Table 2.
Main animal models and results in wound healing.
| Animal model | Wound healing | Biological effects | References |
|---|---|---|---|
| Diabetic wounds | |||
| Full-thickness dermal wound in diabetic (db/db) mice | Multicellular aggregates of human ASCs > ASCs in suspension: rate of wound healing | Multicellular aggregates of human ASC > ASC in suspension: production of extracellular matrix proteins (tenascin C, collagen VI α3, and fibronectin) and secretion of soluble factors (HGF, MMP-2, and MMP-14) | [100] |
| Full-thickness circular excisional wound in nondiabetic and diabetic rats (streptozotocin-induced) | ASCs > untreated controls: rate of wound healing | No significant difference between volume density of collagen and vessel and also length density of vessels in ASC-treated and control groups | [101] |
| Excisional wound healing in normal and diabetic rats (streptozotocin-induced) | Rat ASCs significantly accelerated wound closure in normal and diabetic rat, including increased epithelialization and granulation tissue deposition | Increased VEGF, HGF, and FGF-2 protein expression in ASC-treated wounds, as compared with control and fibroblast-treated wounds | [102] |
| Full-thickness excision wound in diabetic (NOD/SCID; streptozotocin-induced) mice | Human ASC < human AM-MSCs: promotion of wound healing, reepithelialization, and cellularity | Human ASC < human amnion-derived MSCs: mRNA and protein expression of angiogenic factors (IGF-1, EGF, and IL-8) | [104] |
| Full-thickness excision wound in mice | Human ASC > BM-MSCs > AM-MSCs > untreated control: promotion of wound healing, reepithelialization, and granulation tissue | Human ASC > AM-MSCs and BM-MSCs > control: promotion of human DF migration. hDFs cocultured with ASC significantly upregulated the mRNA expression of VEGF, bFGF, KGF, and TGF-β | [105] |
| Full-thickness skin graft model in diabetic rats (induced by streptozotocin) | Autologous rat ASCs increased survival, angiogenesis, and epithelialization; reduced necrosis, as compared with untreated controls | ASCs increased VEGF and TGF-β3 expression in epidermis-dermis and graft-bed fascial area as compared with controls | [106] |
| Full-thickness wound made by biopsy punch in normal and diabetic (dbdb) mice | Mouse normal ASCs > mouse diabetic ASCs: wound healing rate; reepithelization and keratinocyte proliferation; granulation tissue formation; dermal regeneration | ND | [107] |
| Full-thickness wound in diabetic rats (streptozotocin-induced) | Rat ASCs accelerated wound healing as compared with diabetic rats without ASC treatment; reduced periwound inflammation; promoted cell proliferation | Rat ASCs increased the expression of EGF and VEGF in fibroblasts and endothelial cells at the wound margin | [115] |
| Radiation wounds | |||
| Radiation-induced skin ulcer in rats | Rat ASCs promoted a faster rate of wound healing and increased neovascularization and granulation tissue as compared with untreated controls | ND | [112] |
| Burn wounds | |||
| Partial-thickness scald injury in mice | Mouse ASCs alone or combined fat isografts and ASCs determined significantly decreased wound depth compared to fat isografts and untreated controls | ASCs alone or fat isograft with ASCs determined a significant reduction in apoptosis and increased vascularization by immunohistochemistry when compared to fat alone and controls | [110] |
| Full-thickness burn wounds in athymic mice created by thermal injury | No effect on wound healing time between ASC-treated and untreated cases; increased vascularity in ASC-treated mice | Increased type I collagen and type III collagen, and markers of adipogenesis (FABP-4, PPARγ) in the ASC-treated group by RT-PCR analysis | [111] |
| Surgical wounds | |||
| Full-thickness wound in rabbits | Autologous ASC inoculation induced a more rapid and more complete wound-healing process when compared with autologous BM-MSCs and allogeneic ASCs | ASC-treated wounds exhibited better regeneration of epithelial layers, collagen deposition, and PCNA-positive nuclei in epithelial regenerated epidermis compared to BM-MSC treated lesions | [113] |
| Full-thickness wound in mice | Clusters (speroids) of hASCs with low-level light therapy (LLLT) groups accelerated wound closure, including neovascularization and regeneration of skin appendages, compared with the other groups (cluster or LLLT) | hASC cluster was CD31+, CD34+, and KDR+. At the level of wound bed, greater amount of growth factors were observed in the cluster+LLLT group than in the control groups | [116, 117] |
AM-MSCs: amniotic membrane-derived mesenchymal stem cells; ASCs: adipose-derived stem cells; bFGF: basic fibroblast growth factor; BM-MSCs: bone marrow-derived mesenchymal stem cells; EGF: epidermal growth factor; FABP: Fatty Acid Binding Protein; HGF: hepatocyte growth factor; IGF: insulin-like growth factor; IL: interleukin; KGF: keratinocyte growth factor; MMP: matrix metalloproteinase; PCNA: Proliferating Cell Nuclear Antigen; PPAR: peroxisome proliferator-activated receptor; TGF: transforming growth factor; VEGF: vascular endothelial growth factor.