Normal Lewis rat fetus | MSCs | Amniotic fluid (E21) | Sprague-Dawley rat | Retinoic acid (60 mg/kg) | E10 | 1 × 105 cells/uterine cavity | E17 | Intra-amniotic injection | E21 | Yes | Yes | No |
Shieh. 2019(40) | Fetal New Zealand rabbit | MSCs | Amniotic fluid | New Zealand rabbit | Surgical creation | E22-23 | 6 × 106 cells/uterine cavity | E22-23; immediately after surgical creation | Intra-amniotic injection | E30-32 | Yes | Yes | No |
Abe. 2019(44) | Human | MSCs | Amniotic fluid (GA 15-17 weeks) | Sprague-Dawley rat | Retinoic acid (60 mg/kg) | E10 | 1 × 105 cells/uterine cavity | E17 | Intra-amniotic injection | E21 | Yes | Yes | Yes |
Kajiwa ra,2017(45) | Human, trisomy 21/TTTS | Skin derived from iPSCs | Amniotic fluid (GA 29 weeks) | Sprague-Dawley rat | Retinoic acid (60 mg/kg) | E10 | 3D skin trans plantation | E20 | Collagen type I scaffold | E22 | Yes | Yes | No |
Fauza. 2008(47) | Mice | NSCs | Cerebellum | Ovine | Surgical creation | GA 97-112 days | 2 × 108 cells/spinal cord | 14-25 days after surgical creation | Direct spinal cord injection | GA 145 days | Yes | No | Yes |
Turner. 2013(48) | Lewis rat fetuses with NTDs | NSCs | Amniotic fluid (E19-E21) | Lewis rat | Retinoic acid (60 mg/kg) | E10 | 1.5 × 104 cells/uterine cavity | E17 | Intra-amniotic injection | E21 | Yes | No | No |
Saadai. 2013(49) | Human | NCSCs | iPSCs | Ovine | Surgical creation | GA 75 days | 2-3 × 107 cells/spinal cord | GA 100 days | Hydrogel on nanofibrous scaffold* with | GA 135 days | Yes | No | No |
Wang. 2015(50) | Human | MSCs | Placenta (11-17 weeks) | Ovine | Surgical creation | GA 77 days | 5 × 105 cells/spinal cord | GA 104 days | 2 mg/ml rat tail collagen | GA 146 days | Yes | No | Yes |
Brown. 2016(51) | Human | MSCs | Placenta (17 and 40 weeks) | Ovine | Surgical creation | GA 75 days | 17 weeks; 5 × 105 cells/spinal cord 40 weeks; 1 × 106 cells/spinal cord | GA 100 days; 25 days after surgical creation | 2 mg/ml rat tail collagen | GA 145 days | Yes | No | Yes |
Kabagambe,2017(52) | Human | MSCs | Placenta (2nd trimester) | Ovine | Surgical creation | GA 78 days | 5 × 105 cells/spinal cord | GA 103 days; 25 days after surgical creation | SIS-ECM | GA 145 days | No | No | Yes |
Chen. 2017(53) | Human | MSCs | Placenta (15 weeks) | Sprague-Dawley rat | Retinoic acid (40 mg/kg) | E10 | 1.6×, 3.1×, 6.3,9.4 × 105 cells/spinal cord | E19 | SIS-ECM | E21 | No | No | Yes |
Vanover,2019(54) | Human | MSCs | Placenta (2nd trimester) | Ovine | Surgical creation | GA 77 days | 5 × 105, 2 × 106 or3 × 106 cells/spinal cord | GA 102 days; 25 days after surgical creation | SIS-ECM | GA 145 days | Yes | No | Yes |
Galganski,2019(55) | Human | MSCs | Placenta (14-21 weeks) | Ovine | Surgical creation | GA 76 days | 3.6 × 106 cells/spinal cord | GA 102 days | SIS-ECM | GA 146 days | No | No | Yes |
Abbreviations: BM, bone marrow; E, embryo; ESCs, embryonic stem cells; GA, gestational age in days using data from the study or calculated from study methods; HH, Hamburger and Hamilton stage;62 iPSCs, induced pluripotent stem cells; MMC, myE10meningocele; MSC, mesenchymal stem cells; NTDs, neural tube defects including exencephaly and/or myE10meningocele; NCSCs, neural crest stem cells; SIS-ECM, small intestinal submucosa-derived extracellular matrix; w, weeks of gestation; TTTS, twin to twin transfusion syndrome.
Volume ratio of NCSCs/hydrogel = 2:1 spread on nanoĥbrous scaffold comprising poly(L-lactide-co) caprolactone, polypropylene glycol and sodium acetate fabricated by electrospinning process.