TABLE 4.
Application of perinatal tissues alone or compared to/combined with perinatal cells or cells of non-perinatal origin in in vivo animal models of skin wound healing. Stated time points in the “Outcome” column mean days (d) or weeks (w) after treatment.
| Perinatal tissues | |||||
|---|---|---|---|---|---|
| PnD | Carrier of the topical PnD application | Wound type, animal | Outcome | References | |
| a) hAM | wa 0.2 cm2 | Topical | Full-thickness, mouse Splint model | hAM-silk fibroin scaffolds achieved better epidermal and dermal regeneration than hAM-treated and untreated wounds (d30) | Arasteh et al. (2020) |
| b) hAM + silk fibroin | |||||
| a) hAM | wa 1.77 cm2 | Topical | Full-thickness, diabetic rat, non-diabetic control rat | hAM-S seemed to have better effects on the healing of diabetic wounds than hAM (d7, d14, d21) | Nasiry et al. (2020) |
| b) hAM-S | Splint model | ||||
| hAM | wa 1.69 cm2 | Topical | Full-thickness, rat | hAM promoted wound closure (d3, d5, d7), and enhanced VEGF and α- SMA expression (d7). Reduced TGF-β1 expression at an early stage (d3) alleviated wound inflammation, promoted tissue regeneration and relieved scar formation compared to PBS treated wounds | Song et al. (2017) |
| Dehydrated hAM/chorion (EpiFix®) | Not applicable | Subcutaneous implantation | Subcutaneous pocket model, mouse | hAM/chorion implants recruited more mesenchymal progenitor cells to the site of implantation compared to normal skin and the sham implant site (d7) | Koob et al. (2013) |
| Dehydrated hAM/chorion (EpiFix®) | Not applicable | Subcutaneous implantation | Subcutaneous pocket model, mouse | hAM/chorion implants displayed a steady increase in microvessels approaching that of healthy and healing skin (d28) | Koob et al. (2014) |
| Perinatal tissues compared to/or combined with perinatal cells | |||||
| PnD | Dosage | Application | Wound type, animal | Outcome | References |
| a) hUC-MSC | 1 × 10^6 cells/cm2 wa 1 cm2 | a) Subcutaneous injection | Full-thickness, mouse | Combination of hUC-MSC and hAM achieved better wound healing (reduced scar formation with hair growth and improved biomechanical properties of regenerated skin) than hUC-MSC alone (d14) and untreated wounds | Sabapathy et al. (2014) |
| b) hUC-MSC+ hAM | b) Topical | ||||
| c) hAM | |||||
| a) hUC-MSC | 0.7 × 10^6 cells/cm2 wa 1.54 cm2 | Subcutaneous injection or topical (b-c) Topical | Burn 3rd degree, rat | hUC-MSC/hAM combination induced better wound healing (re-epithelialization, formation of granulation tissue, and hemorrhage) than hAM and hUC-MSC alone (d14) | Hashemi et al. (2020) |
| b) hAM | |||||
| c) hUC-MSC+hAM | |||||
| Perinatal tissues combined with cells of non-perinatal origin | |||||
| PnD | Carrier of the topical PnD application | Wound type, animal | Outcome | References | |
| a) hAM | wa 11–18 cm2 0.5 × 10^6 cells/cm2 | Topical | Burn 3rd degree, rat | hAM seeded with fibroblasts or with ASC similarly showed better wound healing than hAM-only and control (Vaseline gauze) (d7, d14, d20, d28, d40) | Motamed et al. (2017) |
| b) hAM+hFib | |||||
| c) hAM+hASC | |||||
| a) hAM | wa 0.79 cm2 10,000 cells/cm2 | a) Topical (b-c) Topical silk fibroin | Burn 3rd degree, mouse | Silk fibroin accelerated wound healing compared to hAM only. hAM/silk fibroin+hASC achieved better effects than hAM/silk fibroin without ASC (d7, d14, d28) and reduced post burn scars | Gholipourmalekabadi et al. (2018) |
| b) hAM/silk fibroin | |||||
| c) hAM/silk fibroin+hASC | |||||
| hAM (loaded or injected with autologous or allologous rabbit BM-MSC | wa 5.06 cm2 | Topical | Full-thickness, rabbit | hAM grafts loaded with autologous and allologous BM-MSC similarly accelerated wound closure compared to hAM grafts with injected BM-MSC (d7, d12, d15) | Kim et al. (2009) |
| 88,888 cells/cm2 on hAM | |||||
| 3.02 × 10^6 cells/cm2 i.d | |||||
| a) hAM | wa 2 cm2 number of cells per cm2 Not specified | Topical | Radiation followed by full-thickness, rat | hAM+BM-MSC and hAM+ freeze-dried BM-MSC similarly accelerated wound closure compared to hAM only. Inflammation and exudations were absent when hAM was used in contrast to non-treated wounds (Observation period 90 days) | Kakabadze et al. (2019) |
| b) hAM+BM-MSC | |||||
| c) hAM+ freeze-dried rat BM-MSC | |||||
| a) Dehydrated hAM (Amniofix ®) | wa 4 cm2 0.1 × 10^6 cells/cm2 | Topical | Full-thickness, rat | All treatments resulted in similar wound closure (d7-d21). TGF-β3 expressing cells decreased the scar formation (d85) | Samadikuchaksaraei et al. (2016) |
| b) Amniofix ® +BM-MSC | |||||
| c) Amniofix ® +TGFβ3 expressing BM-MSC | |||||
| a) hAM | wa 2.25 cm2 | Topical | Full-thickness, rat | Men-MSC+hAM improved wound closure, angiogenesis and re-epithelization compared to hAM-only (d14) | Farzamfar et al. (2018) |
| b) hAM+ Men-MSC | 30,000 cells/cm2 | ||||
Abbreviations: α-SMA, alpha-smooth muscle actin; BM-MSC, bone-marrow mesenchymal stromal cells; hAM, human amniotic membrane; hAM-S, bioengineered 3D hAM-scaffold; hASC, human adipose mesenchymal stromal cells; hFib, human fibroblasts; hUC-MSC, human umbilical cord mesenchymal stromal cells; Men-MSC, menstrual blood mesenchymal stromal cells; TGF-β1, transforming growth factor beta-1; VEGF, vascular endothelial cell growth factor; wa, wound area covered by tissue membranes.