Table 2 General characteristics of the included studies in this meta-analysis. Transplantation of BMMSCs for the treatment of animal models with Alzheimer’s disease was characterized by source of stem cells, amount of stem cells, animal species, gender, age, body weight, delivery method, etc.
Studies | Sources of transplanted stem cells | Amount of transplanted stem cells | Species of recipient animals | Gender ratio of recipients | Age or body weight | Route of delivery | Position of delivery | Sustainability of transplanted stem cells |
|---|---|---|---|---|---|---|---|---|
Bae, 2013 | Tibias and femurs were dissected from 4- to 6-week-old C57BL/6 mice | 1 × 106 of the cells in a 2uL volume | TASTPM mice (n = 9 for each group) | Female only | 4 months of age. | Transplanted bilaterally into hippocampus | The following coordinates: 2 mm posterior to the bregma, 1.5 mm bilateral to the midline, and 2 mm ventral to the skull surface. | Mice were sacrificed at 2, 3, and 4 months after BMMSC transplantation. |
Garcia, 2014 | 6-week-old C57BL/6-Tg (ACTBEGFP)10sb/J transgenic mice | 1 × 106 of the cells in a 5uL volume | 2xTg-AD male congenic mice (APPswe/PS1dE9, B6.Cg-Tg (APPswe,PSEN1dE9)85Dbo/J) | Male congenic mice (n = 10/group) | 6, 9 and 12 months of age | Lateral ventricle | The coordinates for stereotaxical injection (atlas by Paxinos and Franklin 2004) were used:−0.34 mm posterior to bregma, −0.9 mm lateral to the midline and 2.3 mm ventral to the skull surface | 40 days after transplantation |
Harach, 2017 | Stem cells were obtained from Stemedica Cell Technologies (San Diego, USA). The cells are equivalent to commercially available stemcells from ThermoFisher Scientific “StemPro BM MSC” (part numberA15653). | 5 × 105 cells in 100uL of LRS | APP/PS1 mice | Male:female = 1:1 (n = 5/group) | 1 ~ 12.5-month-old | Single intravenous or weekly intravenous for 10 weeks | Tail vein | 10 weeks |
Kanamaru, 2015 | C57BL/6-Tg (CAG-EGFP)mice(4 weeks old, male) | 5 × 106 cells in 0.25 mL of HBSS | Tg2576 (APP) and DAL | Female only (n = 8 ~ 12/group) | 6-month-old APP mice/9-month-old DAL mice | Peripheral vein | Retroorbital venous plexus | 3 months/9 months |
Lampron, 2013 | Mouse femurs and tibias were dissected, and their bone marrow was flushed with phosphate-buffered saline (PBS) containing 5% fetal bovine serum, recipient mice were treated with a regimen of myeloablative chemotherapy prior to receiving bone marrow cells from GFP1 transgenic mice | 2 × 107 | APP/PS1 and wild-type C57/BL6 mice | Unknown | 7 ~ 8-week-old mice | Peripheral vein | Tail vein of recipient mice | 2.5–10 weeks before they received any other treatment or surgeries. |
Lee, 2010 | 4- to 6-week-old C57BL/6 mice | 1 × 105 cells in 3 μl of the cell suspension | Aβ induced AD (Aβ, n = 20; PBS, n = 10) | Unknown | 4 ~ 6-week-old | Hippocampus bilaterally | The brain coordinates: 1.6 mm posterior to the bregma, 1.7 mm bilateral to the midline, and 1.2 mm ventral to the skull surface. | Mice were sacrificed at 11 days after BM-MSCs transplantation. |
Lee, 2010 | 4 to 6-week-old C57BL/6 mice | 1 × 104 per mouse/3ul | APP/PS1 mice | Male mice | 7 months 1 week of age | Hippocampus bilaterally | The following coordinates: 1.6 mm posterior to the bregma, 1.7 mm bilateral to the midline, and 1.2 mm ventral to the skull surface. | At 9 months of age, mice were killed and evaluated for changes. |
Lee, 2012 | Bone marrow of the mice expressing green fluorescent protein (GFP) | 1 × 104 per mouse/3ul | APP/PS1-GFP Chimeric Mice (n = 10 per group) | Unknown | 7 months 2 week of age | Intracerebral hippocampus | The following coordinates: 1.6 mm posterior to the bregma, 1.7 mm bilateral to the midline, and 1.2 mm ventral to the skull surface | Mice were sacrificed at 3, 7, and 14 days after the last treatment. |
Li, 2011 | UBC-GFP mice with the genetic background of C57BL/ 6 J, UBC-GFP mice (8 to 10 weeks old) | 1 × 107 cells per mouse | APP/PS1 mice. Six weeks after bone marrow transplantation, mice were randomly divided into a saline control group (n = 5) and an SCF + G-CSF-treated group (n = 5). | Unknown | 7-month-old APP/PS1 mice | Peripheral vein | Tail vein | After treatment for 9 months,the mice were sacrificed |
Li, 2012 | The 5th passaged human BMMSCs labeled with PKH26 | 1 × 106 of the cells in a 1000uL volume | SD rats | Male only (10 rats per group) | 3 months of age, ~ 300 g | Peripheral vein | Tail vein | 14 days |
Liu, 2015 | Mouse BMMSCs overexpressed antisense of miRNA-937 | 1 × 106 of the cells in a 5uL volume | APP/PS1 mice | Unknown; n = 10/group | 9 months of age | Bilateral hippocampi | The stereotaxic coordinates were as follows: 2 mm posterior to the bregma, 2 mm bilateral from the midline, and 2 mm ventral to the skull surface. | At 9 month for SR and PM-DAT evaluation |
Magga, 2012 | Monocytic cells-derived from mouse or human bone marrow. | 3 × 105 in 1 ul of HBSS, 2% FBS | APPswe/PS1dE9 (APdE9) mice | Unknown, n = 5 for AD and n = 4 for WT mice | 2-year-old | Intrahippocampal (right hippocampus) | The brain coordinates: 0.25 mm medial/lateral,0.27 mm anterior/posterior,0.25 mm dorsal/ventral from bregma. | After 4 days post-transplantation, the brains were collected |
Matchynski-Franks, 2016 | BMMSCs from C57BJL/6 or GFP-positive mice | 2 × 105 cells/μl in HBSS, 4 μl per mouse | 5xFAD | Male:female = 1:1; LV (n = 8), [2] Hipp (n = 8), [3]LV-Hipp (n = 8), [4] WT Sham (n = 6), [5] AD Sham(n = 6),WT surgery control (n = 6), and AD surgery control (n = 6) | 6 months of age | Central nervous system | Hippocampus and /or ventricle; A burr hole was drilled on each side of the skull, directly over the site of injection at −0.2 anterior/posterior from bregma (A/P) and ± 1.0 medial/lateral from bregma (M/L) into the ventricle, −1.2 A/P and ± 1.0 M/L into the hippocampus, or all four locations. | 10 weeks after transplantation |
Naaldijk, 2017 | C57BL/6 mouse as a source for bone marrow-derived MSC. MSCs at passage 1–2 were used for transplantations | 1 × 106 of the cells in a 150uL volume | APP/PS1 mice | Male animal (day 7 n = 3 and day 28 n = 4), female recipients (day 28, n = 3), control mice n = 11 | 12 ~ 15 months of age | Peripheral vein | Tail vein | 7 or 28 days animals were sacrificed |
Ruzicka, 2016 | Human mesenchymal stem cells (MSCs) | 6 × 104 cells/2 μLof saline | 3xTg-AD mice. The 3xTg-AD mouse strain (LaFerla, Irvine, CA, USA), harboring three transgenes ofPS1 (M146V), tau (P301L) and APP (SWE), was used. Mice (saline-injected 3xTg-AD, n = 14; MSC-injected 3xTg-AD, n = 16; and WT controls without treatment, n = 14) | Unknown | 8 months of age | left lateral ventricle | Coordinates from bregma: anteroposterior = 0 mm, mediolateraly = 1 mm, dorsoventraly = 2 mm | 6 months |
Safar, 2016 | Bone marrow was aspirated from the femora and tibiae of adult male syngeneic Fisher-344 rats. The interphase layer containing bone marrowderived mononuclear cells (BM-MNCs) was collected, and the cells were washed twice with phosphate-buffered saline (PBS) before centrifugation at 400 g for 5 min. | 2 × 106 cells, BM-EPCs | Adult Wistar rats | Male only (12 rats per group) | Weighing 180–220 g | Peripheral vein | Tail vein | One month |
Selem, 2014 | Bone marrow was harvested by flushing the tibiae and femurs of 6-week-old male Sprague–Dawley rats with Dulbecco’s modified Eagle’s medium (DMEM, GIBCO/ BRL, Grand Island, NY, USA) supplemented with 10% fetal bovine serum (GIBCO/BRL). | 3 × 106cells/rat | Adult Sprague–Dawley rats, orally administered with aluminum chloride at 17 mg/kg b. wt. (Krasovskiietal.,1979) daily for75 days for induction of AD disease. | Adult female rats (8rats/group) | Weighing130–150 g | Intravenously | Tail vein in 5 min with a 27G needle | 4 months |
Wu, 2011 | Bone marrow was harvested from Wister rat. | 1 × 105 cells in 5 μl/per side | SD rats | Male rats (15 rats per group) | 3 ~ 4 months | Hippocampus bilaterally | Coordinates: 4.0 mm posterior to the bregma, 2.0 mm bilateral to the midline, and 3.0 mm below the dura mater. | One month |
Yu, 2018 | The femoral bones were harvested from 4 donor male rats. | 3 × 106 cells/rat in a single dose | Sprague-Dawley rat | Female rats (n = 8 per group) | Body weight 130-150 g | Peripheral vein | Tail vein | Unknown |
Zhang, 2012 | Six healthy Sprague-Dawley rats (used for cell culture), aged 2–3 weeks, weighing 80–120 g | 5 × 106 in 10 μl | A randomized, controlled, animal experiment. Adult Sprague-Dawley rats, | Male rats (??rats per group) | Weighing 280–300 g | Lateral ventricular | Stereotaxic Coordinates described by George Paxinos [4]: Neurobiol Aging. 2009;30 [3]:377–387; left ventricle was localized at 1.0 mm posterior to Bregma and 1.5 mm adjacent to the median, and 4.0 mm below the dura mater. | Tests were performed at 16 days and was completed at 20 days. |