TABLE 6.
Studies regarding mesenchymal stromal cell-conditioned medium for improving flaps reperfusion in animal models.
| MSC source | Method of tissue extraction | MSC characterization | MSC treatment | Model | Groups of treatments and via of administration | Follow-up (days) | Assessment | Main outcome | |
| Pu et al., 2019 | Human abdominal adipose tissue | Liposuction | Flow cytometry and IHC (CD34, CD45, CD73, CD90, CD105). Adipogenic, osteogenic, chondrogenic differentiation | MSCs of passages 3–8 at 70–80% confluence were used. CM was then collected | Murine. Ischemia/reperfusion flap model by clamping the flap (ischemia) and then releasing it (reperfusion) | Treatment was applied to the subcutaneous layer between the flap and its bed and at the proximal, middle, and distal parts of the skin flap - Saline injections - MSC-CM (n = 6/group) |
5 | Macroscopic appearance (photography), histology (HE, MT), IHC, qRT-PCR | MSC-CM treatment attenuated the necrotic area and reversed the detrimental proliferation effect induced by I/R compared with saline |
| Cooper et al., 2018 | Human adipose tissue | Elective surgery | − | MSCs of at 70–90% confluence were used. CM was then collected. EVs were isolated by centrifugation | Murine. Full-thickness excisional wounds were created in the center of a 105 mm × 35 mm flap (ischemic wounds) | 20 μl topically applied daily - MSC-CM - Control media (n = 6/group) |
21 | Macroscopic appearance (photography) | MSC-CM accelerated closure of ischemic wounds. In MSC-CM-treated group, the wound area reduction was 65% compared with only 15% wound closure for the control |
| Lee S. M. et al., 2014 | Human subcutaneous adipose tissue | − | Flow cytometry (CD29+, CD44+, CD73+, CD90+, CD105+, CD34−, CD45−, CD14−) | MSCs of passage 3 at 80% confluence were used | Murine. Full-thickness skin graft, 30 mm × 30 mm, back | Intravenously injected - PBS - MSCs - MSC-CM (n = 12/group) |
30 | Macroscopic appearance (photography), histology (HE), IHC | MSCs and MSC-CM increased skin allograft survival compared with control (23.9 ± 2.0, 19.6 ± 2.4, and 9.3 ± 1.4 days, respectively), without differences between these both groups |
| Mirabella et al., 2012 | Human amniotic fluid | Amniocentesis | − | MSCs of passage 6 at 80% confluence. Lyophilized gelatine film membranes were prepared by using MSC-CM or saline as control | Murine. Ischemia/reperfusion epigastric flap model. Flap 70 mm × 70 mm with vasculature ligated and then opened | A membrane with MSC-CM or saline was positioned under the elevated skin flap (n = 5/group) | 7 | Macroscopic appearance (photography), histology | Perfusion was increased in flaps treated with MSC-CM compared with controls. Necrosis was decreased in the MSC-CM group |
CM, conditioned medium; EVs, extracellular vesicles; HE, hematoxylin and eosin; IHC, immunohistochemistry; I/R, ischemia/reperfusion; IF, immunofluorescence; MSCs, mesenchymal stromal cells; MT, Masson’s trichrome; PBS, phosphate-buffered saline; qRT-PCR, real-time quantitative polymerase chain reaction.