Table 3.
Characteristics of studies observing MSC effects on scar formation from wounds
| Author | Method of delivery | Model | Scar characteristics | Subject (n =) | Control (n =) | Follow-up duration | Assessment | Outcome |
|---|---|---|---|---|---|---|---|---|
| Hu et al. (2019) |
1 × 106 cells/ml (200 μl of 2 × 105 MSC) in conditioned medium (CM), bone marrow concentrate (BMC) CM, or BMC-treated MSC CM or control (Dulbecco’s modified Eagle medium (DMEM)) injected subcutaneously into each wound on day 14, 21, 28 |
Rabbit | Hypertrophic scar (HS)-Full-thickness, 1 cm diameter circular wound, ear | MSC CM (n = 4) BMC CM (n = 4) BMC-treated MSC CM (n = 4) | DMEM into contralateral ear wound (n = 12) | Day 35 | Macroscopic appearance, histology and immunohistochemistry, collagen gel contraction assay | Improved wound appearance and reduced HS formation in BMC-treated MSC CM compared with other groups. BMC-treated MSC CM also reduced fibroblasts and HS contracture |
| Foubert et al. (2017) | 0.25 × 106 cells sprayed topically onto each square centimetre of wound or lactated Ringer's (LR) | Pig | HS-Full-thickness 2-mm depth, 58-cm2 wound, flanks | MSC (n = 12) | LR sprayed topically onto contralateral flank wound (n = 12) | Day 60 or 180 | Macroscopic appearance, histology, biomechanical assessment of elasticity, collagen deposition assay, digital planimetry | Reduced scarring, improved scar pigmentation and epidermal remodelling. Reduced collagen deposition and enhanced elastic fibre length compared with control groups. Reduced scar tissue hardness and vascularisation. Higher levels of IL-6 and TNF-alpha compared with control. No difference in wound contracture |
| Yates et al. (2017) | 2 × 107 cells/ml (50 μl of 1 × 106 MSCs), MSC-tenacin C (TNC), MSC-fibroblast co-culture mixture or MSC-TNC fibroblast co-culture mixture subcutaneously injected into each wound | Murine | HS-Full-thickness, 8 mm punch wounds, dorsum | MSC-TNC on WT mice (n = 3) MSC-TNC on Chemokine receptor 3 (CXCR3) -/- mice (n = 3) MSC-TNC fibroblast on WT mice (n = 3) MSC-TNC fibroblast on CXCR3-/- mice (n = 3) | HA (n = 3) MSC-HA (n = 3) on both wild type and CXCR3-/- mice | Day 30 | Macroscopic appearance, histology, immunohistochemistry, immune cell infiltration analysis and fluorescent apoptosis assay (caspase-3 staining) | Reduced scarring in MSC-TNC fibroblast co-culture mixture group compared with other groups. Reduced fibroblast apoptosis when co-cultured with MSCs |
| Yates et al. (2017) | Wounds filled with tenascin C in a collagen/GAG-based (TPolymer) or MSC-TPolymer or left untreated and covered with Tegaderm | Murine | HS-Full-thickness, 6-mm punch wound, dorsum | MSC-TPolymer on wild type (WT) mice (n = 3) MSC-polymer on CXCR3-/- mice (n = 3) TPolymer on WT mice (n = 3) TPolymer on CXCR3-/- mice (n = 3) | No treatment on contralateral dorsal wound on both wild type and CXCR3-/- mice (n = 12) | Day 3, 7, 14, 21, 60 or 90 | Macroscopic appearance, histology, immunohistochemistry | Reduced scarring by improved collagen alignment in MSC-TPolymer group compared with TPolymer group only. Improved wound repair and dermal maturation in MSC-TPolymer group. TPolymer enhances MSC survival |
| Li et al. (2016) | 1000 μl of varying concentrations of MSC CM derived from passage 3–5 MSCs at 80–90% confluence subcutaneously injected into each wound | Murine | HS-Full-thickness, 1-cm2 area wound, dorsum | 10% MSC CM (n = 6) 20% MSC CM (n = 6) 40% MSC CM (n = 6) 80% MSC CM (n = 6) | DMEM (n = 6) | Day 14 | Macroscopic appearance, histology, immunohistochemistry | Reduced scar formation, reduced skin fibrosis, faster wound healing in MSC CM group. Decreased collagen deposition, reduced collagen I and III expression in a concentration-dependent manner |
| Zhang et al. (2015) | 200ul of MSC or MSC CM or DMEM injected into centre of each wound | Rabbit | HS-Full-thickness, 1-cm2 area wound, ear | MSC (n = 4) MSC CM (n = 4) | Untreated (n = 4) DMEM on contralateral ear wound of each group (n = 12) | Day 35 | Macroscopic appearance, histology, immunohistochemistry, ultrasonography to assess scar thickness | Reduced scar hypertrophy in both MSC and MSC CM group. MSC group more effective than MSC CM group. Reduced scar tissue height |
| Liu et al. (2014) | 6.25 × 106 cells/ml (80 μl of 5 × 105 MSCs) or PBS injected intradermally circumferentially around each wound | Rabbit | HS-Full-thickness, 7-mm punch wound, ear | Human MSC (n = 6) rabbit MSC (n = 6) human MSC-small interfering RNA (n = 6) human MSC-H2O2 (apoptosis model) (n = 6) human MSC-with capsase-3 inhibitor (anti-apoptotic model) (n = 6) | PBS (n = 6) | Day 14 or 28 | Macroscopic appearance, histology, immunofluorescence, digital planimetry, TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labelling) staining for detecting apoptosis | Attenuated HS formation and reduced HS height in human MSC group. MSC groups showed significant MSC apoptosis shortly after transplantation. Therapeutic effect was attenuated in the anti-apoptotic model |
| Liu et al. (2014) | 1000 μl of MSC (1 × 105 cells) or PBS injected intra-arterially via ear artery | Rabbit | HS-Full-thickness, 9-mm round wound, ear | MSC transduced with p53 shRNA (n = 4) MSC transduced with control short hairpin RNA (shRNA) (n = 4) | PBS (n = 4) | Day 21, 28 or 35 | Macroscopic appearance, histology, immunohistochemistry | Prevented HS formation in a p53 mediated manner. Knockdown of p53 in MSC increased HS fibroblast proliferation |