Table 3 Characteristics of studies included
From: The efficacy of adipose-derived stem cells in burn injuries: a systematic review
Study | Year | Animal model | Wound conditions | ADSCs origin | ADSCs-Dose | Carrier | Application | Comparison group | Duration | Outcome |
|---|---|---|---|---|---|---|---|---|---|---|
Oryan et al. [17] | 2019 | Animal: Sprague–Dawley rats Quantity: 12 Age: 7–9 weeks Weight: 180–220 g Gender: male | Four circular full thickness burn wounds 10 mm in diameter were created on the back of each rat by an aluminium bar (100 °C) Prior to the treatment, a debridement was performed | Allogeneic Rat ADSCs | 1 × 106 cells | Aloe vera hydrogel | Intradermal injection | • DBM-Aloe vera/ADSCs • DBM-Aloe vera • DBM • Aloe vera | 7, 14 and 28 days | • Accelerated wound closure • reduced Inflammatory cells • IL-1β ↓ • TGF-β1 ↑ • bFGF↑ • Increased neovascularisation • more organised collagen • fibroblasts ↑ • Increased re-epithelialisation |
Zhou et al. [18] | 2019 | Animal: Sprague Dawley rats Quantity: 27 Age: 1 year Weight: No information given Gender: male | A third-degree burn wound (2cm2) was created by putting the head of a temperature-controlled desktop scalding instrument (100 °C) on the back of each rat with a pressure of 1000 g | Autologous Rat ADSCs | 2 × 106 cells | Resuspended in 500 μl PBS | Subcutaneous injection | • ADSCs single injection • ADSCs multiple injection • Control | 3, 12, 21 and 27 days | • Accelerated wound closure • Increased neovascularisation • VEGF ↑ • IL-1ra ↑ |
Oryan et al. [19] | 2019 | Animal: Sprague–Dawley rats Quantity: 12 Age: 7–9 weeks Weight: 180–220 g Gender: male | Four circular full thickness burn wounds 10 mm in diameter were created on the back of each rat by an aluminium bar (100 °C) Necrosis was removed 48 h post-burn | Allogeneic Rat ADSCs | 1 × 106 cells | Tegaderm-honey | Intradermal injection | • Tegaderm-honey-ADSCs • Tegaderm + honey • Tegaderm • Honey | 7, 14, and 28 days | • Accelerated wound closure • wound closure rate ↑ • Reduced Inflammatory cells • bFGF ↑ • TGF-β1 ↑ • IL-1β ↓ • blood vessels ↑ • Increased granulation tissue formation • Increased re-epithelialisation • More organised collagen • Hair follicle ↑ |
Kaita et al. [20] | 2019 | Animal: BALB/c nude mice Quantity: 18 Age: 6–8 weeks Weight: Information is not given Gender: male | Full-thickness burn wounds were created by placing a pre-heated (150 °C) aluminum column (6 mm in diameter) on the dorsum for 5 s | Human ADSCs | 5 × 104 cells | Terudermis™ Artificial dermis | Direct application of ADSCs loaded artificial dermis | • Fresh ADSCs • Frozen ADSCs • control | • 6 and 12 days | • Reduced wound surface • Increased skin thickness • Increased neovascularisation • HGF ↑ • Increased collagen synthesis |
Banerjee [21] | 2019 | Animal: Harlan rats Quantity: 16 Age: 8–10 weeks Weight: Information is not given Gender: male | A circular deep partial thickness burn was created using a brass soldering device (17 mm diameter) heated to 87 °C. The device was applied to the dorsal area of rats for 10 s with a constant force of 500 g using a weighted soldering tip. After 12 h, the wounds of groups 2–4 were infected with P. aeruginosa | Rat ADSCs “no mention of whether allogeneic or autologous source” | 5 × 104 cells | PEGylated fibrin hydrogel containing of silver sulfadiazine (SSD) loaded chitosan microsphere | Application within Hydrogel as wound dressing | • Uninfected control • Infected saline • Infected PEGylated fibrin hydrogel containing of silver sulfadiazine (SSD) loaded chitosan microsphere • Infected PEGylated fibrin hydrogel containing of silver sulfadiazine (SSD) loaded chitosan microsphere with ADSCs | 1, 4, 7, 14, 21 and 28 days | • Increased neovascularisation • Increased collagen deposition • More organized & thicker granulation tissue • Increased re-epithelialisation |
Loder et al. [22] | 2014 | Animal: C57BL/6 mice Quantity: 20 Age: 6–8 weeks Weight: 20-25 g* Gender: male | All animals underwent a 30% surface area partial- thickness scald injury by exposure to 60 °C water for 17 s | Allogeneic Mouse ADSCs | 1 × 106 cells | Suspended in 500 μl PBS | Subcutaneous injection | • Processed adipose tissue • ADSCs • Adipose tissue/ADSCs • sham | 5 and 14 days | • Decreased wound depth on day 5 • Decrease in cell apoptosis • Increased neovascularisation |
Motamed et al. [23] | 2017 | Animal: Sprague–Dawley rats Quantity: 32 Age: Information is not given Weight: 280–320 g Gender: male | A full thickness burn injury was induced on each rat by laying a bar with four columns (10 × 20 mm), which was kept in boiling water for 5 min on the dorsum for 30 s | Human ADSCs | 5 × 105 cells | Human amniotic membrane | Direct application of ADSCs loaded human amniotic membrane | • Vaseline gauze (control) • human amniotic membrane (HAM) • fetal fibroblasts seeded on HAM • ADSCs seeded on HAM | 0, 7, 14, 20, 28, 40, 50 and 60 days | • Accelerated re-epithelialisation • reduced inflammatory cell • less fibrosis • decreased healing time |
Gholipourmalekabadi et al. [24] | 2018 | Animal: BALB/c male mice Quantity: 75 Age: 4–6 weeks* Weight: 16–19 g* Gender: male | Two full-thickness burns (1 cm in diameter) were produced on the back of each mouse by placing a heated metal sheet (100 °C) for 10 s The necrotic tissue resulting was meticulously debrided before fat grafting | Allogeneic Mouse ADSCs | 1 × 104 cells | Bi-layered 3D artificial skin made from decellularized human amniotic membrane | Direct application of ADSCs loaded artificial skin | • Control • human amniotic membrane (AM) • ADSCs/AM • AM/ESF • ADSCs/AM/ESF | 7, 14 and 28 days | • Accelerated wound closure • Support early inflammatory response • Increased neovascularisation • Increased re-epithelialisation • Reduced scar elevation index (SEI) • Hair follicle ↑ • TGF-β1 ↑ • MIP2 ↓ • TNF-α1 ↓ • MMP-1 ↑ • MMP-2 ↑ • IL-1β ↑ • bFGF ↑ |
Bliley et al. [25] | 2016 | Animal: athymic nude mice Quantity: 24 Age: 7–9 weeks Weight: 25-30 g* Gender: female | A full-thickness burn (1 cm diameter) injury was created on the dorsum of each mouse by a brass stamps, which were wrapped in aluminium foil and heated overnight in a Fisher convection oven at 70 °C | Human ADSCs | 6.8 × 106 cells | Resuspended in o.5 ml PBS | Subeschar injection | • Control (PBS) • ADSCs/PBS | 4, 7, 14, and 21 days | • Increased collagen formation • Increased neovascularisation • Collagen I ↑ • Collagen III ↑ • Higher ratio of III to I collagen |
Alemzadeh et al. [26] | 2019 | Animal: Sprague–Dawley male rats Quantity: 12 Age: 8 weeks Weight: 200–250 g Gender: male | Three circular full-thickness burn injuries (10 mm in diameter) were created on the back of each rat by an aluminum bar boiled in 100 °C water for 30 s Necrosis was removed 48 h post-burn | Allogeneic Rat ADSCs | 1 × 106 cells | Hyaluronic acid hydrogel | Intradermal injection and topical application | • ADM • Hyaluronic acid + ADM • Hyaluronic acid/ADSCs + ADM | 0, 7, 14, and 28 days | • Accelerated wound closure • IL-1β ↓ • TGF-β1 ↑ • bFGF ↑ • Fibroblasts ↑ • Increased neovascularisation • Increased re-epithelialisation • Accelerated remodelling |
Dong et al. [27] | 2020 | Animal: FVB/NJ mice Quantity: 15 Age: 10–12 weeks Weight: Information is not given Gender: female | Two deep second-degree burns were made on the dorsum of each mouse by using an aluminium cylinder (10 mm diameter) heated in a 100 °C water bath for 10 min Two days after burning, all necrotic tissue was debrided to create a fresh full-thickness wound | Human ADSCs & Allogeneic Mouse ADSCs | 3 × 105 cells | Hydrogel | Application within Hydrogel as wound dressing | • Hydrogel + ADSCs • Hydrogel • Control (no treatment) | 3, 9, 11, 14 and 21 days | • Accelerated wound closure • Increased neovascularisation • Higher ratio of III to I collagen • Myofibroblasts↓ |
Cabello-Arista et al. [28] | 2022 | Animal: athymic nude mice Quantity: 25 Age: 3 months Weight: 24–26 g* Gender: male | To create a third degree burn injury a 105 °C heated cooper device (2 cm2) was placed on the back of each mouse for 5 s and quickly removed Burned area was debrided with a scalpel to remove necrotic tissue | Human ADSCs | 2 × 104 cells | Radiosterilized human amnion (RHA) or radioster- ilized pig skin (RPS) | Direct Application with ADSCs loaded RHA or RPS | • RHA + ADSCs • RPS + ADSCs • RHA • RPS • Control (gauze with petroleum jelly) | 7 and 14 days | • Improved collagen deposition • Collagen I ↑ |
Feng et al. [29] | 2019 | Animal: Sprague Dawley rats Quantity: 12 Age: Information is not given Weight: 250–300 g Gender: Information is not given | A copper plate (1 cm2), heated to 90ºC was applied on the dorsum of each rat for 30 s to create three deep partial thickness burns on two strips of skin islands respectively. After treatments the skin islands were embedded into the subcutaneous pockets | Rat ADSCs “no mention of whether allogeneic or autologous source” | 5 × 105 cells | Resuspended in 0.2 mL PBS | Intradermal injections | • ADSCs • Control | 7, 14, 21 and 29 days | • Improved hair growth • Number of live hair follicle↑ • Increased neovascularisation |
Barrera et al. [30] | 2021 | Animal: eC57BL/6 J mice Quantity: 24 Age: 8–12 weeks Weight: Information is not given Gender: Information is not given | Two partial thickness burns were created on each mouse dorsum with aluminium cylinders (10 mm in diameter) heated in a 100 °C water bath for 5 min and applied on the animals for 15 s Burns were debrided 5 days post injury using a blunt stainless steel rod | Mouse ADSCs “no mention of whether allogeneic or autologous source” | 2.5 × 105 cells | Hydrogel Or albumin-containing media | Application with Hydrogel as wound dressing or Injection (The location or depth of the injection was not disclosed.) | Experiment A: • ADSCs hydrogel • ASC injection • Hydrogel • Control (no treatment) Experiment B • CD26 + CD55 + ADSCs • FACS-sorted ADSCs, • unsorted ADSCs • SVF • Control (no treatment) | Experiment A: 10 and 25 days Experiment B: 29 days | • Accelerated wound closure • Increased re-epithelialisation • Increased neovascularisation • MCP-1↑ • VEGF↑ • TIMP1↓ • TNF-α↓ • Less scarring |
Azam et al. [31] | 2021 | Animal: Wistar rats Quantity: 22 Age: 3–4 months Weight: 200–250 g Gender: male | A sterile filter paper disc (20 mm in diameter) was soaked in 12.06 N HCl (Merck, USA) for 1 min and applied at the dorsal side of the neck for 10 min to inflict the acid burn injury 24 h after injury, the necrotic tissue was carefully removed and deep partial thickness wounds were revealed | Allogeneic rat ADSCs | 2 × 106 cells | Dulbecco's Modified Eagle Medium (DMEM)-Low Glucose with and without 5 μM curcumin | Intradermal injection | • ADSCs • Curcumin –preconditioned ADSCs • Control (saline) | 4, 8, 12, 16, 20 and 24 days | • Accelerated wound closure • Reduced inflammation cells • Increased re-epithelialisation • Increased granulation tissue formation • Increased collagen deposition • IL-1β↓ • IL-6↓ • TNF -α↓ • VEGF↑ • HGF↑ • HIF-1 –α↑ • TGF- β1↑ • FGF-2↑ • Col1α1↑ |
Foubert et al. [32] | 2015 | Animal: Gottingen minipigs Quantity: 8 Age: 5–6 months Weight: 12–16 kg Gender: female | A custom-made brass block (3.5 cm in diameter), pre-heated to 180–200 °C and weighing 350 g, was pressed onto the dorsum of the animal with a pressure of 0.4 kg/cm2 for 1 min to create six full-thickness burns per side were induced on the dorsum of each animal | Autologous Pig ADSCs | 6,25 × 106 cells | Collagen-based matrix (CBM) (i.e. Integra ®) | Direct application with the collagen-based matrix layer | • ADSCs • Control (CBM alone) | 7, 14, 21 and 28 days | • Increased neovascularisation • Increased collagen deposition • More organized & thicker granulation tissue |
Roshangar et al. [33] | 2021 | Animal: Rats Quantity: 36 Age: Information is not given Weight: Information is not given Gender: male | A full-thickness cutaneous wound of 2 × 2 cm was induced on the back of each rat through scaldingt After 24 h, the necrotic tissue was removed The temperature at which the burns were inflicted was not specified in the document | Rat ADSCs “no mention of whether allogeneic or autologous source” | 1 × 105 cells | 3D-biorinted gel scaffold | Direct application with the scaffold | • 3D bioprinter derived‐gel scaffold + ADSC • 3D bioprinter derived‐gel scaffold • Control (no treatment) | 5, 14 and 21 days | • Accelerated wound closure • Reduced inflammatory cells • Increased neovascularisation • Organized collagen deposition • Increased re-epithelialisation |
Wu et al. [34] | 2021 | Animal: Balb/c mice Quantity: 32 Age: 8 weeks Weight: Information is not given Gender: male | After removal of the dorsal hairs, heated steel rods with a diameter of 14 mm and a temperature of 100 °C were applied for one minute to cause full thickness burns Two days post-injury, the necrotic skin was excised, and a silicone ring was stitched around the wound area for protection and containment | Allogeneic Mouse ADSCs | 2 × 106 cells | 3D-biorinted gel scaffolds | Direct application with the scaffold | • 3D-ADSCs • 3D-NO • 3D-ADSCs/No • Control (gauze) | 0, 7 and 14 days | • Accelerated wound closure • Increased neovascularisation • Increased collagen deposition • Increased re-epithelialisation |
Franck et al. [35] | 2019 | Animal: Wistar rats Quantity: 23 Age: 3 months Weight: 250–280 g Gender: male | Burns were induced by placing a square ceramic pattern (484 mm2) on the abdomen, heated to 100 °C. The ceramic was applied with its own weight equivalent to 54 g for thirty seconds, resulting in a full-thickness skin injury | Allogeneic Rat ADSCs | 3.2 × 106 cells | DMEM | Intradermal injection | • ADSCs • Control (no treatment) | 4,7 and 14 days | • Accelerated wound closure • Reduced inflammatory cells • Increased collagen deposition |
Karimi et al. [36] | 2014 | Animal: Balb/c mice Quantity: 30 Age: Information is not given Weight: 40 g Gender: male | A heated metal probe, with a surface area of 1.5 cm2 and a temperature of 96 °C, was applied to the backs of the mice for 8 s to produce a standard full-thickness burn injury | Allogeneic Mouse ADSCs | 1 × 106 cells | Physiologic serum | Intradermal injection | • ADSCs • Adipocytes • Control (no treatment) | 7, 14 and 21 days | • Accelerated wound closure • Reduce inflammatory cells • Increase re-epithelisation • Fibroblasts ↑ |
Ng et al. [37] | 2021 | Animal: C57BL/6NTac mice Quantity: 42 Age: 6–8 weeks Weight: Information is not given Gender: female | A stainless-steel bar measuring 6 mm × 5 mm and weighing 96.2 g was heated in a water bath at 100 °C for 15 min. To induce a full-thickness burn injury, the hot surface of the bar, was placed on the shaven posterior-dorsum of each mouse for a duration of 30 s The eschar was removed 48 h post-burn, directly before treatment | Human ADSCs | 6 × 104 cells | Hydrogel | Application with hydrogel as wound dressing | • Hydrogel/ADSCs • Hydrogel soaked in ADSCs-conditioned media • Hydrogel • Control (no treatment) | 0, 7, 14 and 21 days | • Accelerated wound closure • Reduce inflammatory cells • Hair follicle & sebaceous glands ↑ |