TABLE 3.
Studies regarding mesenchymal stromal cell-conditioned medium for treating other types of wounds in animal models.
| MSC source | Method of tissue extraction | MSC characterization | Preparation of MSC-CM | Model | Groups of treatments and via of administration | Follow-up (days) | Assessment | Main outcomes | Other outcomes | |
| Zhou et al., 2019 | Human umbilical cords | Umbilical cord section from full-term healthy fetuses that were born via cesarean section | Flow cytometry (CD29+, CD44+, CD73+, CD90+, CD105+, CD34−, CD45, CD31−, CD271−) | MSCs of passages 3–8 at 70–80% confluence were used. CM was collected. The thermosensitive MSC-CM/hydrogel was prepared by mixing the precooled MSC-CM, chitosan/β-GP, and collagen solutions at a ratio of 1:2:1 on ice | Murine. Third-degree burned mice, 15 mm | Wound was covered and changed twice daily - Unconditioned medium (UM) - MSC-CM group - UM/hydrogel - MSC-CM/hydrogel (n = 18/group) |
28 | Macroscopic appearance (photography), histology (HE), IHC | Application of the MSC-CM/hydrogel shortened healing time. The average healing time in MSC-CM/hydrogel group was approximately 5 days shorter than in UM group and shorter than MSC-CM and UM/hydrogel groups | MSC-CM/hydrogel limited the area of inflammation; enhanced re-epithelialization; promoted the formation of high-quality, well-vascularized granulation tissue; and attenuated the formation of fibrotic and hypertrophic scar tissue |
| Sun et al., 2019 | Wharton’s jelly from human umbilical cords | Section from umbilical cords | − | MSCs of passage 3 at 60% confluence were used. CM was collected | Murine. Radiation-induced skin injury rat model, 20 mm × 20 mm | 200 ml of hydrogel was pipetted onto the radiation wound every 2 days - Non-treated - EGF - MSC-CM (n = 12/group) |
56 | Macroscopic appearance (photography), histology (HE), IHC | MSC-CM significantly accelerated wound closure and enhanced the wound healing quality. The great difference was observed at day 42, with a relative wound size of the MSC-CM group 2.63-fold smaller than the EGF group and 3.38-fold smaller than the non-treated group (0.8 ± 0.29, 2.1 ± 0.37, 2.7 ± 0.34 mm2, respectively) | α-SMA, Ki-67 expression, and the number of vessels/HPF were increased in MSC-CM group |
| Li J. Y. et al., 2019 | Human fetal placenta | Placenta section | Flow cytometry adipogenic and qRT-PCR (CD29+, CD73+, CD105+, CD90+, CD34−, CD45−, CD133−). Adipogenic and osteogenic differentiation | MSCs of passages 3–7 at 80% confluence were used. CM was collected | Murine. Second-degree burn injury model. Back skin of mice was injured with 80°C water for 100 s to create a 10-mm diameter wound | 200 μl of the treatments was subcutaneously injected near the wound at four sites - PBS containing 2 × 106 MSCs - MSC-CM - PBS - DMEM (n = 5/group) |
21 | Macroscopic appearance (photography), histology (HE), IF | MSCs and MSC-CMs promoted wound healing compared with PBS and DMEM | High levels of new blood vessels and tubular structures were observed in the MSC and MSC-CM groups |
| Kouhkheil et al., 2019 | Human bone marrow | Aspiration | Flow cytometry | MSCs of passage 4 at 80% confluence were used. CM was collected | Murine. MRSA rats infected. Full-thickness excisional wound, 15 mm, on the back | PBM was administered once daily, 6 days per week. 50 μl of the 10-fold CM was administered from day 0 until day 3 - Control - PBM - MSC-CM - PBM+MSC-CM (n = 18/group) |
15 | Clinical observation, microbiological, tensiometric, and stereological analyses | There was a significant decrease in colony-forming units in PBM+MSC-CM and PBM groups compared with controls | PBM+MSC-CM, PBM, and MSC-CM groups significantly increased wound strength compared with the control group. The PBM+MSC-CM and PBM groups had more stable MCs, less significant degranulated and disintegrated MCs, and less significant total number of MCs compared with the control group |
| Fridoni et al., 2019 | Human bone marrow | Aspiration | Flow cytometry (CD105+, CD90+, CD73+, CD34−, CD45−) | MSCs of passage 4 were used. CM was collected | Murine. MRSA diabetic rats infected. Full−thickness wound, 15-mm diameter round, on the back | PBM was administered once daily, 6 days per week. 500 μl of the 10-fold CM was injected intraperitoneally daily from day 0 until day 3 - Control group - PBM - MSC-CM - PBM+MSC-CM (n = 18/group) |
15 | Histology (HE), IHC | PBM+MSC-CM hastened wound healing process | PBM+MSC-CM, MSC-CM, and PBM groups showed a decrease in the number of neutrophils and macrophages and an increase in the number of fibroblasts and angiogenesis compared with those of the control group |
| Aryan et al., 2019 | Human bone marrow | − | Flow cytometry (CD73+, CD90+, CD105+, CD45−) | MSCs of passages 3–4 at 80–90% confluence were used. CM was collected | Murine. Second-degree burns (induced from boiling water), 30 mm × 30 mm | - Not treated rats (control) - 0.5 ml of DMEM injected intraperitoneally every other day - 1% topical silver sulfadiazine cream daily - 0.5 ml of MSC-CM injected intraperitoneally every other day (n = 5/group) |
28 | Macroscopic appearance (photography), histology (HE, MT), IHC | Wound closure area was significantly increased in the MSC-CM and sulfadiazine groups | There was a reduction in the volume of the epidermis and dermis in the burn wound of the control, DMEM, and sulfadiazine groups compared with the MSC-CM group |
CM, conditioned medium; DMEM, Dulbecco’s modified Eagle medium; ECM, extracellular matrix; EGF, epidermal growth factor; HE, hematoxylin and eosin; IHC, immunohistochemistry; IF, immunofluorescence; MRSA, methicillin-resistant Staphylococcus aureus; MSCs, mesenchymal stromal cells; MT, Masson’s trichrome; PBM, photobiomodulation; PBS, phosphate-buffered saline; qRT-PCR, real-time quantitative polymerase chain reaction.